Cell Biochemistry and Biophysics

, Volume 40, Issue 1, pp 1–80 | Cite as

Adult reserve stem cells and their potential for tissue engineering

  • Henry E. Young
  • Cecile Duplaa
  • Marina Romero-Ramos
  • Marie-Francoise Chesselet
  • Patrick Vourc'h
  • Michael J. Yost
  • Kurt Ericson
  • Louis Terracio
  • Takayuki Asahara
  • Haruchika Masuda
  • Sayaka Tamura-Ninomiya
  • Kristina Detmer
  • Robert A. Bray
  • Timothy A. Steele
  • Douglas Hixson
  • Mohammad el-Kalay
  • Brain W. Tobin
  • Roy D. Russ
  • Michael N. Horst
  • Julie A. Floyd
  • Nicholas L. Henson
  • Kristina C. Hawkins
  • Jaime Groom
  • Amar Parikh
  • Lisa Blake
  • Laura J. Bland
  • Angela J. Thompson
  • Amy Kirincich
  • Catherine Moreau
  • John Hudson
  • Frank P. BowyerIII
  • T. J. Lin
  • Asa C. BlackJr.
Original Article


Tissue restoration is the process whereby multiple damaged cell types are replaced to restore the histoarchitecture and function to the tissue. Several theories, have been proposed to explain the phenomenon of tissue restoration in amphibians and in animals belonging to higher order. These theories include dedifferentiation of damaged tissues, transdifferentiation of lineage-committed progenitor cells, and activation of reserve, precursor cells. Studies by Young et al. and others demonstrated that connective tissue compartments throughout postnatal individuals contain reserve precursor cells. Subsequent repetitive single cell-cloning and cell-sorting studies revealed that these reserve precursor cells consisted of multiple populations of cells, including, tissue-specific progenitor cells, germ-layer lineage stem cells, and pluripotent stem cells. Tissue-specific progenitor cells display various capacities for differentiation, ranging from unipotency (forming a single cell type) to multipotency (forming multiple cell types). However, all progenitor cells demonstrate a finite life span of 50 to 70 population doublings before programmed cell senescence and cell death occurs. Germ-layer lineage stem cells can form a wider range of cell types than a progenitor cell. An individual germ-layer lineage stem cell can form all cells types within its respective germ-layer lineage (i.e., ectoderm, mesoderm, or endoderm). Pluripotent stem cells can form a wider range of cell types than a single germ-layer lineage stem cell. A single pluripotent stem cell can form cells belonging to all three germ layer lineages. Both germ-layer lineage stem cells and pluripotent stem cells exhibit extended capabilities for self-renewal, far surpassing the limited life span of progenitor cells (50–70 population doublings). The authors propose that the activation of quiescent tissue-specific progenitor cells, germ-layer lineage stem cells, and/or pluripotent stem cells may be a potential explanation, along with dedifferentiation and transdifferentiation, for the process of tissue restoration. Several model systems are currently being investigated to determine the possibilities of using these adult quiescent reserve precursor cells for tissue engineering.

Index Entries

Adult pluripotent stem cells mammals humans embyonic mesenchymal neurodegenerative diabetes infarction 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Toole, B. P., and Gross, J. (1971) The extracellular matrix of the regenerating newt limb: synthesis and removal of hyaluronate prior to differentiation. Dev. Biol. 25, 57–77.PubMedCrossRefGoogle Scholar
  2. 2.
    Stocum, D. L. (1998) Regenerative biology and engineering: strategies for tissue restoration. Wound Rep. Reg. 6, 276–290.CrossRefGoogle Scholar
  3. 3.
    Tsai R. Y., Kittappa, R., and McKay, R. G. D. (2002) Plasticity, niches, and the use of stem cells. Dev. Cell 2, 707–712.PubMedCrossRefGoogle Scholar
  4. 4.
    Donovan, P. J., and Gearhart, J. (2001) The end of the beginning for pluripotent stem cells. Nature 414, 92–97.PubMedCrossRefGoogle Scholar
  5. 5.
    Forbes, S. J., Vig, P., Poulsom, R., Wright, N. A., and Alison, M. R. (2002) Adult stem cell plasticity: new pathways of tissue regeneration become visible. Clin. Sci. (Lond.) 103, 355–369.Google Scholar
  6. 6.
    Poulsom, R., Alison, M. R., Forbes, S. J., and Wright, N. A. (2002) Adult stem cell plasticity. J. Pathol. 197, 441–456.PubMedCrossRefGoogle Scholar
  7. 7.
    Eglitis, M. A., and Mezey, E. (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc. Natl. Acad. Sci. USA 94, 4080–4085.PubMedCrossRefGoogle Scholar
  8. 8.
    Brazelton, T. R., Rossi, F. M., Keshet, G. I., and Blau, H. M. (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290, 1775–1779.PubMedCrossRefGoogle Scholar
  9. 9.
    Woodbury, D., Schwarz, E. J., Prockop, D. J., and Black, I. B. (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61, 364–370.PubMedCrossRefGoogle Scholar
  10. 10.
    Petersen, B. E., Bowen, W. C., Patrene, K. D., Mars, W. M., Sullivan, A. K., Murase, N., et al. (1999) Bone marrow as a potential source of hepatic oval cells. Science 284, 1168–1170.PubMedCrossRefGoogle Scholar
  11. 11.
    Lagasse, E., Connors, H., Al-Dhalimy, M., Reitsma, M., Dohse, M., Osborne, L., et al. (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med. 6, 1229–1234.PubMedCrossRefGoogle Scholar
  12. 12.
    Theise, N. D., Badger, S., Serena, R., Henegariu, O., Sell, S., Crawford, J. M., et al. (2000) Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 31, 235–240.PubMedCrossRefGoogle Scholar
  13. 13.
    Ferrari, G., Cusella-De Angelis, G., Coletta, M., Paolucci, E., Stornaiuolo A., Cossu, G., et al. (1998) Muscle regeneration by bone marrowderived myogenic progenitors. Science 279, 1528–1530.PubMedCrossRefGoogle Scholar
  14. 14.
    Gussoni, E., Soneoka, Y., Strickland, C. D., Buzney, E. A., Khan, M. K., Flint, A. F., et al. (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401, 390–394.PubMedGoogle Scholar
  15. 15.
    Bjornson, C. R., Rietze, R. L., Reynolds, B. A., Magli, M. C., and Vescovi, A. L. (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283, 534–537.PubMedCrossRefGoogle Scholar
  16. 16.
    Vescovi, A. L., Galli, R., and Gritti, A. (2001) The neural stem cells and their transdifferentiation capacity. Biomed. Pharmacother. 55, 201–205.PubMedCrossRefGoogle Scholar
  17. 17.
    Clarke, D. L., Johansson, C. B., Wilbertz, J., Veress, B., Nilsson, E., Karlstrom, H., et al. (2000) Generalized potential of adult neural stem cells. Science 288, 1660–1663.PubMedCrossRefGoogle Scholar
  18. 18.
    Galli, R., Borello, U., Gritti, A., Minasi, M. G., Bjornson, C., Coletta, M., et al. (2000) Skeletal myogenic potential of human and mouse neural stem cells. Nat. Neurosci. 3, 986–991.PubMedCrossRefGoogle Scholar
  19. 19.
    Tsai, R. Y., and McKay, R. D. (2000) Cell contact regulates fate choice by cortical stem cells. J. Neurosci. 20, 3725–3735.PubMedGoogle Scholar
  20. 20.
    Jackson, K. A., Mi, T., and Goodell, M. A. (1999) Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc. Natl. Acad. Sci. USA 96, 14482–14486.PubMedCrossRefGoogle Scholar
  21. 21.
    Bjerknes, M., and Cheng, H. (2002) Multipotential stem cells in adult mouse gastric epithelium. Am. J. Physiol. Gastrointest. Liver Physiol. 283, G767-G777.PubMedGoogle Scholar
  22. 22.
    Grounds, M. D., Garrett, K. L., Lai, M. C., Wright, W. E., and Beilharz, M. W. (1992) Identification of muscle precursor cells in vivo by use of MyoD1 and myogenin probes. Cell. Tiss. Res. 267, 99–104.CrossRefGoogle Scholar
  23. 23.
    Beauchamp, J. R., Heslop, L., Yu, D. S. W., Tajbakhsh, S., Kelly, R. G., Wernig, A., et al. (2000) Expresiion of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J. Cell. Biol. 151, 1221–1233.PubMedCrossRefGoogle Scholar
  24. 24.
    Young, H. E. (1977) Epidermal ridge formation during limb regeneration in the adult salamander, Ambystoma annulatum. Proc. Ark. Acad. Sci. 31, 107–109.Google Scholar
  25. 25.
    Young, H. E. (1977) Limb regeneration in the adult salamander, Ambystoma annulatum Cope 1889 (Amphibia: Ambystomatidae). Fayetteville: University of Arkansas Library Press.Google Scholar
  26. 26.
    Young H. E. (1977) Anomalies during limb regeneration in the adult salamander, Ambystoma annulatum. Proc. Ark. Acad. Sci. 31, 110–111.Google Scholar
  27. 27.
    Young, H. E. (1983) A Temporal Examination of Glycoconjugates During the Initiation Phase of Limb Regeneration in Adult Ambystoma. Texas Tech University Library Press, Lubbock, TX.Google Scholar
  28. 28.
    Young, H. E. (2000) Stem cells and tissue engineering. In Gene Therapy in Orthopaedic and Sports Medicine (Huard, J., Fu, F. H., eds.), Springer-Verlag, New York, pp. 143–173.Google Scholar
  29. 29.
    Young, H. E. (2004) Existence of reserve quiescent stem cells in adults, from amphibians to humans. Curr. Top. Microbiol. Immunol. 280, 71–109.PubMedGoogle Scholar
  30. 30.
    Young, H. E. and Lucas, P. A. (1998) Pluripotent mesenchymal stem cells and methods of use thereof. US Patent No. 5,827,735.Google Scholar
  31. 31.
    Young, H. E., Bailey, C. F., and Dalley, B. K. (1983) Environmental conditions prerequisite for complete limb, regeneration in the postmetamorphic adult land-phase salamander, Ambystoma. Anat. Rec. 206, 289–294.PubMedCrossRefGoogle Scholar
  32. 32.
    Young, H. E., Bailey, C. F., and Dalley, B. K. (1983) Gross morphological analysis of limb regeneration in postmetamorphic adult Ambystoma. Anat. Rec. 206, 295–306.PubMedCrossRefGoogle Scholar
  33. 33.
    Young, H. E., Dalley, B. K., and Markwald, R. R. (1983) Identification of hyaluronate within peripheral nervous tissue matrices during limb regeneration. In Developing and Regenerating Vertebrate Nervous Systems, Neurology and Neurobiology (Coates, P. W., Markwald, R. R., Kenny, A. D., eds.) Alan R. Liss. New York, vol. 6 pp. 175–183.Google Scholar
  34. 34.
    Young, H. E., Dalley, B. K., and Markwald, R. R. (1983) The interaction of glycosaminoglycans (GAG) and nervous tissue regeneration in adult Ambystoma. Anat. Rec. 205, 202.Google Scholar
  35. 35.
    Young, H. E., Bailey, C. F., Markwald, R. R., and Dalley, B. K. (1985) Histological analysis of limb regeneration in postmetamorphic adult Ambystoma. Anat. Rec. 212, 183–194.PubMedCrossRefGoogle Scholar
  36. 36.
    Young, H. E., Dalley, B. K., and Markwald, R. R. (1989) Glycoconjugates in normal wound tissue matrices during the initiation phase of limb regeneration in adult Ambystoma. Anat. Rec. 223, 231–241.PubMedCrossRefGoogle Scholar
  37. 37.
    Young, H. E., Young, V. E., and Caplan, A. I. (1989) Comparison of fixatives for maximal retention of radiolabeled glycoconjugates for autoradiography, including use of sodium sulfate to release unincorporated [35S]sulfate. J. Histochem. Cytochem. 37, 223–228.PubMedGoogle Scholar
  38. 38.
    Young, H. E., Morrison, D. C., Martin, J. D., and Lucas, P. A. (1991) Cryopreservation of embryonic chick myogenic lineage-committed stem cells. J. Tiss. Cult. Meth. 13, 275–284.CrossRefGoogle Scholar
  39. 39.
    Young, H. E., Ceballos, E. M., Smith, J. C., Lucas, P. A., and Morrison, D. C. (1992) Isolation of embryonic chick myosatellite and pluripotent mesenchymal stem cells. J. Tiss. Cult. Meth. 14, 85–92.CrossRefGoogle Scholar
  40. 40.
    Young, H. E., Sippel, J., Putnam, L. S., Lucas, P. A., and Morrison, D. C. (1992) Enzyme-linked immuno-culture assay. J. Tiss. Cult. Meth. 14, 31–36.CrossRefGoogle Scholar
  41. 41.
    Young, H. E., Ceballos, E. M., Smith, J. C., Mancini, M. L., Wright, R. P., Ragan, B. L., et al. (1993) Pluripotent mesenchymal stem cells reside within avian connective tissue matrices. In Vitro Cell. Dev. Biol. Anim. 29A, 723–736.PubMedGoogle Scholar
  42. 42.
    Young, H. E., Mancini, M. L., Wright, R. P., Smith, J. C., Black, A. C., Jr., Reagan, C. R., et al. (1995) Mesenchymal stem cells reside within the connective tissues of many organs. Dev. Dynam. 202, 137–144.Google Scholar
  43. 43.
    Young, H. E., Wright, R. P., Mancini, M. L., Lucas, P. A., Reagan, C. R., and Black, A. C., Jr. (1998) Bioactive factors affect proliferation and phenotypic expression in pluripotent and progenitor mesenchymal stem cells. Wound Rep. Reg. 6, 65–75.CrossRefGoogle Scholar
  44. 44.
    Young, H. E., Rogers, J. J., Adkison, L. R., Lucas, P. A., and Black, A. C., Jr. (1998) Muscle morphogenetic protein induces myogenic gene expression in Swiss-3T3 cells. Wound Rep. Reg. 6, 530–541.Google Scholar
  45. 45.
    Young, H. E., Steele, T. A., Bray, R. A., Detmer, K., Blake, L. W., Lucas, P. A., et al. (1999) Human pluripotent and progenitor cells display cell surface cluster differentiation markers CD10, CD13, CD56, and MHC Class-I. Proc. Soc. Exp. Biol. Med. 221, 63–71.PubMedCrossRefGoogle Scholar
  46. 46.
    Young, H. E., Duplaa, C., Young, T. M., Floyd, J. A., Reeves, M. L., Davis, K. H., et al. (2001) Clonogenic analysis reveals reserve stem cells in postnatal mammals: I. Pluripotent mesenchymal stem cells. Anat. Rec. 263, 350–360.PubMedCrossRefGoogle Scholar
  47. 47.
    Young, H. E., Steele, T., Bray, R. A., Hudson, J., Floyd, J. A., Hawkins, K. C., et al. (2001) Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat. Rec. 264, 51–62.PubMedCrossRefGoogle Scholar
  48. 48.
    Young, H. E., Black, A. C., Jr. (2004) Adult stem cells. Anat. Rec., 276A, 75–102.CrossRefGoogle Scholar
  49. 49.
    Young, H. E., Duplaa, C., Yost, M. J., Henson, N. L., Floyd, J. A., Detmer, K., et al. (2004) Clonogenic analysis reveals reserve stem cells in postnatal mammals: II. Pluripotent epiblastic-like stem cells. Anat. Rec. 276A, in press.Google Scholar
  50. 50.
    Lucas, P. A., Calcutt, A. F., Ossi, P., Young, H. E., and Southerland, S. S. (1993) Mesenchymal stem cells from granulation tissue. J. Cell. Biochem. 17E, 122.Google Scholar
  51. 51.
    Lucas, P. A., Young, H. E., and Laurencin, C. T. (1994) Muscle morphogenetic protein and use thereof. US Patent No. 5,328,695.Google Scholar
  52. 52.
    Lucas, P. A., Calcutt, A. F., Ossi, P., Young, H. E., and Southerland, S. S. (1994) Granulation tissue contains cells capable of differentiating into multiple mesenchymal phenotypes. J. Cell. Biochem. 18C, 276.Google Scholar
  53. 53.
    Lucas, P. A., Calcutt, A. F., Southerland, S. S., Wilson, J. A., Harvey, R. L., Warejcka, D. J., et al. (1995) A population of cells resident within embryonic and newborn rat skeletal muscle is capable of differentiating into multiple mesodermal phenotypes. Wound Rep. Reg. 3, 457–468.Google Scholar
  54. 54.
    Lucas, P. A., Warejcka, D. J., Zhang, L.-M., Newman, W. H., and Young, H. E. (1996) Effect of rat mesenchymal stem cells on the development of abdominal adhesions after surgery. J. Surg. Res. 62, 229–232.PubMedCrossRefGoogle Scholar
  55. 55.
    Lucas, P. A., Warejcka, D. J., Young, H. E., and Lee, B. Y. (1996) Formation of abdominal adhesions is inhibited by antibodies to transforming growth factor-beta1. J. Surg. Res. 65, 135–138.PubMedCrossRefGoogle Scholar
  56. 56.
    Pate, D. W., Southerland, S. S., Grande, D. A., Young, H. E., and Lucas, P. A. (1993) Isolation and differentiation of mesenchymal stem cells from rabbit muscle. Surg. Forum 44, 587–589.Google Scholar
  57. 57.
    Rogers, J. J., Young, H. E., Adkison, L. R., Lucas, P. A., and Black, A. C., Jr. (1995) Differentiation factors induce expression of muscle, fat, cartilage, and bone in a clone of mouse pluripotent mesenchymal stem cells. Am. Surg 61, 231–236.PubMedGoogle Scholar
  58. 58.
    Dixon, K., Murphy, R. W., Southerland, S. S., Young, H. E., Dalton, M. L., and Lucas, P. A. (1996) Recombinant human bone morphogenetic proteins-2 and 4 (rhBMP-2 and rhBMP-4) induce several mesenchymal phenotypes in culture. Wound Rep. Reg. 4, 374–380.CrossRefGoogle Scholar
  59. 59.
    Warejcka, D. J., Harvey, R., Taylor, B. J., Young, H. E., and Lucas, P. A. (1996) A population of cells isolated from rat heart capable of differentiating into several mesodermal phenotypes. J. Surg. Res. 62, 233–242.PubMedCrossRefGoogle Scholar
  60. 60.
    Romero-Ramos, M., Vourc'h, P., Young, H. E., Lucas, P. A., Wu, Y., Chivatakarn, O., et al. (2002) Neuronal differentiation of stem cells isolated from adult muscle. J. Neurosci. Res. 69, 894–907.PubMedCrossRefGoogle Scholar
  61. 61.
    Thornton, C. S. (1968) Amphibian limb regeneration. In Advances in Morphogenesis (Brachet, J., King, T. J. V., eds.). Academic Press, New York, vol. 7, pp. 205–249.Google Scholar
  62. 62.
    Singer, M. (1978) On the nature of the neurotrophic phenomenon in urodele regeneration. Am. Zool. 18, 829–841.Google Scholar
  63. 63.
    Tank, P. W. and Holder, N. (1981) Pattern regulation in the regenerating limbs of urodele amphibians. Quart Rev Biol 56, 113–142.CrossRefGoogle Scholar
  64. 64.
    Brockes, J. P. (1997) Amphibian limb regeneration: rebuilding a complex structure. Science 276, 81–87.PubMedCrossRefGoogle Scholar
  65. 65.
    Iten, L. E. and Bryant, S. V. (1973) Forelimb regeneration from different levels of amputation in the newt, Notophthalamus viridescens: length, rate, stage. Wilhelm Roux Arch. 173, 77–89.CrossRefGoogle Scholar
  66. 66.
    Farber, J. (1959) An experimental analysis of regional organization in the regenerating forelimb of the axolotl (Ambystoma mexicanum). Arch. Biol. 71, 1–72.Google Scholar
  67. 67.
    Tank, P. W., Carlson, B. M., and Connelly, T. G. (1976) A staging system for forelimb regeneration in the axolotl, Ambystoma mexicanum. J. Morph. 150, 117–128.PubMedCrossRefGoogle Scholar
  68. 68.
    Stocum, D. L. (1979) Stages of forelimb regeneration in Ambystoma maculatum. J. Exp. Zool. 209, 395–416.PubMedCrossRefGoogle Scholar
  69. 69.
    Scadding, S. R. (1977) Phylogenetic distribution of limb regeneration capacity in adult amphibia. J. Exp. Zool. 202, 57–68.CrossRefGoogle Scholar
  70. 70.
    Singer, M. (1951) Induction of regeneration of the forelimb of the frog by augmentation of the nerve supply. Proc. Soc. Exp. Biol. Med. 76, 413–416.PubMedGoogle Scholar
  71. 71.
    Pritchette, W. H. and Dent, J. N. (1972) The role of size in the rate of limb regeneration in the adult newt. Growth 36, 275–289.Google Scholar
  72. 72.
    Young, H. E., Dalley, B. K., and Markwald, R. R. (1989) Effect of selected denervations on glycoconjugate composition and tissue morphology during the initiation phase of limb regeneration in adult Ambystoma. Anat. Rec. 223, 231–241.PubMedCrossRefGoogle Scholar
  73. 73.
    Brockes, J. P. (1997) Amphibian limb regeneration: rebuilding a complex structure. Science 276, 81–87.PubMedCrossRefGoogle Scholar
  74. 74.
    Young, H. E., Carrino, D. A., and Caplan, A. I. (1989) Histochemical analysis of newly synthesized and resident sulfated glycosaminoglycans during musculogenesis in the embryonic chick leg. J. Morphol. 201, 85–103.PubMedCrossRefGoogle Scholar
  75. 75.
    Mauro, A. (1961) Satellite cell of skeletal muscle fibers. J. Biophys. Biochem. Cytol. 9, 493–498.PubMedGoogle Scholar
  76. 76.
    Campion, D. R. (1984) The musce satellite cell: a review. Int. Rev. Cytol. 87, 225–251.PubMedGoogle Scholar
  77. 77.
    Ailhaud, G., Grimaldi, P., and Negrel, R. (1992) Cellular and molecular aspects of adipose tissue development. Annu. Rev. Nutr. 12, 207–233.PubMedCrossRefGoogle Scholar
  78. 78.
    Cruess, R. L. (1982) The Musculoskeletal System: Embryology, Biochemistry, and Physiology. Churchill Livingston, New York.Google Scholar
  79. 79.
    Vierck, J. L., McNamara, J. P., and Dodson, M. V. (1996) Proliferation and differentiation of progeny of ovine unilocular fat cells (adipofibroblasts). In Vitro Cell. Dev. Biol. Anim. 32, 564–572.PubMedGoogle Scholar
  80. 80.
    Owen, M. (1988) Marrow stromal cells. J. Cell. Sci. Suppl. 10, 63–76.PubMedGoogle Scholar
  81. 81.
    Beresford, J. N. (1989) Osteogenic stem cells and the stromal system of bone and marrow. Clin. Orthop. 240, 270–280.PubMedGoogle Scholar
  82. 82.
    Caplan, A. I., Elyaderani, M., Mochizuki, Y., Wakitani, S., and Goldberg, V. (1997) Principles of cartilage repair and regeneration. Clin. Orthop. Rel. Res. 342, 254–269.CrossRefGoogle Scholar
  83. 83.
    Prockop, D. J. (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276, 71–74.PubMedCrossRefGoogle Scholar
  84. 84.
    Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., et al. (1999) Multilineage potential of adult human mesenchymal stem cells. Science 148, 143–147.CrossRefGoogle Scholar
  85. 85.
    Palis, J. and Segel, G. B. (1998) Developmental biology of erythropoiesis. Blood Rev. 12, 1061–1064.CrossRefGoogle Scholar
  86. 86.
    McGuire, W. P. (1998) High-dose chemotherapy and autologous bone marrow or stem cell reconstitution for solid tumors. Curr. Probl. Cancer 22, 135–137.PubMedCrossRefGoogle Scholar
  87. 87.
    Ratajczak, M. Z., Pletcher, C. H., Marlicz, W., Machlinski, B., Moore, J., Wasik, M., et al. (1998) CD34+, kit+, rhodamine 123 (low) phenotype identifies a marrow cell population highly enriched for human hematopoietic stem cells. Leukemia 12, 942–950.PubMedCrossRefGoogle Scholar
  88. 88.
    Hayflick, L. (1965) The limited in vitro lifetime of human diploid cell strains. Exp. Cell. Res. 37, 614–636.PubMedCrossRefGoogle Scholar
  89. 89.
    Young, H. E., Carrino, D. A., and Caplan, A. I. (1990) Changes in synthesis of sulfated glycoconjugates during muscle development, maturation, and aging in embryonic to senescent CBF-1 mouse. Mech. Ageing Dev. 53, 179–193.PubMedCrossRefGoogle Scholar
  90. 90.
    Urist, M. R. (1965) Bone: formation by autoinduction. Science 150, 893–899.PubMedCrossRefGoogle Scholar
  91. 91.
    Hauschka, P. V., Mavrakos, A. E., Iafrati, M. D., Doleman, S. E., and Klagsbrun, M. (1986) Growth factors in bone matrix: isolation of multiple types by affinity chromatography on heparin-Sepharose. J. Biol. Chem. 261, 12665–12674.PubMedGoogle Scholar
  92. 92.
    Linkhart, T. A., Jennings, J. C., Mohan, S., Wakley, G. K., and Baylink, D. J. (1986) Characterization of mitogenic activities extracted from bovine bone matrix. Bone 7(6), 479–487.PubMedCrossRefGoogle Scholar
  93. 93.
    Canalis, E., McCarthy, T., and Centrella, M. (1988) Growth factors and the regulation of bone remodeling. J. Clin. Invest. 81, 277–281.PubMedGoogle Scholar
  94. 94.
    Wozney, J. M., Rosen, V., Celeste, A. J., Mitsock, L. M., Whitters, M. J., Kriz, R. W., et al. (1988) Novel regulators of bone formation: molecular clones and activities. Science 242, 1528–1534.PubMedCrossRefGoogle Scholar
  95. 95.
    Urist, M. R. (1989) Bone morphogenetic protein, bone regeneration, heterotopic ossification, and the bone-bone marrow consortium. In Bone and Mineral Research (Peck, W. A., ed.). Elsevier, New York, vol. 6, pp. 57–112.Google Scholar
  96. 96.
    Wang, E. A., Rozen, V., D'Alessandro, J. S., Bauduy, M., Cordes, P., Harada, T., et al. (1990) Recombinant human bone morphogenetic protein induces bone formation (cartilage induction). Proc. Natl. Acad. Sci. USA 87, 2220–2224.PubMedCrossRefGoogle Scholar
  97. 97.
    Syftestad, G. T., Lucas, P. A., and Caplan, A. I. (1985) The in vitro chondrogenic response of limb-bud mesenchyme to a water-soluble fraction prepared from demineralized bone matrix. Differentiation 29, 230–237.PubMedCrossRefGoogle Scholar
  98. 98.
    Frolik, C. A., Ellis, F., and Williams, C. (1989) Isolation and characterization of insulin-like growth factor-II from human bone. Biochem. Biophys. Res. Commun. 151, 1011–1018.CrossRefGoogle Scholar
  99. 99.
    Lucas, P. A., Young, H. E., and Putnam, L. S. (1991) Quantitation of chondrogenesis in culture using Alcec blue staining. FASEB J. 5, A390.Google Scholar
  100. 100.
    Kishimoto, T., Kikutani, H., Borne, A. E. G. K.r.v.d., Goyert, S. M., Mason, D., Miyasaka, M., et al. (1997) Leucocyte Typing VI: White Cell Differentiation Antigens. Garland, Hamden, CT.Google Scholar
  101. 101.
    Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147.PubMedCrossRefGoogle Scholar
  102. 102.
    Shamblott, M. J., Axelman, J., Wang, S., Bugg, E. M., Littlefield, J. W., Donovan, P. J., et al. (1998) Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc. Natl. Acad. Sci. USA 95, 13726–13731.PubMedCrossRefGoogle Scholar
  103. 103.
    Reyes, M. and Verfaillie, C. M. (2001) Characterization of multipotent adult progenitor cells, a subpopulation of mesenchymal stem cells. Ann. N Y Acad. Sci. 938, 231–233; discussion 233-235.PubMedCrossRefGoogle Scholar
  104. 104.
    Jiang, Y., Vaessen, B., Lenvik, T., Blackstad, M., Reyes, M., and Verfaillie, C. M. (2002) Multipotent progenitor cells can be isolated from bone marrow, muscle and brain. Exp. Hematol. 30, 896–904.PubMedCrossRefGoogle Scholar
  105. 105.
    McKinney-Freeman, S. L., Jackson, K. A., Camargo, F. D., Ferrari, G., Mavillio, F., and Goodell, M. A. (2002) Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc. Natl. Acad. Sci. USA 99, 1341–1346.PubMedCrossRefGoogle Scholar
  106. 106.
    Lucas, P. A., Calcutt, A. F., Mulvaney, D. J., Young, H. E., and Southerland, S. S. (1992) Isolation of putative mesenchymal stem cells from rat embryonic and adult skeletal muscle. In Vitro Cell. Dev. Biol. 28, 154A.Google Scholar
  107. 107.
    Lucas, P. A., Syftestad, G. T., and Caplan, A. I. (1986) Partial isolation and characterization of a chemotactic factor from adult bovine bone for mesenchymal cells. Bone 7, 365–371.PubMedCrossRefGoogle Scholar
  108. 108.
    Lucas, P. A., Price, P. A., and Caplan, A. I. (1988) Chemotactic response of mesenchymal cells, fibroblasts and osteoblast-like cells to bone Gla protein. Bone 5, 19–23.Google Scholar
  109. 109.
    Lucas, P. A., Syftestad, G. T., and Caplan, A. I. (1988) A water-soluble fraction from adult bone stimulates the differentiation of cartilage explants of embryonic muscle. Differentiation 37, 47–52.PubMedCrossRefGoogle Scholar
  110. 110.
    Lucas, P. A., Syftestad, G. T., Goldberg, V. M., and Caplan, A. I. (1989) Ectopic induction of cartilage and bone by water-soluble proteins from bovine bone using a collagenous delivery vehicle. Biomed. Mater. Res. 23(A, Suppl. 1), 23–39.CrossRefGoogle Scholar
  111. 111.
    Lucas, P. A., Laurencin, C., Syftestad, G. T., Domb, A., Goldberg, V. M., Caplan, A. I., et al. (1990) Ectopic induction of cartilage and bone by water-soluble proteins from bovine bone using a polyanhydride delivery vehicle. J. Biomed. Mater. Res. 24, 901–911.PubMedCrossRefGoogle Scholar
  112. 112.
    Lucas, P. A. and Dziewiatkowski, D. D. (1987) Feedback control of selected biosynthetic activities of chondrocytes in culture. Connec. Tiss. Res. 16, 323–341.Google Scholar
  113. 113.
    Lucas, P. A. and Caplan, A. I. (1988) Chemotactic response of embryonic limb bud mesenchymal cells and muscle-derived fibroblasts to transforming growth factor-beta. Connec. Tiss. Res. 18, 1–7.Google Scholar
  114. 114.
    Lucas, P. A. (1989) Chemotactic response of osteoblast-like cells to transforming growth factor-beta. Bone 10, 459–463.PubMedCrossRefGoogle Scholar
  115. 115.
    Bowerman, S. G., Taylor, S. S., Putnam, L., Young, H. E., and Lucas, P. A. (1991) Transforming growth factor-β (TGF-β) stimulates chondrogenesis in cultured embryonic mesenchymal cells. Surg. Forum 42, 535–536.Google Scholar
  116. 116.
    Shoptaw, J. H., Bowerman, S., Yong, H. E., and Lucas, P. A. (1991) Use of gelfoam as a substrate for osteogenic cells of marrow. Surg. Forum 42, 535–538.Google Scholar
  117. 117.
    Hinton, J. L., Jr., Warejcka, D. J., Mei, Y., McLendon R. E., Laurencin, C., Lucas, P. A., et al. (1995) Inhibition of epidural scar formation after lumbar laminectomy in the rat. Spine 20, 564–570; discussion 579-580.PubMedCrossRefGoogle Scholar
  118. 118.
    Reynolds, B. A., and Weiss, S. (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707–1710.PubMedCrossRefGoogle Scholar
  119. 119.
    Gage, F. H., Coates, P. W., Palmer, T. D., Kuhn, H. G., Fisher, L. J., Suhonen, J. O., et al. (1995) Survival and differentiation of adult neuronal progenitr cells transplanted to the adult brain. Proc. Natl. Acad. Sci. USA 92, 11897–11883.CrossRefGoogle Scholar
  120. 120.
    Bjorklund, A. and Lindvall, O. (2000) Cell replacement therapies for central nervous system disorders. Nat. Neurosci. 3, 537–544.PubMedCrossRefGoogle Scholar
  121. 121.
    Cornellison, D. D. and Wold, B. J. (1997) Singlecell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells. Dev. Biol. 191, 270–283.CrossRefGoogle Scholar
  122. 122.
    Bosch, P., Musgrave, D. S., Lee, J. Y., Cummins, J., Shuler, T., Ghivizzani, T. C., et al. (2000) Osteoprogenitor cells within skeletal muscle. J. Orthop. Res. 18, 933–944.PubMedCrossRefGoogle Scholar
  123. 123.
    Lee, J. Y., Qu-Petersen, Z., Cao, B., Kimura, S., Jankowski, R., Cummins, J., et al. (2000) Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J. Cell. Biol. 150, 1085–1100.PubMedCrossRefGoogle Scholar
  124. 124.
    Toma, J. G., Akhavan, M., Fermandes, K. J., Barnabe-Heider, F., Sadikot, A., Kaplan, D. R., et al. (2001) Isolation of multipotent stem cells from the dermis of mammalian skin. Nat. Cell. Biol. 3, 778–784.PubMedCrossRefGoogle Scholar
  125. 125.
    Azizi, S. A., Stokes, D., Augelli, B. J., DiGirolamo, C., and Prockop, D. J. (1998) Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats-similarities to astrocyte grafts. Proc. Natl. Acad. Sci. USA 95, 3908–3913.PubMedCrossRefGoogle Scholar
  126. 126.
    Kopen, G. C., Prockop, D. J., and Phinney, D. G. (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc. Natl. Acad. Sci. USA 96, 10711–10716.PubMedCrossRefGoogle Scholar
  127. 127.
    Mezey, E., Chandross, K. J., Harta, G., Maki, R. A., and McKercher, S. R. (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290, 1779–1782.PubMedCrossRefGoogle Scholar
  128. 128.
    Sanchez-Ramos, J., Song, S., Cardozo-Pelaez, F., Hazzi, C., Stedeford, T., Willing, A., et al. (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp. Neurol. 164, 247–256.PubMedCrossRefGoogle Scholar
  129. 129.
    Colter, D. C., Sekiya, I., and Prockop, D. J. (2001) Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc. Natl. Acad. Sci. USA 98, 7841–7845.PubMedCrossRefGoogle Scholar
  130. 130.
    Deng, W., Obrocka, M., Fischer, I., and Prockop, D. J. (2001) In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem. Biophys. Res. Commun. 282, 148–152.PubMedCrossRefGoogle Scholar
  131. 131.
    Reyes, M., Lund, T., Lenvik, T., Aguiar, D., Koodie, L., and Verfaillie, C. M. (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98, 2615–2625.PubMedCrossRefGoogle Scholar
  132. 132.
    Reynolds, B. A., Tetzlaff, W., and Weiss, S. (1992). A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J. Neurosci. 12, 4565–4574.PubMedGoogle Scholar
  133. 133.
    Svendsen, C. N., ter Borg, M. G., Armstrong, R. J., Rosser, A. E., Chandran, S., Ostenfeld, T., et al. (1998) A new method for the rapid and long term growth of human neural precursor cells. J. Neurosci. Methods 85, 141–152.PubMedCrossRefGoogle Scholar
  134. 134.
    Cochard, P. and Paulin, D. (1984) Initial expression of neurofilaments and vimentin in the central and peripheral nervous system of the mouse embryo in vivo. J. Neurosci. 4, 2080–2094.PubMedGoogle Scholar
  135. 135.
    Lendahl, U., Zimmerman, L. B., and McKay, R. D. (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60, 585–595.PubMedCrossRefGoogle Scholar
  136. 136.
    Zimmerman, L., Parr, B., Lendahl, U., Cunningham, M., McKay, R., Gavin, B., et al. (1994) Independent regulatory elemtns in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12, 11–24.PubMedCrossRefGoogle Scholar
  137. 137.
    Feldman, D. H., Thinschmidt, J. S., Peel, A. L., Papke, R. L., and Reier, P. J. (1996) Differentiation of ionic currents in CNS progentior cells: dependence upon substrate attachment and epidermal growth factor. J. Exp. Neurol. 140, 206–217CrossRefGoogle Scholar
  138. 138.
    Dawson, M. R., Levine, J. M., and Reynolds, R. (2000) NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J. Neurosci. Res. 61, 471–479.PubMedCrossRefGoogle Scholar
  139. 139.
    Gritti, A., Galli, R., and Vescovi, A. L. (2001) Cultures of stem cells of the central nervous system. In Protocols for Neural Cell Culture (Fedoroff, S., Richardson, A., eds.), Totowa, NJ, Humana Press, pp. 173–198.CrossRefGoogle Scholar
  140. 140.
    van Praag, H., Schinder, A. E., Christie, B. R., Toni, N., Palmer, T. D., and Gage, F. H. (2002) Functional neurogenesis in the adult hippocampus. Nature 415, 1030–1034.PubMedCrossRefGoogle Scholar
  141. 141.
    Pesce, M. and Scholer, H. R. (2001) Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 19, 271–278.PubMedCrossRefGoogle Scholar
  142. 142.
    Mansouri, A., Hallonet, M., and Gruss, P. (1996) Pax genes and their roles in cell differ-entiation and development. Curr. Opin. Cell. Biol. 8, 851–857.PubMedCrossRefGoogle Scholar
  143. 143.
    Orkin, S. H. and Zon, L. I. (2002) Hematopoiesis and stem cells: plasticity versus developmental heterogeneity. Nat. Immunol. 3, 323–328.PubMedCrossRefGoogle Scholar
  144. 144.
    Mertelsmann, R. (2000) Plasticity of bone marrow-derived stem cells. J. Hematother. Stem Cell Res. 9, 957–960.PubMedCrossRefGoogle Scholar
  145. 145.
    Alexander, W. S. (1998) Cytokines in hematopoiesis. Int. Rev. Immunol. 16, 651–682.PubMedGoogle Scholar
  146. 146.
    National Blood Data Resource Center ( Scholar
  147. 147.
    Slavin, S. (2000) New strategies for bone marrow transplantation. Curr. Opin. Immunol. 12, 542–551.PubMedCrossRefGoogle Scholar
  148. 148.
    National Marrow Donor Program ( Scholar
  149. 149.
    Confer, D. L. (1997) Unrelated marrow donor registries. Curr. Opin. Hematol. 4, 408–412.PubMedCrossRefGoogle Scholar
  150. 150.
    van der Kooy, D. and Weiss, S. (2000) Why stem cells? Science 287, 1439–1441.PubMedCrossRefGoogle Scholar
  151. 151.
    Weissman, I. L. (2000) Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 287, 1442–1446.PubMedCrossRefGoogle Scholar
  152. 152.
    Vogel, G. (2000) Cell biology: stem cells: new excitement, persistent questions. Science 290, 1672–1674.PubMedCrossRefGoogle Scholar
  153. 153.
    Alison, M. R., Poulsom, R., Jeffery, R., Dhillon, A. P., Quaglia, A., Jacob, J., et al. (2000) Hepatocytes from non-hepatic adults stem cells. Nature 406, 257.PubMedCrossRefGoogle Scholar
  154. 154.
    Li, F., Linton, G. F., Sekhsaria, S., Whiting-Theobald, N., Katkin, J. P., Gallin, J. I., et al. (1994) CD34+ peripheral blood progenitors as a target for genetic correction of the two flavocytochrome b558 defective forms of chronic granulomatous disease. Blood 84, 53–58.PubMedGoogle Scholar
  155. 155.
    Eisenbarth G. S., Connelly, J., and Soeldner, J. S. (1987) The “natural” history of Type I diabetes. Diabetes/Metabolism Rev. 3, 873–891.Google Scholar
  156. 156.
    Ward, W. K., Beard, J. C., and Porte, D., Jr. (1986) Clinical aspects of islet b-cell function in non-insulin dependent diabetes mellitus. Diabetes/Metabolism Rev. 2, 297–313.CrossRefGoogle Scholar
  157. 157.
    Chandra, R. K. (1989) Nutritional regulation of immunity and risk of infection in old age. Immunology 67, 141–147.PubMedGoogle Scholar
  158. 158.
    Fiatarone, M. A., Marks, E.C., Ryan, N. D., Meridith, C. N., Lipsitz, L. A., and Evans, W. J. (1990) High-intensity strength training in nonagenarians: effects on skeletal muscle. JAMA 263, 3029–3034.PubMedCrossRefGoogle Scholar
  159. 159.
    Frontera, W. R., Hughes, V. A., Lutz, K. J., and Evans, W. J. (1991) A cross-sectional study of muscle strength and mass in 45- to 78 yr-old men and women. J. Appl. Physiol 71, 644–650.PubMedGoogle Scholar
  160. 160.
    Walsh, C. H., Soler, N. G., James, H, Harvey, T. C., Thomas, B. J., Fremlin, J. H., et al. (1976) Studies in whole body potassium and whole body nitrogen in newly diagnosed diabetics. Q. J. Med. 45(178), 295–301.PubMedGoogle Scholar
  161. 161.
    Nair, K. S., Garrow, J. S., Ford, C., Mahler, R. F., and Halliday, D. (1983), Effect of poor diabetic control and obesity on whole body protein metabolism in man. Diabetologia 25, 400–403.PubMedCrossRefGoogle Scholar
  162. 162.
    Morgan, H. E., Jefferson, L. S., Wolpert, E. B., and Rannels, D. E. (1971) Regulation of protein synthesis in heart muscle: II. Effect of amino acid levels and insulin on ribosomal aggregation. J. Biol. Chem. 246, 2163–2170.PubMedGoogle Scholar
  163. 163.
    Jefferson, L. S., Li, J. B., and Rannels, S. R. (1977) Regulation by insulin of amino acid release and protein turnover in the perfused rat hemicorpus. J. Biol. Chem. 252, 1476–1483.PubMedGoogle Scholar
  164. 164.
    Peavy, D. E., Taylor, J. M., and Jefferson, L. S. (1978) Correlation of albumin production rates and mRNA levels in livers of normal, diabetic and insulin-treated diabetic rats. Proc. Natl. Acad. Sci. USA 75, 5879–5883.PubMedCrossRefGoogle Scholar
  165. 165.
    Froesch, E. R., Guler, H. P., Schmid, C., Ernst, M., and Zapf, J. (1990) Insulin-like growth factors. In Ellenberg and Rifkin's Diabetes Mellitus: Theory and Practice (Rifkin, H., Porte, D., eds.). Elsevier, New York, pp. 154–169.Google Scholar
  166. 166.
    Lemozy, S., Pucilowska, L. B., and Underwood, L. E. (1994) Reduction of insulin-like growth factor-1 (IGF-1) in protein-restricted rats is associated with differential regulation of IGF-binding protein messenger ribonucleic acids in liver and kidney, and peptides in liver and serum. Endocrinology 135, 617–623PubMedCrossRefGoogle Scholar
  167. 167.
    Straus, D. S. (1994) Nutritional regulation of hormones and growth factors that control mammalian growth FASEB J. 8, 6–12.PubMedGoogle Scholar
  168. 168.
    Tobin, B. W., Lewis, J. T., Chen, Z., Tobin, B. L. and Finegood, D. T. (1995) Insulin action in a model of graded insulin secretion using islet transplanted rats. Transplantation 59, 1–6.Google Scholar
  169. 169.
    Tobin, B. W., Lewis, J. T., Tobin, B. L. and Finegood, D. T. (1995) Insulin action in previously diabetic rats receiving graded numbers of islets of Langerhans. Transplantation 59, 1464–1470.PubMedGoogle Scholar
  170. 170.
    Tobin, B. W. and Marchello, M. J. (1995) Islet transplantation reverses carcass protein loss in diabetic rats without inducing disproportionate fat accumulation. diabetologia 38, 881–888.PubMedGoogle Scholar
  171. 171.
    Tobin, B. W., Welch-Holland, K. R., and Marchello, M. J. (1997) Pancreatic islet transplantation improves body composition, decreases food intake and normalizes feed efficiency in previously diabetic female rats. J. Nutr. 127, 1191–1197.PubMedGoogle Scholar
  172. 172.
    Weir, G. C. and Bonner-Weir, S. (1998) Islet transplantation as a treatment for diabetes. J. Am. Optom. Assoc. 69, 727–732.PubMedGoogle Scholar
  173. 173.
    Shapiro, A. M. J., Lakey, J. R. T., Ryan, E. A., Korbutt, G. S., Toth, E., Warnock, G. L., et al. (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N. Engl. J. Med. 343, 230–237.PubMedCrossRefGoogle Scholar
  174. 174.
    Shapiro, A. M. J., Ryan, E. A., and Lakey, J. R. T. (2001) Pancreatic islet transplantation in the treatment of diabetes mellitus. Best Practice Res. Clin. Endocrin. Metab. 15, 241–264.CrossRefGoogle Scholar
  175. 175.
    Shapiro, A. M. J. and Lakey, J. R. T. (2000) Future trends in islet transplantation. Diabetes Tech. Ther. 2, 449–452.CrossRefGoogle Scholar
  176. 176.
    Ryan, E. A., Lakey, J. R. T., and Shapiro, A. M. J. (2001) Clinical results after islet transplantation. J. Invest. Med. 49, 559–562.Google Scholar
  177. 177.
    Ryan, E. A., Lakey, J. R. T., Rajotte, R. V., Korbutt, G. S., Kin, T., Imes, S., et al. (2001) Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes 50, 710–719.PubMedCrossRefGoogle Scholar
  178. 178.
    Cornelius, J. G., Tchernev, V., Kao, K. J., and Peck, A. B. (1997) In vitro-generation of islets in long-term cultures of pluripotent stem cells from adult mouse pancreas. Horm. Metab. Res. 29(6), 271–277.PubMedCrossRefGoogle Scholar
  179. 179.
    Ramiya, V. K., Maraist, M., Arfos, K. E., Schatz, D. A., Peck, A. B., and Cornelius, J. G. (2000) Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat. Med. 6(3), 278–282.PubMedCrossRefGoogle Scholar
  180. 180.
    Bonner-Weir, S., Taneja, M., Weir, G. C., Tatarkiewicz, K., Song, K.-H., Sharma, A., et al. (2000) In vitro cultivation of human islets from expanded ductal tissue. Proc. Natl. Acad. Sci. USA 97, 7999–8004.PubMedCrossRefGoogle Scholar
  181. 181.
    Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R., and McKay, R. (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292, 1389–1393.PubMedCrossRefGoogle Scholar
  182. 182.
    Soria, B., Roche, E., Berna, G., Leon-Quinto, T., Reig, J. A., and Martin, F. (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49, 157–162.PubMedCrossRefGoogle Scholar
  183. 183.
    Soria, B., Skoudy, A., and Martin, F. (2001) From stem cells to beta cells: new strategies in cell therapy of diabetes mellitus. Diabetologia 4, 407–415.CrossRefGoogle Scholar
  184. 184.
    Assady, S., Maor, G., Amit, M., Itskovitz-Eldor, J., Skorecki, K. L., and Tzukerman, M. (2001) Insulin production by human embryonic stem cells. Diabetes 50, 1691–1697.PubMedCrossRefGoogle Scholar
  185. 185.
    Mankin, H. J. (1982) The response of articular cartilage to mechanical injury. J. Bone Joint Surg. Am. 64, 460–466.PubMedGoogle Scholar
  186. 186.
    McDermott, A. G., Langer, F., Pritzker, K. P., and Gross, A. E. (1985) Fresh small-fragment osteochondral allografts: long-term follow-up study on first 100 cases. Clin. Orthop. 197, 96–102.PubMedGoogle Scholar
  187. 187.
    Chesterman P. J. and Smith, A. U. (1968) Homotransplantation of articular cartilage and isolated chondrocytes: an experimental study in rabbits. J. Bone Joint Surg. Br. 50, 184–197.PubMedGoogle Scholar
  188. 188.
    Bentley, G. and Greer, R. B., III, (1971) Homotransplantation of isolated epiphyseal and articular cartilage chondrocytes into joint surfaces of rabbits. Nature 230, 385–388.PubMedCrossRefGoogle Scholar
  189. 189.
    Green, W. T. (1977) Articular cartilage repair: behavior of rabbit chondrocytes during tissue culture and subsequent allografting. Clin. Orthop. 124, 237–250.PubMedGoogle Scholar
  190. 190.
    Moskalewski, S. (1991) Transplantation of isolated chondrocytes. Clin. Orthop. 272, 16–20.PubMedGoogle Scholar
  191. 191.
    Wakitani, S., Kimura, T., Hirooka, A., Ochi, T., Yoneda, M., Yasui, N., et al. (1989) Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. J. Bone Joint Surg. Br. 71, 74–80.PubMedGoogle Scholar
  192. 192.
    Kawabe, N. and Yoshinato, M. (1991) The repair of full thickness articular cartilage defects: immune responses to reparative tissue formed by allogeneic growth plate chondrocytes. Clin. Orthop. 268, 279–293.PubMedGoogle Scholar
  193. 193.
    Matsusue, Y., Yamamuro, T., and Hama, H. (1993) Arthroscopic multiple osteochondral transplantation to the chondral defect in the knee associated with anterior cruciate ligament disruption. Arthroscopy 9, 318–321.PubMedCrossRefGoogle Scholar
  194. 194.
    Garret, J. C. (1986) Treatment of osteochondral defects of the distal femur with fresh osteochondral allografts: a preliminary report. Arthroscopy 2, 222–226.CrossRefGoogle Scholar
  195. 195.
    Skoog, T. and Johansson, S. H. (1976) The formation of articular cartilage from free perichondrial grafts. Plast. Reconstr. Surg. 57(1), 1–6.PubMedCrossRefGoogle Scholar
  196. 196.
    Homminga, G. N., Bulstra, S. K., Bouwmeester, P. S., and van der Linden, A. J. (1990) Perichondral grafting for cartilage lesions of the knee. J. Bone Joint Surg. Br. 72, 1003–1007.PubMedGoogle Scholar
  197. 197.
    Rubak, J. M. (1982) Reconstruction of articular cartilage defects with free periosteal grafts: an experimental study. Acta. Orthop. Scand. 53, 175–80.PubMedCrossRefGoogle Scholar
  198. 198.
    O'Driscoll, S. W., Keeley, F. W., and Salter, R. B. (1988) Durability of regenerated articular cartilage produced by free autogenous periosteal grafts in major full-thickness defects in joint surfaces under the influence of continuous passive motion: a follow-up report at one year. J. Bone Joint Surg. Am. 70, 595–606.PubMedGoogle Scholar
  199. 199.
    Ritsila, V. A., Santavirta, S., Alhopuro, S., Poussa, M., Jaroma, H., Rubak, J. M., et al. (1994) Periosteal and perichondral grafting in reconstructive surgery. Clin. Orthop. 302, 259–265.PubMedGoogle Scholar
  200. 200.
    Caplan, A. I. (1991) Mesenchymal stem cells. J. Orthop. Res. 9, 641–650.PubMedCrossRefGoogle Scholar
  201. 201.
    Minas, T. and Neher, S. (1997) Current concepts in the treatment of articular cartilage defects. Orthopedics 20, 525–538.PubMedGoogle Scholar
  202. 202.
    Grande, D. A., Pitman, M. I., Peterson, L., Menche, D., and Klein, M. (1989) The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J. Orthop. Res. 7, 208–218.PubMedCrossRefGoogle Scholar
  203. 203.
    Brittberg, M., Lindahl, A., Nilsson, A., Ohlsson, C., Isaksson, O., and Peterson, L. (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N. Engl. J. Med. 331, 889–895.PubMedCrossRefGoogle Scholar
  204. 204.
    Brittberg, M., Nilsson, A., Lindahl, A., Ohlsson, C., and Peterson, L. (1996) Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin. Orthop. 326, 270–283.PubMedCrossRefGoogle Scholar
  205. 205.
    Frenkel, S. R., Toolan, B., Menche, D., Pitman, M. I., and Pachence, J. M. (1997) Chondrocyte transplantation using a collagen bilayer matrix for cartilage repair. J. Bone Joint Surg. Br. 79, 831–836.PubMedCrossRefGoogle Scholar
  206. 206.
    Wakitani, S., Goto, T., Pineda, S. J., Young, R. G. Mansour, J. M., Caplan, A. I., et al. (1994) Mesenchymal cell-based repair of large, fullthickness defects of articular cartilage. J. Bone Joint Surg. Am. 76, 579–592.PubMedGoogle Scholar
  207. 207.
    Breinan, H. A., Minas, T., Hsu, H.-P., Nehrer, S., Sledge, C. B., and Spector, M. (1997) Effect of cultured autologous chondrocytes on repair of chondral defects in a canine model. J. Bone Joint Surg. Am. 79, 1439–1451.PubMedGoogle Scholar
  208. 208.
    Kolettas, E., Buluwela, L., Bayliss, M. T., and Muir, H. I. (1995) Expression of cartilage-specific molecules is retained on long-term culture of human articular chondrocytes. J. Cell. Sci. 108, 1991–1999.PubMedGoogle Scholar
  209. 209.
    Grande, D. A., Southerland, S. S., Manji, R., Pate, D. W., Schwartz, R. E., and Lucas, P. A. (1995) Repair of articular cartilage defect using mesenchymal stem cells. Tiss. Eng. 1, 345–353.CrossRefGoogle Scholar
  210. 210.
    Syftestad, G. T. and Caplan, A. I. (1984) A fraction from extracts of demineralized adult bone stimulates the conversion of mesenchymal cells into chondrocytes. Dev. Biol. 104, 348–356.PubMedCrossRefGoogle Scholar
  211. 211.
    Sato, S., Rahemtulla, F., Prince, C. W., Tomana, M., and Butler, W. T. (1985) Acidic glycoproteins from bovine compact bone. Connect. Tiss. Res. 14(1), 51–64.Google Scholar
  212. 212.
    Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(259), 680–685.PubMedCrossRefGoogle Scholar
  213. 213.
    Roberts, R. M., Baumbach, G. A., Buhi, W. C., Denny, J. B., Fitzgerald, L. A., Babelyn, S. F., and Horst, M. N. (1984) Analysis of membrane polypeptides by two-dimensional polyacrylamide gel electrophoresis. In: Molecular and Chemical Characterization of Membrane Receptors (Venter, J., ed.), Alan R. Liss, New York, pp. 61–113.Google Scholar
  214. 214.
    Ewton, D. Z. and Florini, J. R. (1981) Effects of somatomedins and insulin on myoblast differentiation in vitro. Dev. Biol. 86, 31–39.PubMedCrossRefGoogle Scholar
  215. 215.
    Florini, J. R., Roberts, A. B., Ewton, D. Z., Falen, S. L., Flanders, K. C., and Sporn, M. B. (1986) Transforming growth factor-beta: a very potent inhibitor of myoblast differentiation, identical to the differentiation inhibitor secreted by Buffalo rat liver cells. J. Biol. Chem. 261, 16509–16513.PubMedGoogle Scholar
  216. 216.
    Florini, J. R., Ewton, D. Z., Falen, S. L., and Van Wyck, J. J. (1986) Biphasic concentration dependency of stimulation of myoblast differentiation by somatomedins. Am. J. Physiol. 250, C771-C778.PubMedGoogle Scholar
  217. 217.
    Florini, J. R. and Magri, K. A. (1989) Effects of growth factors on myogenic differentiation. Am. J. Physiol. 256, C701-C711.PubMedGoogle Scholar
  218. 218.
    Sejersen, T., Betscholtz, C., Sjolund, M., Heldin, C. H., Estermark, B., and Thyberg, J. (1986) Rat skeletal myoblasts and arterial smooth muscle cells express the gene for the A chain but not the gene for the B chain (c-sis) of platelet-derived growth factor (PDGF) and produce a PDGF-like protein. Proc. Natl. Acad. Sci. USA 83, 6844–6848.PubMedCrossRefGoogle Scholar
  219. 219.
    Ewton, D. Z., Falen, S. L., and Florini, J. R. (1987) The type-II insulin-like growth factor (IGF) receptor has low affinity for IGF-I analogs: pleiotypic actions of the IGFs on myoblasts are apparently mediated by the type-I receptor. Endocrinology 120, 115–123.PubMedCrossRefGoogle Scholar
  220. 220.
    Allbrook, D. (1981) Skeletal muscle regeneration. Muscle Nerve 4, 234–245.PubMedCrossRefGoogle Scholar
  221. 221.
    Carlson, B. M. (1973) The regeneration of skeletal muscle: a review. Am. J. Anat. 137, 119–149.PubMedCrossRefGoogle Scholar
  222. 222.
    Carlson, B. M. (1979) Relationship between tissue and epimorphic regeneration of skeletal muscle. In: Muscle Regeneration (Mauro, A., ed.). Raven, New York, p. 57.Google Scholar
  223. 223.
    Carlson, B. M. (1986) Regeneration of entire skeletal muscles. Fed. Proc. 45, 1456–1460.PubMedGoogle Scholar
  224. 224.
    Carlson, B. M. and Faulkner, J. A. (1983) The regeneration of skeletal muscle fibers following injury: a review. Med. Sci. Sports Exerc. 15, 187–198.PubMedCrossRefGoogle Scholar
  225. 225.
    Faulkner, J. A. and Carlson, B. M. (1986) Skeletal muscle regeneration: a historical perspective. Fed. Proc. 45, 1454–1455.PubMedGoogle Scholar
  226. 226.
    Donovan, C. M. and Faulkner, J. A. (1987) Plasticity of skeletal muscle: regenerating fibers adapt more rapidly than surviving fibers. J. Appl. Physiol. 62, 2507–2511.PubMedGoogle Scholar
  227. 227.
    Schoen, F. J. (1999) The heart. In: Pathological Basis of Disease, 6th ed., Cotran, R., Kumar, V., and Collins, T. eds.), W. B. Saunders, Philadelphia, pp. 543–599.Google Scholar
  228. 228.
    Chiu, R. C.-J. (2001) Theraputic cardiac angiogenesis and myogenesis: the promises and challenges on a new frontier. J. Thorac. Cardiovasc. Surg. 122(5), 851–852.PubMedCrossRefGoogle Scholar
  229. 229.
    Marelli, D., Desrosiers, C., El-Alfy, M., Kao, R. L., and Chiu, R. C. (1992) Cell transplantation for myocardial repair: an experimental approach. Cell. Transplant. 1, 383–390.PubMedGoogle Scholar
  230. 230.
    Taylor, D. A., Atkins, B. Z., Hungspreugs, P., Jones, T. R., Reedy, M. C., Hutchenson, K. A., et al. (1997) Delivery of primary autologous skeletal myoblasts into rabbit heart by coronary infusion: a potential approach to myocardial repair. Proc. Assoc. Am. Physicians 109, 245–253.PubMedGoogle Scholar
  231. 231.
    Koh, G. Y., Soonpaa, M. H., Klug, M. G., and Field, L. (1993) Long-term survival of AT-1 cardiomyocyte grafts in syngenic myocardium. Am. J. Physiol. 264 (Heart Circ. Physiol. 33), H1727-H1733.PubMedGoogle Scholar
  232. 232.
    Soonpaa, M. H., Koh, G. Y., Klug, M. G., and Field, L. G. (1994) Formation of nascent intercalated disks between grafted cardiomyocytes and host myocardium. Science 264, 98–101.PubMedCrossRefGoogle Scholar
  233. 233.
    Klung, M., Soonpaa, M., Koh, G., and Field, L. (1996) Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J. Clin. Invest. 98, 216–224.CrossRefGoogle Scholar
  234. 234.
    Taylor, D. A., Atkins, B. Z., Hungspreugs, P., Jones, T. R., Reddy, M. C., Hutcheson, K. A., et al. (1998) Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat. Med. 4(8), 929–933.PubMedCrossRefGoogle Scholar
  235. 235.
    Sakai, T., Li, R.-K., Weisel, R. D., Mickle, D. A., Kim, E.-J., Tomita, S., et al. (1999) Autologous heart cell transplantation improves function after myocardial injury. Ann. Thorac. Surg. 68, 2074–2081.PubMedCrossRefGoogle Scholar
  236. 236.
    Li, R.-K., Weisel, R. D., Mickle, D. A., Jia, Z.-Q., Kim, E. J., Sakai, T., et al. (2000) Autologous porcine heart cell transplantation improved heart function after a myocardial infarction. J. Thorac. Cardiovasc. Surg. 119, 62–68.PubMedCrossRefGoogle Scholar
  237. 237.
    Reincke, H., Zhang, M., Bartosek, T., and Murry, C. E. (1999) Survival integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation 100, 193–202.Google Scholar
  238. 238.
    Weksler, B., Ng, B., Lenert, J., and Burt, M. (1994) A simplified method for endotracheal intubation in the rat. J. Appl. Physiol. 76(4), 1823–1825.PubMedGoogle Scholar
  239. 239.
    Price, R. L. Chintanowonges, C., Shiraishi, I., Borg, T. K., and Terracio, L. (1996) Local and regional variations in myofibrillar patterns in looping rat hearts. Anat. Rec. 245, 83.PubMedCrossRefGoogle Scholar
  240. 240.
    Couffinhal, T., Kearney, M., Sullivan, A., Silver, M., Tsurumi, Y., and Isner, J. M. (1997) Histochemical staining following LacZ gene transfert underestimates transfection efficiency. Hum. Gene Ther. 8, 929–934.PubMedGoogle Scholar
  241. 241.
    Saito, T., Dennis, J. E., Lennon, D. P., Young, R. G., and Caplan, A. I. (1995) Myogenic expression of mesenchymal stem cells within myotubes of mdx mice in vitro and in vivo. Tiss. Eng. 1, 327–343.CrossRefGoogle Scholar
  242. 242.
    Deasy, B. M., Jankowski, R. J., and Huard, J. (2001) Muscle-derived stem cells: characterization and potential for cell-mediated therapy. Blood Cells Mol. Dis. 27, 924–933.PubMedCrossRefGoogle Scholar
  243. 243.
    Jankowski, R. J., Haluszczak, C., Trucco, M., and Kuard, J. (2001) Flow cytometric characterization of myogenic cell populations obtained via the preplate technique: potential for rapid isolation of muscle-derived stem cells. Hum. Gene Ther. 12, 619–628.PubMedCrossRefGoogle Scholar
  244. 244.
    Dent, C. L. and Latchman, D. S. (1993) DNA mobility shift assays. In Transcription Factors: A Practical Approach (Latchman, D.S., ed.). Oxford University Press, New York, pp. 1–26.Google Scholar
  245. 245.
    Callaerts, P., Halder, G., and Gehring, W. J. (1997) PAX-6 in development and evolution. Annu. Rev. Neurosci. 20, 483–532.PubMedCrossRefGoogle Scholar
  246. 246.
    Vitalis, T., Cases, O., Engelkamp, D., Verney, C., and Price, D. J. (2000) Defect of tyrosine hydroxylase-immunoreactive neurons in the brains of mice lacking the transcription factor Pax6. J. Neurosci. 20, 6501–6516.PubMedGoogle Scholar
  247. 247.
    Mastick, G. S. and Andrews, G. L. (2001) Pax6 regulates the identity of embryonic diencephalic neurons. Mol. Cell. Neurosci. 17, 190–207.PubMedCrossRefGoogle Scholar
  248. 248.
    Wright, W. E., Binder, M., and Funk, W. (1991) Cyclic Amplification Selection of Targets (CASTing) for the myogenin consensus binding site. Mol. Cell. Biol 11, 4104–4110.PubMedGoogle Scholar
  249. 249.
    Kraus, B. and Pette, D. (1997) Quantification of MyoD, myogenin, MRF4 and Id-1 by reverse transcriptase polymerase chain reaction in rat muscles: effects of hypothyroidism and chronic low-frequency stimulation. Eur. J. Biochem. 247, 98–106.PubMedCrossRefGoogle Scholar
  250. 250.
    Skalli, O., Ropraz, P., Trzeciak, A., Benzonana, G., Gillessen, D., and Gabbiani, G. (1986) A monoclonal antibody against α-smooth muscle actin: a new probe for smooth muscle differentiation. J. Cell. Biol. 103, 2787–2796.PubMedCrossRefGoogle Scholar
  251. 251.
    Alexander, J. E., Hunt, D. F., Lee, M. K., Shabanowitz, J., Michel, H., Berlin, S. C., et al. (1991) Characterization of posttranslational modifications in neuron-specific class III β-tubulin by mass spectrometry. PNAS 88, 4685–4689.PubMedCrossRefGoogle Scholar
  252. 252.
    Dotti, C. G., Banker, G. A., and Binder, L. I. (1987) The expression and distribution of the microtubule-associated proteins tau and microtubule-associated protein 2 in hippocampal neurons in the rat in situ and in cell culture. Neuroscience 1, 121–130.CrossRefGoogle Scholar
  253. 253.
    Debus, E., Weber, K., and Osborn, M. (1983) Monoclonal antibodies specific for glial fibrillary acidic (GFA) protein and for each of the neurofilament triplet polypeptides. Differentiation 25, 193–203.PubMedCrossRefGoogle Scholar
  254. 254.
    Shaw, G., Osborn, M., and Weber, K. (1986) Reactivity of a panel of neurofilament antibodies on phosphorylated and dephosphorylated neurofilaments. Eur. J. Cell. Biol. 42, 1–9.PubMedGoogle Scholar
  255. 255.
    Beck, K. D., Powell-Braxton, L., Widmer, H.-R., Valverde, J., and Hefti, F. (1995) Igf1 Gene disruption results in reduced brain size, CNS, hypomyleination and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron 14, 717–730.PubMedCrossRefGoogle Scholar
  256. 256.
    Justicia, C., Gabriel, C., and Planas, A. M. (2000) Activation of the JAK/STAT pathway following transient focal cerebral ischemia: signaling through Jak 1 and Stat 3 in astrocytes. Glia 30, 253–270.PubMedCrossRefGoogle Scholar
  257. 257.
    Zhang, S. C. (2001) Defining glial cells during CNS development. Nat. Rev. Neurosci. 2, 840–843.PubMedCrossRefGoogle Scholar
  258. 258.
    Spinkle, T. J., Agee, J. F., Tippins, R. B., Chamberlain, C. R., Faguet, G. B., and DeVries, G. H. (1987) Monoclonal antibody production to human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powder and conservation of sequence between CNP1 and CNP2. Brain Res. 426, 349–357.CrossRefGoogle Scholar
  259. 259.
    Asahara, T., Kalka, C., and Isner, J. M. (2000) Stem cell therapy and gene transfer for regeneration. Gene Ther. 7, 451–457.PubMedCrossRefGoogle Scholar
  260. 260.
    Kalka, C., Masuda, H., Takahashi, T., Kalka-Moll, W. M., Silver, M., Kearney, M., et al. (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc. Natl. Acad. Sci. USA 97, 3422–3427.PubMedCrossRefGoogle Scholar
  261. 261.
    Masuda, H., Kalka, C., and Asahara, T. (2000) Endothelial progenitor cells for regeneration. Hum. Cell. 13, 153–160.PubMedGoogle Scholar
  262. 262.
    Murayama, T., Tepper, O. M., Silver, M., Ma, H., Losordo, D. W., Isner, J. M., et al. (2002) Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp. Hematol. 8, 967–972.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Henry E. Young
    • 1
    • 2
  • Cecile Duplaa
    • 5
  • Marina Romero-Ramos
    • 6
  • Marie-Francoise Chesselet
    • 6
  • Patrick Vourc'h
    • 6
  • Michael J. Yost
    • 7
  • Kurt Ericson
    • 7
  • Louis Terracio
    • 8
  • Takayuki Asahara
    • 9
    • 10
  • Haruchika Masuda
    • 9
    • 10
  • Sayaka Tamura-Ninomiya
    • 9
    • 10
  • Kristina Detmer
    • 1
  • Robert A. Bray
    • 11
  • Timothy A. Steele
    • 12
  • Douglas Hixson
    • 13
  • Mohammad el-Kalay
    • 14
  • Brain W. Tobin
    • 1
    • 2
  • Roy D. Russ
    • 1
  • Michael N. Horst
    • 1
  • Julie A. Floyd
    • 1
  • Nicholas L. Henson
    • 1
  • Kristina C. Hawkins
    • 1
  • Jaime Groom
    • 1
  • Amar Parikh
    • 1
  • Lisa Blake
    • 1
  • Laura J. Bland
    • 1
  • Angela J. Thompson
    • 1
  • Amy Kirincich
    • 7
  • Catherine Moreau
    • 5
  • John Hudson
    • 4
  • Frank P. BowyerIII
    • 2
  • T. J. Lin
    • 3
  • Asa C. BlackJr.
    • 1
    • 3
  1. 1.Division of Basic Medical SciencesMercer University School of MedicineMacon
  2. 2.Department of PediatricsMercer University School of MedicineMacon
  3. 3.Department of Obstetrics and GynecologyMercer University School of MedicineMacon
  4. 4.Department of Internal MedicineMercer University School of MedicineMacon
  5. 5.INSERM U441France
  6. 6.Department of Neurology, UCLA School of MedicineReed Neurological Research CenterLos Angeles
  7. 7.Department of SurgeryUniversity of South Carolina School of MedicineColumbia
  8. 8.New York University College of DentistryNew York
  9. 9.Cardiovascular Research and Medicine, Tufts University School of MedicineElizabeth's Medical CenterBoston
  10. 10.Kobe Institute of Biomedical Research and Innovation/RIKEN Center of Developmental Biology, ChuoKobeJapan
  11. 11.Department of Pathology and Laboratory MedicineEmory University HospitalAtlanta
  12. 12.Des Moines University-Osteopathic Medical CenterDes Moines
  13. 13.Department of MedicineBrown UniversityProvidence
  14. 14.MorphoGen Pharmaceuticals, Inc.San Diego

Personalised recommendations