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Therapeutic Applications of Mesenchymal Stem/Multipotent Stromal Cells

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Stem Cells & Regenerative Medicine

Abstract

Stem cell therapies offer enormous hope for treating many tragic diseases and tissue defects. In particular, mesenchymal stem/multipotent stromal cells (MSCs) are capable of differentiating into multiple types of connective tissues (i.e., bone, cartilage, and even muscle and neuron) and have proangiogeneic and immunomodulatory effects. MSCs have potential utility for treating a variety of diseases and disorders, including graft versus host disease, problems related to organ transplantation, cardiovascular disease, brain and spinal cord injury, lung, liver, and kidney diseases, and skeletal injuries. This chapter summarizes the current status of therapeutic applications of MSCs. It begins by introducing the basics of MSCs and then focuses on their therapeutic potential, including mechanism of action, delivery routes, MSC homing, the current status of clinical trials, and potential challenges and safety issues. Finally, the chapter describes chemical approaches developed in the authors’ laboratory to promote homing and engraftment of systemically infused MSCs within specific tissues.

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References

  1. Friedenstein, A.J., Chailakhyan, R.K., Latsinik, N.V., et al. (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 17, 331–340.

    Article  PubMed  CAS  Google Scholar 

  2. Eaves, C.J., Cashman, J.D., Sutherland, H.J., et al. (1991) Molecular Analysis of Primitive Hematopoietic Cell Proliferation Control Mechanism. Ann. New York Acad. Sci. 628, 298–306.

    Article  CAS  Google Scholar 

  3. Valtieri, M. and Sorrentino, A. (2008) The mesenchymal stromal cell contribution to homeostasis. J. Cell. Physiol. 217, 296–300.

    Article  PubMed  CAS  Google Scholar 

  4. Caplan, A.I. (1991) Mesenchymal stem cells. J. Orthop. Res. 9, 641–650.

    Article  PubMed  CAS  Google Scholar 

  5. Pittenger, M.F., Mackay, A.M., Beck, S.C., et al. (1999) Multilineage Potential of Adult Human Mesenchymal Stem Cells. Science. 284, 143–147.

    Article  PubMed  CAS  Google Scholar 

  6. Dominici, M., Le Blanc, K., Mueller, I., et al. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 8, 315–317.

    Article  PubMed  CAS  Google Scholar 

  7. Prockop, D.J. (2009) Repair of Tissues by Adult Stem/Progenitor Cells (MSCs): Controversies, Myths, and Changing Paradigms. Mol. Ther. 17, 939–946.

    Article  PubMed  CAS  Google Scholar 

  8. Zuk, P.A., Zhu, M., Mizuno, H., et al. (2001) Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies. Tissue Eng. 7, 211–228.

    Article  PubMed  CAS  Google Scholar 

  9. Williams, J.T., Southeland, S.S., Souza, J., et al. (1999) Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am. Surg. 65, 22–26.

    PubMed  CAS  Google Scholar 

  10. Campagnoli, C., Roberts, I.A.G., Kumar, S., et al. (2001) Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 98, 2396–2402.

    Article  PubMed  CAS  Google Scholar 

  11. Fan, C.G., Tang, F.W., Zhang, Q.J., et al. (2005) Characterization and Neural Differentiation of Fetal Lung Mesenchymal Stem Cells. Cell Transplant. 14, 311–321.

    Article  PubMed  Google Scholar 

  12. Noort, W.A., Kruisselbrink, A.B., In’t Anker, PS., et al. (2002) Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34+ cells in NOD/SCID mice. Exp. Hematol. 30, 870–878.

    Article  PubMed  Google Scholar 

  13. Sarugaser, R., Lickorish, D., Baksh, D., et al. (2005) Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 23, 220–229.

    Article  PubMed  Google Scholar 

  14. In’t Anker, P.S., Scherjon, S.A., Kleijburg-van der Keur, C., et al. (2003) Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood. 102, 1548–1549

    Article  Google Scholar 

  15. Phinney, D.G. and Prockop, D.J. (2007) Concise Review: Mesenchymal Stem/Multipotent Stromal Cells: The State of Transdifferentiation and Modes of Tissue Repair - Current Views. Stem Cells. 25, 2896–2902.

    Article  PubMed  Google Scholar 

  16. Barry, F.P. and Murphy, J.M. (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int. J. Biochem. Cell. Biol. 36, 568–584.

    Article  PubMed  CAS  Google Scholar 

  17. Gucciardo, L., Lories, R., Ochsenbein-Kölble, N., et al. (2009) Fetal mesenchymal stem cells: isolation, properties and potential use in perinatology and regenerative medicine. BJOG 116, 166–172.

    Article  PubMed  CAS  Google Scholar 

  18. Gronthos, S., Zannettino, A.C.W., Hay, S.J., et al. (2003) Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J. Cell Sci. 116, 1827–1835.

    Article  PubMed  CAS  Google Scholar 

  19. Quirici, N., Soligo, D., Bossolasco, P., et al. (2002) Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Exp. Hematol. 30, 783–791.

    Article  PubMed  CAS  Google Scholar 

  20. Guo, K.T., SchÄfer, R., Paul, A., et al. (2006) A New Technique for the Isolation and Surface Immobilization of Mesenchymal Stem Cells from Whole Bone Marrow Using High-Specific DNA Aptamers. Stem Cells. 24, 2220–2231.

    Article  PubMed  CAS  Google Scholar 

  21. Abdallah, B.M. and Kassem, M. (2007) Human mesenchymal stem cells: from basic biology to clinical applications. Gene Ther. 15, 109–116.

    Article  PubMed  CAS  Google Scholar 

  22. Prockop, D.J., Bunnell, B.A. and Phinney, D.G. (2008) Mesenchymal Stem Cells: Methods and Protocols. Meth. Mol. Biol.

    Google Scholar 

  23. Chamberlain, G., Fox, J.M., Ashton, B.A., et al. (2007) Concise Review: Mesenchymal Stem Cells: Their Phenotype, Differentiation Capacity, Immunological Features, and Potential for Homing. Stem Cells. 25, 2739–2749.

    Article  PubMed  CAS  Google Scholar 

  24. García-Castro, J., Trigueros, C., Madrenas, J., et al. (2008) Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool. J. Cell. Mol. Med. 12, 2552–2565.

    Article  PubMed  Google Scholar 

  25. Tyndall, A., Walker, U., Cope, A., et al. (2007) Immunomodulatory properties of mesenchymal stem cells: a review based on an interdisciplinary meeting held at the Kennedy Institute of Rheumatology Division, London, UK, 31 October 2005. Arthritis Res. Ther. 9, 301.

    Article  PubMed  Google Scholar 

  26. Schuleri, K.H., Boyle, A.J. and Hare, J.M. (2007) Mesenchymal stem cells for cardiac regenerative therapy. Handbook Exp. Pharmacol. 180, 195–218.

    Article  CAS  Google Scholar 

  27. Roufosse, C.A., Direkze, N.C., Otto, W.R., et al. (2004) Circulating mesenchymal stem cells. Int. J. Biochem. Cell. Biol. 36, 585–597.

    Article  PubMed  CAS  Google Scholar 

  28. Krampera, M., Pasini, A., Pizzolo, G., et al. (2006) Regenerative and immunomodulatory potential of mesenchymal stem cells. Curr. Op.Pharmacol. 6, 435–441.

    Article  CAS  Google Scholar 

  29. Deans, R.J. and Moseley, A.B. (2000) Mesenchymal stem cells: Biology and potential clinical uses. Exp. Hematol. 28, 875–88.

    Article  PubMed  CAS  Google Scholar 

  30. Kolf, C., Cho, E. and Tuan, R. (2007) Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res. Ther. 9, 204.

    Article  PubMed  CAS  Google Scholar 

  31. Lee, R.H., Pulin, A.A., Seo, M.J., et al. (2009) Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6. Cell Stem Cell. 5, 54–6.

    Article  PubMed  CAS  Google Scholar 

  32. Lee, R.H., Seo, M.J., Pulin, A.A., et al. (2009) The CD34-like protein PODXL and {alpha}6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood. 113, 816–826.

    Article  PubMed  CAS  Google Scholar 

  33. Hara, M., Murakami, T. and Kobayashi, E. (2008) In vivo bioimaging using photogenic rats: Fate of injected bone marrow-derived mesenchymal stromal cells. J. Autoimmun. 30, 163–171.

    Article  PubMed  Google Scholar 

  34. López Ponte, A., Marais, E., Gallay, N., et al. (2007) The In Vitro Migration Capacity of Human Bone Marrow Mesenchymal Stem Cells: Comparison of Chemokine and Growth Factor Chemotactic Activities. Stem Cells. 25, 1737–1745.

    Article  CAS  Google Scholar 

  35. Prockop, D.J. (1997) Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues. Science. 276, 71–74.

    Article  PubMed  CAS  Google Scholar 

  36. Muguruma, Y., Yahata, T., Miyatake, H., et al. (2006) Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood. 107, 1878–1887.

    Article  PubMed  CAS  Google Scholar 

  37. Kraus, K.H. and Kirker-Head, C. (2006) Mesenchymal stem cells and bone regeneration. Vet. Surg. 35, 232–242.

    Article  PubMed  Google Scholar 

  38. Nesselmann, C., Ma, N., Karen Bieback et al. (2008) Mesenchymal stem cells and cardiac repair. J. Cell. Mol. Med. 12, 1795–1810.

    Article  PubMed  CAS  Google Scholar 

  39. Krampera, M., Pizzolo, G., Aprili, G., et al. (2006) Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone. 39, 678–683.

    Article  PubMed  CAS  Google Scholar 

  40. Mao, J. (2005) Stem-cell-driven regeneration of synovial joints. Biol. Cell. 97, 289–301.

    Article  PubMed  CAS  Google Scholar 

  41. Arthur, A., Zannettino, A. and Gronthos, S. (2009) The therapeutic applications of multipotential mesenchymal/stromal stem cells in skeletal tissue repair. J. Cell. Physiol. 218, 237–245.

    Article  PubMed  CAS  Google Scholar 

  42. Gronthos, S., Akintoye, S.O., Cun-Yu Wang et al. (2006) Bone marrow stromal stem cells for Tissue Eng. Periodontology 2000. 41,188–195.

    Article  PubMed  Google Scholar 

  43. Petite, H., Viateau, V., Bensaid, W., et al. (2000) Tissue-engineered bone regeneration. Nat. Biotech. 18, 959–963.

    Article  CAS  Google Scholar 

  44. Ponticiello, M.S., Schinagl, R.M., Kadiyala, S., et al. (2000) Gelatin-based resorbable sponge as a carrier matrix for human mesenchymal stem cells in cartilage regeneration therapy. J. Biomed. Mater. Res. 52, 246–255.

    Article  PubMed  CAS  Google Scholar 

  45. Helmlinger, G., Yuan, F., Dellian, M., et al. (1997) Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat. Med. 3, 177–82.

    Article  PubMed  CAS  Google Scholar 

  46. Psaltis, P.J., Zannettino, A.C.W., Worthley, S.G., et al. (2008) Concise Review: Mesenchymal Stromal Cells: Potential for Cardiovascular Repair. Stem Cells. 26, 2201–2210.

    Article  PubMed  Google Scholar 

  47. Silva, G.V., Litovsky, S., Assad, J.A.R., et al. (2005) Mesenchymal Stem Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Canine Chronic Ischemia Model. Circulation. 111, 150–156.

    Article  PubMed  CAS  Google Scholar 

  48. 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.

    Article  PubMed  CAS  Google Scholar 

  49. Rose, R.A., Jiang, H., Xinghua Wang et al. (2008) Bone Marrow-Derived Mesenchymal Stromal Cells Express Cardiac-Specific Markers, Retain the Stromal Phenotype, and Do Not Become Functional Cardiomyocytes In Vitro. Stem Cells. 26, 2884–2892.

    Article  PubMed  CAS  Google Scholar 

  50. Pijnappels, D.A., Schalij, M.J., Ramkisoensing, A.A., et al. (2008) Forced Alignment of Mesenchymal Stem Cells Undergoing Cardiomyogenic Differentiation Affects Functional Integration With Cardiomyocyte Cultures. Circ. Res. 103, 167–176.

    Article  PubMed  CAS  Google Scholar 

  51. Spitkovsky, D. and Hescheler, J. (2008) Adult mesenchymal stromal stem cells for therapeutic applications. Minim. Invasive. Ther. Allied Tech. 17, 79–902.

    Article  CAS  Google Scholar 

  52. Alvarez-Dolado, M., Pardal, R., Garcia-Verdugo, J.M., et al. (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature. 425, 968–997.

    Article  PubMed  CAS  Google Scholar 

  53. Wang, X.J. and Li, Q.P. (2007) The roles of mesenchymal stem cells (MSCs) therapy in ischemic heart diseases. Biochem. Biophys. Res. Comm. 359, 189–193.

    Article  PubMed  CAS  Google Scholar 

  54. Fox, J.M., Chamberlain, G., Ashton, B.A., et al. (2007) Recent advances into the understan ding of mesenchymal stem cell trafficking. Br. J. Haematol. 137, 491–502.

    Article  PubMed  CAS  Google Scholar 

  55. Uccelli, A., Pistoia, V. and Moretta, L. (2007) Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol. 28, 219–226.

    Article  PubMed  CAS  Google Scholar 

  56. Humphreys, B.D. and Bonventre, J.V. (2008) Mesenchymal Stem Cells in Acute Kidney Injury. Annu. Rev. Med. 59, 311–325.

    Article  PubMed  CAS  Google Scholar 

  57. Angelopoulou, M., Novelli, E., Grove, J.E., et al. (2003) Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice. Exp. Hematol. 31, 413–420.

    Article  PubMed  CAS  Google Scholar 

  58. Kim, D.W., Chung, Y.J., Kim, T.G. et al. (2004) Cotransplantation of third-party mesenchymal stromal cells can alleviate single-donor predominance and increase engraftment from double cord transplantation. Blood. 103, 1941–1948.

    Article  PubMed  CAS  Google Scholar 

  59. Gruber, R., Kandler, B., Holzmann, P., et al. (2005) Bone Marrow Stromal Cells Can Provide a Local Environment That Favors Migration and Formation of Tubular Structures of Endothelial Cells. Tissue Eng. 11, 896–903.

    Article  PubMed  CAS  Google Scholar 

  60. Jones, B.J. and McTaggart, S.J. (2008) Immunosuppression by mesenchymal stromal cells: From culture to clinic. Exp. Hematol. 36, 733–741.

    Article  PubMed  CAS  Google Scholar 

  61. Crop, M., Baan, C., Weimar, W., et al. (2009) Potential of mesenchymal stem cells as immune therapy in solid-organ transplantation. Transpl. Int. 22, 365–376.

    Article  PubMed  CAS  Google Scholar 

  62. Nauta, A.J. and Fibbe, W.E. (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood. 110, 3499–3506.

    Article  PubMed  CAS  Google Scholar 

  63. Abdi, R., Fiorina, P., Adra, C.N., et al. (2008) Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes. 57, 1759–1767.

    Article  PubMed  CAS  Google Scholar 

  64. English, K., Ryan, J.M., Tobin, L., et al. (2009) Cell contact, prostaglandin E and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25 High forkhead box P3+ regulatory T cells. Clin. Exp. Immunol. 156, 149–160.

    Article  PubMed  CAS  Google Scholar 

  65. Reiser, J., Zhang, X.Y., Hemenway, C.S., et al. (2005) Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases. Expert Opin. Biol. Ther. 5, 1571–1584.

    Article  PubMed  CAS  Google Scholar 

  66. Studeny, M., Marini, F.C., Dembinski, J.L., et al. (2004) Mesenchymal Stem Cells: Potential Precursors for Tumor Stroma and Targeted-Delivery Vehicles for Anticancer Agents. J. Natl. Cancer Inst. 96, 1593–1603.

    Article  PubMed  CAS  Google Scholar 

  67. Aboody, K.S., Najbauer, J. and Danks, M.K. (2008) Stem and progenitor cell-mediated tumor selective gene therapy. Gene Ther. 15, 739–752.

    Article  PubMed  CAS  Google Scholar 

  68. Ozawa, K., Sato, K., Oh, I., et al. (2008) Cell and gene therapy using mesenchymal stem cells (MSCs). J. Autoimmun. 30, 121–127.

    Article  PubMed  CAS  Google Scholar 

  69. Karussis, D., Kassis, I., Kurkalli, B.G.S., et al. (2008) Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): A proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases. J. Neurol. Sci. 265, 131–135.

    Article  PubMed  CAS  Google Scholar 

  70. Hurwitz, D.R., Kirchgesser, M., Merrill, W., et al. (1997) Systemic Delivery of Human Growth Hormone or Human Factor IX in Dogs by Reintroduced Genetically Modified Autologous Bone Marrow Stromal Cells. Hum. Gene. Ther. 8, 137–156.

    Article  PubMed  CAS  Google Scholar 

  71. Sasportas, L.S., Kasmieh, R., Wakimoto, H., et al. (2009) Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc. Natl. Acad. Sci. USA. 106, 4822–4827.

    Article  PubMed  Google Scholar 

  72. Karussis, D. and Kassis, I. (2008) The potential use of stem cells in multiple sclerosis: An overview of the preclinical experience. Clin. Neurol. Neurosurg. 110, 889–896.

    Article  PubMed  Google Scholar 

  73. Le Blanc, K., Tammik, C., Rosendahl, K., et al. (2003) HLA expression and immunologic properties of differentiatied and undifferentiated mesenchymal stem cells. Exp. Hematol. 31, 890–896.

    Article  PubMed  CAS  Google Scholar 

  74. Tse, W.T., Pendleton, J.D., Beyer, W.M., et al. (2003) Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation. 75, 389–397.

    Article  PubMed  CAS  Google Scholar 

  75. Karp, J.M. and Teo, G. (2009) Mesenchymal Stem Cell Homing: The Devil Is in the Details. Cell Stem Cell. 4, 206–216.

    Article  PubMed  CAS  Google Scholar 

  76. Spaeth, E., Klopp, A., Dembinski, J., et al. (2008) Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther. 15, 730–738.

    Article  PubMed  CAS  Google Scholar 

  77. Penna, C., Raimondo, S., Ronchi, G., et al. (2008) Early homing of adult mesenchymal stem cells in normal and infarcted isolated beating hearts. J. Cell. Mol. Med. 12, 507–521.

    Article  PubMed  Google Scholar 

  78. Ruster, B., Gottig, S., Ludwig, R.J., et al. (2006) Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood. 108, 3938–3944.

    Article  PubMed  CAS  Google Scholar 

  79. Ley, K., Laudanna, C., Cybulsky, M.I., et al. (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat. Rev. Immunol. 7, 678–689.

    Article  PubMed  CAS  Google Scholar 

  80. Goetz, D.J., el-Sabban, M.E., Pauli, B.U., et al. (1994) Dynamics of neutrophil rolling over stimulated endothelium in vitro. Biophys. J. 66, 2202–2209.

    Article  PubMed  CAS  Google Scholar 

  81. Sackstein, R., Merzaban, J.S., Cain, D.W., et al. (2008) Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat. Med. 14, 181–187.

    Article  PubMed  CAS  Google Scholar 

  82. Toma, C., Wagner, W.R., Bowry, S., et al. (2009) Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo observations of cell kinetics. Circ. Res. 104, 398–402.

    Article  PubMed  CAS  Google Scholar 

  83. Brooke, G., Cook, M., Blair, C., et al. (2007) Therapeutic applications of mesenchymal stromal cells. Semin. Cell. Dev. Biol. 18, 846–858.

    Article  PubMed  CAS  Google Scholar 

  84. Tögel, F. and Westenfelder, C. (2007) Adult bone marrow-derived stem cells for organ regeneration and repair. Dev. Dynam. 236, 3321–3331.

    Article  CAS  Google Scholar 

  85. Giordano, A., Galderisi, U. and Marino, I.R. (2007) From the laboratory bench to the patient’s bedside: An update on clinical trials with mesenchymal stem cells. J. Cell. Physiol. 211, 27–35.

    Article  PubMed  CAS  Google Scholar 

  86. Lin, F. (2008) Renal repair: role of bone marrow stem cells. Pediatr. Nephrol. 23, 851–861.

    Article  PubMed  Google Scholar 

  87. Hou, L. and Hong, T. (2008) Stem cells and neurodegenerative diseases. Sci. China C. Life. Sci. 51, 287–294.

    Article  PubMed  Google Scholar 

  88. Uccelli, A., Moretta, L. and Pistoia, V. (2008) Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 8, 726–736.

    Article  PubMed  CAS  Google Scholar 

  89. Lee, K.D. (2007) Applications of mesenchymal stem cells: an updated review. Chang Gung Med. J. 31, 228–236.

    CAS  Google Scholar 

  90. Dharmasaroja, P. (2009) Bone marrow-derived mesenchymal stem cells for the treatment of ischemic stroke. J. Clin. Neurosci. 16, 12–20.

    Article  PubMed  Google Scholar 

  91. Loebinger, M.R., Sage, E.K. and Janes, S.M. (2008) Mesenchymal Stem Cells as Vectors for Lung Disease. Proc. Am. Thorac. Soc. 5, 711–716.

    Article  PubMed  Google Scholar 

  92. Summer, R. and Fine, A. (2008) Mesenchymal Progenitor Cell Research: Limitations and Recommendations. Proc. Am. Thorac. Soc. 5, 707–710.

    Article  PubMed  Google Scholar 

  93. Bongso, A., Fong, C.Y. and Gauthaman, K. (2008) Taking stem cells to the clinic: Major challenges. J. Cell. Biochem. 105, 1352–1360.

    Article  PubMed  CAS  Google Scholar 

  94. Shi, R.Z. and Li, Q.P. (2008) Improving outcome of transplanted mesenchymal stem cells for ischemic heart disease. Biochem. Biophys. Res. Comm. 376, 247–250.

    Article  PubMed  CAS  Google Scholar 

  95. Karnoub, A.E., Dash, A.B., Vo, A.P. et al. (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 449, 557–563.

    Article  PubMed  CAS  Google Scholar 

  96. Rubio, D., Garcia-Castro, J., Martin, M.C. et al. (2005) Spontaneous Human Adult Stem Cell Transformation. Cancer Res. 65, 3035–3039.

    PubMed  CAS  Google Scholar 

  97. Cheng, Z., Ou, L., Zhou, X., et al. (2008) Targeted Migration of Mesenchymal Stem Cells Modified With CXCR4 Gene to Infarcted Myocardium Improves Cardiac Performance. Mol. Ther. 16, 571–579.

    Article  PubMed  CAS  Google Scholar 

  98. Kumar, S. and Ponnazhagan, S. (2007) Bone homing of mesenchymal stem cells by ectopic {alpha}4 integrin expression. FASEB J. 21, 3917–3927.

    Article  PubMed  CAS  Google Scholar 

  99. Lee, R.J., Fang, Q., Davol, P.A., et al. (2007) Antibody Targeting of Stem Cells to Infarcted Myocardium. Stem Cells. 25, 712–717.

    Article  PubMed  CAS  Google Scholar 

  100. Dennis, J.E., Cohen, N., Goldberg, V.M., et al. (2004) Targeted delivery of progenitor cells for cartilage repair. J. Orthop. Res. 22, 735–741.

    Article  PubMed  CAS  Google Scholar 

  101. Sarkar, D., Vemula, P.K., Teo, G.S.L., et al. (2008) Chemical Engineering of Mesenchymal Stem Cells to Induce a Cell Rolling Response. Bioconjugate Chem. 19, 2105–2109.

    Article  CAS  Google Scholar 

  102. Muschler, G.F., Nakamoto, C. and Griffith, L.G. (2004) Engineering principles of clinical cell-based tissue engineering. J. Bone Joint Surg. Am. 86A, 1541–1558.

    Google Scholar 

  103. Walczak, P., Zhang, J., Gilad, A.A., et al. (2008) Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke. 39, 1569–1574.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jeffrey M. Karp .

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Zhao, W. et al. (2011). Therapeutic Applications of Mesenchymal Stem/Multipotent Stromal Cells. In: Appasani, K., Appasani, R. (eds) Stem Cells & Regenerative Medicine. Stem Cell Biology and Regenerative Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-860-7_12

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