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Wharton’s Jelly Stem Cells

  • Marina Bastawrous
  • Mibel M. Pabón
  • Sandra Acosta
  • Ike de la Peña
  • Diana Hernandez-Ontiveros
  • Meaghan Staples
  • Kazutaka Shinozuka
  • Paolina Pantcheva
  • Naoki Tajiri
  • Yuji Kaneko
  • Cesar V. Borlongan
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Mesenchymal stromal cells (MSCs) have been always considered as a useful option for therapeutic purposes. MSCs can be derived from many sources, perhaps one of the most therapeutically valuable sources is the Wharton’s Jelly (WJ), a gelatinous tissue layer found within the umbilical cord that contains myofibroblast-like stromal cells. Previous studies investigating Wharton’s Jelly-derived MSCs reveal that they have more powerful proliferative, immunosuppressive and therapeutic activities compared to MSCs derived from adult bone marrow or adipose tissue. The present review discusses the phenotypic features, potential therapeutic uses and optimization of experimental protocols for WJ-derived stem cells. Previous work show successful results when WJ-MSCs were used as transplantable cells for treatment of various diseases (e.g., cancer, chronic liver disease, cardiovascular diseases, nerve, cartilage, tendon injury and degenerated intervertebral disc). These positive results are attributed to favorable transplantable features the WJ-MSCs display which include ease of sourcing, in vitro expandability, differentiation abilities, immune-evasion and immune-regulation capacities. However, further research work is demanded to harness the benefits of WJ-MSCs into clinical application.

Keywords

Adult stem cells Placenta Mesenchymal cells Biology Transplantation Diseases 

Notes

Acknowledgments

This work was supported by NIH NINDS RO1 1R01NS071956-01 (C.V.B.), James and Esther King Biomedical Research Program 09KB-01-23123 (C.V.B.) and 1KG01-33966 (C.V.B.).

References

  1. 1.
    La Rocca G. Connecting the dots: the promises of Wharton’s Jelly stem cells for tissue repair and regeneration. Open Tissue Eng Regen Med J. 2011;4:3–5.CrossRefGoogle Scholar
  2. 2.
    McElreavey KD, Irvine AI, Ennis KT, McLean WH. Isolation, culture and characterisation of fibroblast-like cells derived from the Wharton’s Jelly portion of human umbilical cord. Biochem Soc Trans. 1991;19:29S.CrossRefPubMedGoogle Scholar
  3. 3.
    Wharton T. Adenographia. Oxford: Oxford University Press; 1996. Transl. Freer S.Google Scholar
  4. 4.
    Chacko AW, Reynolds SRM. Architecture of distended and nondistended human umbilical cord tissues, with special reference to the arteries and veins. Contrib Embryol. 1954;35:135–50.Google Scholar
  5. 5.
    Kadner A, Hoerstrup SP, Tracy J, Breymann C, Maurus CF, Melnitchouk S, Kadner G, Zund G, Turina M. Human umbilical cord cells: a new cell source for cardiovascular tissue engineering. Ann Thorac Surg. 2002;74:S1422–1428.CrossRefPubMedGoogle Scholar
  6. 6.
    Kadner A, Zund G, Maurus C, Breymann C, Yakarisik S, Kadner G, Turina M, Hoerstrup SP. Human umbilical cord cells for cardiovascular tissue engineering: a comparative study. Eur J Cardiothorac Surg. 2004;25:635–41.CrossRefPubMedGoogle Scholar
  7. 7.
    Mitchell KE, Weiss ML, Mitchell BM, Martin P, Davis D, Morales L, Helwig B, Beerenstrauch M, Abou-Easa K, Hildreth T, et al. Matrix cells from Wharton’s Jelly form neurons and glia. Stem Cells. 2003;21:50–60.CrossRefPubMedGoogle Scholar
  8. 8.
    Naughton BA, San Roman J, Liu K, Purchio A, Pavelec R, Rekettye L. Cells isolated from Wharton’s Jelly of the human umbilical cord develop a cartilage phenotype when treated with tgf-β in vitro. FASEB J. 1997;11:A19.Google Scholar
  9. 9.
    Purchio AF, Naughton BA, Roman, JS. Production of cartilage tissue using cells isolated from Wharton’s Jelly. U.S. Patent 5,919,702. 1999.Google Scholar
  10. 10.
    Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate msc-like cells from umbilical cord. Stem Cells. 2003;21:105–10.CrossRefPubMedGoogle Scholar
  11. 11.
    Takechi K, Kuwabara Y, Mizuno M. Ultrastructural and immunohistochemical studies of Wharton's Jelly umbilical cord cells. Placenta. 1993;14:235–45.CrossRefPubMedGoogle Scholar
  12. 12.
    Kobayashi K, Kubota T, Aso T. Study on myofibroblast differentiation in the stromal cells of Wharton’s Jelly: expression and localization of alpha-smooth muscle actin. Early Hum Dev. 1998;51:223–33.CrossRefPubMedGoogle Scholar
  13. 13.
    Markov V, Kusumi K, Tadesse MG, William DA, Hall DM, Lounev V, Carlton A, Leonard J, Cohen RI, Rappaport EF, et al. Identification of cord blood-derived mesenchymal stem/stromal cell populations with distinct growth kinetics, differentiation potentials, and gene expression profiles. Stem Cells Dev. 2007;16:53–73.CrossRefPubMedGoogle Scholar
  14. 14.
    Baudin B, Bruneel A, Bosselut N, Vaubourdolle M. A protocol for isolation and culture of human umbilical vein endothelial cells. Nat Protoc. 2007;2:481–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Wang XY, Lan Y, He WY, Zhang L, Yao HY, Hou CM, Tong Y, Liu YL, Yang G, Liu XD, et al. Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos. Blood. 2008;111:2436–43.CrossRefPubMedGoogle Scholar
  16. 16.
    Bongso A, Fong CY. The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton’s Jelly of the human umbilical cord. Stem Cell Rev. 2013;9:226–40.CrossRefPubMedGoogle Scholar
  17. 17.
    Jeschke MG, Gauglitz GG, Phan TT, Herndon DN, Kita K. Umbilical cord lining membrane and Wharton’s Jelly-derived mesenchymal stem cells: the similarities and differences. Open Tissue Eng Regen Med J. 2011;4:21–7.CrossRefGoogle Scholar
  18. 18.
    Prasanna SJ, Jahnavi VS. Wharton’s jelly mesenchymal stem cells as off-the -shelf cellular therapeutics: a closer look into their regenerative and immunomodulatory properties. Open Tissue Eng Regen Med J. 2011;4:28–38.CrossRefGoogle Scholar
  19. 19.
    Troyer DL, Weiss ML. Wharton's jelly-derived cells are a primitive stromal cell population. Stem Cells. 2008;26:591–9.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DO, Tukun A, Uckan D, Can A. Biology of stem cells in human umbilical cord stroma: In situ and in vitro surveys. Stem Cells. 2007;25:319–31.CrossRefPubMedGoogle Scholar
  21. 21.
    Nanaev AK, Kohnen G, Milovanov AP, Domogatsky SP, Kaufmann P. Stromal differentiation and architecture of the human umbilical cord. Placenta. 1997;18:53–64.CrossRefPubMedGoogle Scholar
  22. 22.
    Can A, Karahuseyinoglu S. Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells. 2007;25:2886–95.CrossRefPubMedGoogle Scholar
  23. 23.
    Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 2007;25:1384–92.CrossRefPubMedGoogle Scholar
  24. 24.
    Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE. Human umbilical cord perivascular (hucpv) cells: a source of mesenchymal progenitors. Stem Cells. 2005;23:220–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Kita K, Gauglitz GG, Phan TT, Herndon DN, Jeschke MG. Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining membrane. Stem Cells Dev. 2010;19:491–502.CrossRefPubMedGoogle Scholar
  26. 26.
    Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB. Pro-inflammatory cytokines, ifngamma and tnfalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS One. 2010;5, e9016.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    La Rocca G, Anzalone R, Corrao S, Magno F, Loria T, Lo Iacono M, Di Stefano A, Giannuzzi P, Marasa L, Cappello F, et al. Isolation and characterization of oct-4+/hla-g+ mesenchymal stem cells from human umbilical cord matrix: Differentiation potential and detection of new markers. Histochem Cell Biol. 2009;131:267–82.CrossRefPubMedGoogle Scholar
  28. 28.
    Rachakatla RS, Pyle MM, Ayuzawa R, Edwards SM, Marini FC, Weiss ML, Tamura M, Troyer D. Combination treatment of human umbilical cord matrix stem cell-based interferon-beta gene therapy and 5-fluorouracil significantly reduces growth of metastatic human breast cancer in scid mouse lungs. Cancer Invest. 2008;26:662–70.CrossRefPubMedGoogle Scholar
  29. 29.
    Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, Troyer D, McIntosh KR. Immune properties of human umbilical cord Wharton’s jelly-derived cells. Stem Cells. 2008;26:2865–74.CrossRefPubMedGoogle Scholar
  30. 30.
    Deuse T, Stubbendorff M, Tang-Quan K, Phillips N, Kay MA, Eiermann T, Phan TT, Volk HD, Reichenspurner H, Robbins RC, et al. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplant. 2011;20:655–67.CrossRefPubMedGoogle Scholar
  31. 31.
    Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, Borg C, Saas P, Tiberghien P, Rouas-Freiss N, et al. Human leukocyte antigen-g5 secretion by human mesenchymal stem cells is required to suppress t lymphocyte and natural killer function and to induce cd4+cd25highfoxp3+ regulatory t cells. Stem Cells. 2008;26:212–22.CrossRefPubMedGoogle Scholar
  32. 32.
    Griffin MD, Ritter T, Mahon BP. Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther. 2010;21:1641–55.CrossRefPubMedGoogle Scholar
  33. 33.
    Zarkhin V, Talisetti A, Li L, Wozniak LJ, McDiarmid SV, Cox K, Esquivel C, Sarwal MM. Expression of soluble hla-g identifies favorable outcomes in liver transplant recipients. Transplantation. 2010;90:1000–5.CrossRefPubMedGoogle Scholar
  34. 34.
    Djouad F, Charbonnier LM, Bouffi C, Louis-Plence P, Bony C, Apparailly F, Cantos C, Jorgensen C, Noel D. Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells. 2007;2025–2032:25.Google Scholar
  35. 35.
    Cho PS, Messina DJ, Hirsh EL, Chi N, Goldman SN, Lo DP, Harris IR, Popma SH, Sachs DH, Huang CA. Immunogenicity of umbilical cord tissue derived cells. Blood. 2008;111:430–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress t-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838–43.CrossRefPubMedGoogle Scholar
  37. 37.
    Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815–22.CrossRefPubMedGoogle Scholar
  38. 38.
    Najar M, Rouas R, Raicevic G, Boufker HI, Lewalle P, Meuleman N, Bron D, Toungouz M, Martiat P, Lagneaux L. Mesenchymal stromal cells promote or suppress the proliferation of t lymphocytes from cord blood and peripheral blood: the importance of low cell ratio and role of interleukin-6. Cytotherapy. 2009;11:570–83.CrossRefPubMedGoogle Scholar
  39. 39.
    Gotherstrom C, Ringden O, Westgren M, Tammik C, Le Blanc K. Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells. Bone Marrow Transplant. 2003;32:265–72.CrossRefPubMedGoogle Scholar
  40. 40.
    Tipnis S, Viswanathan C, Majumdar AS. Immunosuppressive properties of human umbilical cord-derived mesenchymal stem cells: role of b7-h1 and ido. Immunol Cell Biol. 2010;88:795–806.CrossRefPubMedGoogle Scholar
  41. 41.
    Conconi MT, Di Liddo R, Tommasini M, Calore C, Parnigotto PP. Phenotype and differentiation potential of stromal populations obtained from various zones of human umbilical cord: an overview. Open Tissue Eng Regen Med J. 2011;4:6–20.CrossRefGoogle Scholar
  42. 42.
    Rey Nores JE, Bensussan A, Vita N, Stelter F, Arias MA, Jones M, Lefort S, Borysiewicz LK, Ferrara P, Labeta MO. Soluble cd14 acts as a negative regulator of human t cell activation and function. Eur J Immunol. 1999;29:265–76.CrossRefPubMedGoogle Scholar
  43. 43.
    Conconi MT, Burra P, Di Liddo R, Calore C, Turetta M, Bellini S, Bo P, Nussdorfer GG, Parnigotto PP. Cd105(+) cells from Wharton’s jelly show in vitro and in vivo myogenic differentiative potential. Int J Mol Med. 2006;18:1089–96.PubMedGoogle Scholar
  44. 44.
    Dabelea D, Pettitt DJ. Intrauterine diabetic environment confers risks for type 2 diabetes mellitus and obesity in the offspring, in addition to genetic susceptibility. J Pediatr Endocrinol Metab. 2001;14:1085–91.PubMedGoogle Scholar
  45. 45.
    Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003;111:e221–226.CrossRefPubMedGoogle Scholar
  46. 46.
    Clausen TD, Mathiesen ER, Hansen T, Pedersen O, Jensen DM, Lauenborg J, Damm P. High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia. Diabetes Care. 2008;31:340–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Wang H, Qiu X, Ni P, Qiu X, Lin X, Wu W, Xie L, Lin L, Min J, Lai X, Chen Y, Ho G, Ma L. Immunological characteristics of human umbilical cord mesenchymal stem cells and the therapeutic effects of their transplantion on hyperglycemia in diabetic rats. Int J Mol Med. 2014;33(2):263–70.PubMedPubMedCentralGoogle Scholar
  48. 48.
    He H, Nagamura-Inoue T, Tsunoda H, Yuzawa M, Yamamoto Y, Yorozu P, Agata H, Tojo A. Stage-specific embryonic antigen 4 in Wharton’s Jelly-derived mesenchymal stem cells is not a marker for proliferation and multipotency. Tissue Eng Part A. 2013;20:1314–24.CrossRefGoogle Scholar
  49. 49.
    Sharma T, Kumari P, Pincha N, Mutukula N, Saha S, Jana SS, Ta M. Inhibition of non-muscle myosin II leads to G0/G1 arrest of Wharton’s jelly-derived mesenchymal stromal cells. Cytotherapy. 2014;16:640–52.CrossRefPubMedGoogle Scholar
  50. 50.
    Gatta V, D’Aurora M, Lanuti P, Pierdomenico L, Sperduti S, Palka G, Gesi M, Marchisio M, Miscia S, Stuppia L. Gene expression modifications in Wharton’s Jelly mesenchymal stem cells promoted by prolonged in vitro culturing. BMC Genomics. 2013;14:635.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM. White fat progenitor cells reside in the adipose vasculature. Science. 2008;322:583–6.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Tchoukalova Y, Koutsari C, Jensen M. Committed subcutaneous preadipocytes are reduced in human obesity. Diabetologia. 2007;50:151–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Pierdomenico L, Lanuti P, Lachmann R, Grifone G, Cianci E, Gialò L, Pacella S, Romano M, Vitacolonna E, Miscia S. Diabetes mellitus during pregnancy interferes with the biological characteristics of Wharton’s jelly mesenchymal stem cells. Open Tissue Eng Regen Med J. 2011;4:103–11.CrossRefGoogle Scholar
  54. 54.
    Ayuzawa R, Doi C, Rachakatla RS, Pyle MM, Maurya DK, Troyer D, Tamura M. Naive human umbilical cord matrix derived stem cells significantly attenuate growth of human breast cancer cells in vitro and in vivo. Cancer Lett. 2009;280:31–7.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Ganta C, Chiyo D, Ayuzawa R, Rachakatla R, Pyle M, Andrews G, Weiss M, Tamura M, Troyer D. Rat umbilical cord stem cells completely abolish rat mammary carcinomas with no evidence of metastasis or recurrence 100 days post-tumor cell inoculation. Cancer Res. 2009;69:1815–20.CrossRefPubMedGoogle Scholar
  56. 56.
    Tamura M, Kawabata A, Ohta N, Uppalapati L, Becker KG, Troyer D. Wharton’s jelly stem cells as agents for cancer therapy. Open Tissue Eng Regen Med J. 2011;4:39–47.CrossRefGoogle Scholar
  57. 57.
    Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, et al. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res. 2005;65:3307–18.PubMedGoogle Scholar
  58. 58.
    Rachakatla RS, Marini F, Weiss ML, Tamura M, Troyer D. Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors. Cancer Gene Ther. 2007;14:828–35.CrossRefPubMedGoogle Scholar
  59. 59.
    Matsuzuka T, Rachakatla RS, Doi C, Maurya DK, Ohta N, Kawabata A, Pyle MM, Pickel L, Reischman J, Marini F, et al. Human umbilical cord matrix-derived stem cells expressing interferon-beta gene significantly attenuate bronchioloalveolar carcinoma xenografts in scid mice. Lung Cancer. 2010;70:28–36.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Scheers I, Lombard C, Najimi M, Sokal E. Cell therapy for the treatment of metabolic liver disease: an update on the umbilical cord derived stem cells candidates. Open Tissue Eng Regen Med J. 2011;4:48–53.CrossRefGoogle Scholar
  61. 61.
    Campard D, Lysy PA, Najimi M, Sokal EM. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology. 2008;134:833–48.CrossRefPubMedGoogle Scholar
  62. 62.
    Anzalone R, Lo Iacono M, Corrao S, Magno F, Loria T, Cappello F, Zummo G, Farina F, La Rocca G. New emerging potentials for human Wharton’s jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity. Stem Cells Dev. 2010;19:423–38.CrossRefPubMedGoogle Scholar
  63. 63.
    Semenov O, Breymann C. Mesenchymal stem cells derived from Wharton’s jelly and their potential for cardio-vascular tissue engineering. Open Tissue Eng Regen Med J. 2011;4:64–71.CrossRefGoogle Scholar
  64. 64.
    Mayer Jr JE. Uses of homograft conduits for right ventricle to pulmonary artery connections in the neonatal period. Semin Thorac Cardiovasc Surg. 1995;7:130–2.PubMedGoogle Scholar
  65. 65.
    Schoen FJ, Levy RJ. Tissue heart valves: current challenges and future research perspectives. J Biomed Mater Res. 1999;47:439–65.CrossRefPubMedGoogle Scholar
  66. 66.
    Shinoka T, Ma PX, Shum-Tim D, Breuer CK, Cusick RA, Zund G, Langer R, Vacanti JP, Mayer Jr JE. Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. Circulation. 1996;94:II164–168.PubMedGoogle Scholar
  67. 67.
    Kenar H, Kose GT, Toner M, Kaplan DL, Hasirci V. A 3d aligned microfibrous myocardial tissue construct cultured under transient perfusion. Biomaterials. 2011;32:5320–9.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Lo Iacono M, Anzalone R, Corrao S, Giuffrè M, Di Stefano A, Giannuzzi P, Cappello F, Farina F, La Rocca G. Perinatal and Wharton’s jelly-derived mesenchymal stem cells in cartilage regenerative medicine and tissue engineering strategies. Open Tissue Eng Regen Med J. 2011;4:72–81.CrossRefGoogle Scholar
  69. 69.
    Arufe MC, De la Fuente A, Mateos J, Fuentes I, De Toro FJ, Blanco FJ. Analysis of the chondrogenic potential and secretome of mesenchymal stem cells derived from human umbilical cord stroma. Stem Cells Dev. 2011;20:1199–212.CrossRefPubMedGoogle Scholar
  70. 70.
    Fong CY, Subramanian A, Gauthaman K, Venugopal J, Biswas A, Ramakrishna S, Bongso A. Human umbilical cord Wharton’s jelly stem cells undergo enhanced chondrogenic differentiation when grown on nanofibrous scaffolds and in a sequential two-stage culture medium environment. Stem Cell Rev. 2012;8:195–209.CrossRefPubMedGoogle Scholar
  71. 71.
    Wang L, Seshareddy K, Weiss ML, Detamore MS. Effect of initial seeding density on human umbilical cord mesenchymal stromal cells for fibrocartilage tissue engineering. Tissue Eng Part A. 2009;15:1009–17.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Wang L, Zhao L, Detamore MS. Human umbilical cord mesenchymal stromal cells in a sandwich approach for osteochondral tissue engineering. J Tissue Eng Regen Med. 2011;5:712–21.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Chon BH, Lee EJ, Jing L, Setton LA, Chen J. Human umbilical cord mesenchymal stromal cells exhibit immature nucleus pulposus cell phenotype in a laminin-rich pseudo-three-dimensional culture system. Stem Cell Res Ther. 2013;4(5):120.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Hall S. Nerve repair: a neurobiologist’s view. J Hand Surg. 2001;26:129–36.CrossRefGoogle Scholar
  75. 75.
    Ishikawa N, Suzuki Y, Ohta M, Cho H, Suzuki S, Dezawa M, Ide C. Peripheral nerve regeneration through the space formed by a chitosan gel sponge. J Biomed Mater Res A. 2007;83:33–40.CrossRefPubMedGoogle Scholar
  76. 76.
    Ohta M, Suzuki Y, Chou H, Ishikawa N, Suzuki S, Tanihara M, Suzuki Y, Mizushima Y, Dezawa M, Ide C. Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve. J Biomed Mater Res A. 2004;71:661–8.CrossRefPubMedGoogle Scholar
  77. 77.
    Dezawa M, Takahashi I, Esaki M, Takano M, Sawada H. Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur J Neurosci. 2001;14:1771–6.CrossRefPubMedGoogle Scholar
  78. 78.
    Matsuse D, Kitada M, Kohama M, Nishikawa K, Makinoshima H, Wakao S, Fujiyoshi Y, Heike T, Nakahata T, Akutsu H, et al. Human umbilical cord-derived mesenchymal stromal cells differentiate into functional schwann cells that sustain peripheral nerve regeneration. J Neuropathol Exp Neurol. 2010;69:973–85.CrossRefPubMedGoogle Scholar
  79. 79.
    Kuroda Y, Kitada M, Wakao S, Dezawa M. Mesenchymal stem cells and umbilical cord as sources for schwann cell differentiation: their potential in peripheral nerve repair. Open Tissue Eng Regen Med J. 2011;4:54–63.CrossRefGoogle Scholar
  80. 80.
    Peng J, Wang Y, Zhang L, Zhao B, Zhao Z, Chen J, Guo Q, Liu S, Sui X, Xu W, et al. Human umbilical cord Wharton’s jelly-derived mesenchymal stem cells differentiate into a schwann-cell phenotype and promote neurite outgrowth in vitro. Brain Res Bull. 2011;84:235–43.CrossRefPubMedGoogle Scholar
  81. 81.
    Xu Q, Zhang HT, Liu K, Rao JH, Liu XM, Wu L, Xu BN. In vitro and in vivo magnetic resonance tracking of sinerem-labeled human umbilical mesenchymal stromal cell-derived schwann cells. Cell Mol Neurobiol. 2011;31:365–75.CrossRefPubMedGoogle Scholar
  82. 82.
    Zhang X, Zhang Q, Li W, Nie D, Chen W, Xu C, Yi X, Shi J, Tian M, Qin J, Jin G, Tu W. Therapeutic effect of human umbilical cord mesenchymal stem cells on neonatal rat hypoxic-ischemic encephalopathy. J Neurosci Res. 2014;92(1):35–45.CrossRefPubMedGoogle Scholar
  83. 83.
    Hsieh JY, Wang HW, Chang SJ, Liao KH, Lee IH, Lin WS, Wu CH, Lin WY, Cheng SM. Mesenchymal stem cells from human umbilical cord express preferentially secreted ‑factors related to neuroprotection, neurogenesis, and angiogenesis. PLoS One. 2013;8(8), e72604.Google Scholar
  84. 84.
    Paldino E, Cenciarelli C, Giampaolo A, Milazzo L, Pescatori M, Hassan HJ, Casalbore P. Induction of dopaminergic neurons from human Wharton’s jelly mesenchymal stem cell by forskolin. J Cell Physiol. 2014;229(2):232–44.CrossRefPubMedGoogle Scholar
  85. 85.
    López Y, Seshareddy K, Trevino E, Cox J, Weiss ML. Evaluating the impact of oxygen concentration and plating density on human Wharton’s jelly-derived mesenchymal stromal cells. Open Tissue Eng Regen Med J. 2011;4:82–94.CrossRefGoogle Scholar
  86. 86.
    Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, Fries JW, Tiemann K, Bohlen H, Hescheler J, et al. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood. 2007;110:1362–9.CrossRefPubMedGoogle Scholar
  87. 87.
    Bittira B, Kuang JQ, Al-Khaldi A, Shum-Tim D, Chiu RC. In vitro preprogramming of marrow stromal cells for myocardial regeneration. Ann Thorac Surg. 2002;74:1154–9. discussion 1159–1160.CrossRefPubMedGoogle Scholar
  88. 88.
    Tomita S, Mickle DA, Weisel RD, Jia ZQ, Tumiati LC, Allidina Y, Liu P, Li RK. Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg. 2002;123:1132–40.CrossRefPubMedGoogle Scholar
  89. 89.
    Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells. 2004;22:1330–7.CrossRefPubMedGoogle Scholar
  90. 90.
    Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, et al. Adult cardiac sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem. 2004;279:11384–91.CrossRefPubMedGoogle Scholar
  91. 91.
    Maltsev VA, Rohwedel J, Hescheler J, Wobus AM. Embryonic stem cells differentiate in vitro into cardiomyocytes representing sinusnodal, atrial and ventricular cell types. Mech Dev. 1993;44:41–50.CrossRefPubMedGoogle Scholar
  92. 92.
    Hollweck T, Hartmann I, Eblenkamp M, Wintermantel E, Reichart B, Überfuhr P, Eissner G. Cardiac differentiation of human wharton's jelly stem cells—experimental comparison of protocols. Open Tissue Eng Regen Med J. 2011;4:95–102.CrossRefGoogle Scholar
  93. 93.
    Fathi F, Murasawa S, Hasegawa S, Asahara T, Kermani AJ, Mowla SJ. Cardiac differentiation of p19cl6 cells by oxytocin. Int J Cardiol. 2009;134:75–81.CrossRefPubMedGoogle Scholar
  94. 94.
    Lopez Y, Lutjemeier B, Seshareddy K, Trevino EM, Hageman KS, Musch TI, Borgarelli M, Weiss ML. Wharton’s jelly or bone marrow mesenchymal stromal cells improve cardiac function following myocardial infarction for more than 32 weeks in a rat model: a preliminary report. Curr Stem Cell Res Ther. 2013;8:46–59.CrossRefPubMedGoogle Scholar
  95. 95.
    Schugar RC, Chirieleison SM, Wescoe KE, Schmidt BT, Askew Y, Nance JJ, Evron JM, Peault B, Deasy BM. High harvest yield, high expansion, and phenotype stability of cd146 mesenchymal stromal cells from whole primitive human umbilical cord tissue. J Biomed Biotechnol. 2009;2009:789526.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Farias VA, Linares-Fernandez JL, Penalver JL, Paya Colmenero JA, Ferron GO, Duran EL, Fernandez RM, Olivares EG, O'Valle F, Puertas A, et al. Human umbilical cord stromal stem cell express cd10 and exert contractile properties. Placenta. 2011;32:86–95.CrossRefPubMedGoogle Scholar
  97. 97.
    Sarugaser R, Hanoun L, Keating A, Stanford WL, Davies JE. Human mesenchymal stem cells self-renew and differentiate according to a deterministic hierarchy. PLoS One. 2009;4, e6498.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Sarugaser R, Ennis J, Stanford WL, Davies JE. Isolation, propagation, and characterization of human umbilical cord perivascular cells (hucpvcs). Methods Mol Biol. 2009;482:269–79.CrossRefPubMedGoogle Scholar
  99. 99.
    Lange-Consiglio A, Corradetti B, Rutigliano L, Cremonesi F, Bizzarro D. In vitro studies of horse umbilical cord matrix-derived cells: from characterization to labeling for magnetic resonance imaging. Open Tissue Eng Regen Med J. 2011;4:120–33.CrossRefGoogle Scholar
  100. 100.
    Li XX, Li KA, Qin JB, Ye KC, Yang XR, Li WM, Xie QS, Jiang ME, Zhang GX, Lu XW. In vivo MRI tracking of iron oxide nanoparticle-labeled human mesenchymal stem cells in limb ischemia. Int J Nanomedicine. 2013;8:1063–73.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Marina Bastawrous
    • 1
  • Mibel M. Pabón
    • 1
  • Sandra Acosta
    • 1
  • Ike de la Peña
    • 2
  • Diana Hernandez-Ontiveros
    • 3
  • Meaghan Staples
    • 1
  • Kazutaka Shinozuka
    • 1
  • Paolina Pantcheva
    • 1
  • Naoki Tajiri
    • 1
  • Yuji Kaneko
    • 1
  • Cesar V. Borlongan
    • 1
  1. 1.Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of MedicineUniversity of South Florida College of MedicineTampaUSA
  2. 2.Pharmaceutical and Administrative SciencesLoma Linda UniversityLoma LindaUSA
  3. 3.Department of Physiology and PharmacologyUniversity of South Florida College of MedicineTampaUSA

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