Skip to main content
SpringerLink
Log in

Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges

  • Review
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Ischemic stroke is a focal cerebral insult that often leads to many adverse neurological complications severely affecting the quality of life. The prevalence of stroke is increasing throughout the world, while the efficacy of current pharmacological therapies remains unclear. As a neuroregenerative therapy, the implantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) has shown great possibility to restore function after stroke. This review article provides an update role of hUC-MSCs implantation in the treatment of ischemic stroke. With the unique “immunosuppressive and immunoprivilege” property, hUC-MSCs are advised to be an important candidate for allogeneic cell treatment. Nevertheless, most of the treatments are still at primary stage and not clinically feasible at the current time. Several uncertain problems, such as culture conditions, allograft rejection, and potential tumorigenicity, are the choke points in this cellular therapy. More preclinical researches and clinical studies are needed before hUC-MSCs implantation can be used as a routinely applied clinical therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zhang L, Li Y, Zhang C, Chopp M, Gosiewska A, Hong K. Delayed administration of human umbilical tissue-derived cells improved neurological functional recovery in a rodent model of focal ischemia. Stroke 2011; 42(5): 1437–1444

    PubMed  Google Scholar 

  2. McGuckin CP, Jurga M, Miller AM, Sarnowska A, Wiedner M, Boyle NT, Lynch MA, Jablonska A, Drela K, Lukomska B, Domanska-Janik K, Kenner L, Moriggl R, Degoul O, Perruisseau-Carrier C, Forraz N. Ischemic brain injury: a consortium analysis of key factors involved in mesenchymal stem cell-mediated inflammatory reduction. Arch Biochem Biophys 2013; 534(1–2): 88–97

    CAS  PubMed  Google Scholar 

  3. Blum B, Benvenisty N. The tumorigenicity of human embryonic stem cells. Adv Cancer Res 2008; 100: 133–158

    PubMed  Google Scholar 

  4. Cai J, Li W, Su H, Qin D, Yang J, Zhu F, Xu J, He W, Guo X, Labuda K, Peterbauer A, Wolbank S, Zhong M, Li Z, Wu W, So KF, Redl H, Zeng L, Esteban MA, Pei D. Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells. J Biol Chem 2010; 285(15): 11227–11234

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663–676

    CAS  PubMed  Google Scholar 

  6. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143–147

    CAS  PubMed  Google Scholar 

  7. Li C, Li B, Dong Z, Gao L, He X, Liao L, Hu C, Wang Q, Jin Y. Lipopolysaccharide differentially affects the osteogenic differentiation of periodontal ligament stem cells and bone marrow mesenchymal stem cells through Toll-like receptor 4 mediated nuclear factor κB pathway. Stem Cell Res Ther 2014; 5(3): 67

    PubMed Central  PubMed  Google Scholar 

  8. Li D, Wang C, Shan W. Human amnion tissue injected with human umbilical cord mesenchymal stem cells repairs damaged sciatic nerves in rats. Neural Regen Res 2012; 7(23): 1771–1778

    PubMed Central  PubMed  Google Scholar 

  9. 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(2): 220–229

    PubMed  Google Scholar 

  10. Guo J, Fan HH, Qian YX. IFN-γ can promote the immunosuppressive capacity of human umbilical cord mesenchymal stem cells by expression of indoleamine 2,3-dioxygenase. J Diagn Concepts Pract 2010; 9(3): 181–185

    Google Scholar 

  11. Li DR, Cai JH. Methods of isolation, expansion, differentiating induction and preservation of human umbilical cord mesenchymal stem cells. Chin Med J (Engl) 2012; 125(24): 4504–4510

    CAS  Google Scholar 

  12. Kadam SS, Tiwari S, Bhonde RR. Simultaneous isolation of vascular endothelial cells and mesenchymal stem cells from the human umbilical cord. In Vitro Cell Dev Biol Anim 2009; 45(1–2): 23–27

    PubMed  Google Scholar 

  13. Dong M, Chen J, Ma YQ. Efficient method for isolation of human umbilical cord mesenchymal stem cells. Chin J Tissue Eng Res (Zhongguo Zu Zhi Gong Cheng Yan Jiu) 2012; 16(45): 8406–8412 (in Chinese)

    CAS  Google Scholar 

  14. Liu SP, Ding DC, Wang HJ, Su CY, Lin SZ, Li H, Shyu WC. Nonsenescent Hsp27-upregulated MSCs implantation promotes neuroplasticity in stroke model. Cell Transplant 2010; 19(10): 1261–1279

    PubMed  Google Scholar 

  15. Sensebé L, Krampera M, Schrezenmeier H, Bourin P, Giordano R. Mesenchymal stem cells for clinical application. Vox Sang 2010; 98(2): 93–107

    PubMed  Google Scholar 

  16. Li JJ, Li D, Ju XL, Liu WB. Umbilical cord-derived mesenchymal stem cells retain immunomodulatory and anti-oxidative activities after neural induction. Neural Regen Res 2012; 7(34): 2663–2672

    PubMed Central  CAS  PubMed  Google Scholar 

  17. Arufe MC, De la Fuente A, Fuentes I, Toro FJ, Blanco FJ.Umbilical cord as a mesenchymal stem cell source for treating joint pathologies. World J Orthop 2011; 2(6): 43–50

    PubMed Central  PubMed  Google Scholar 

  18. Liu L, Zhao X, Li P, Zhao G, Wang Y, Hu Y, Hou Y. A novel way to isolate MSCs from umbilical cords. Eur J Immunol 2012; 42(8): 2190–2193

    CAS  PubMed  Google Scholar 

  19. Malgieri A, Kantzari E, Patrizi MP, Gambardella S. Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. Int J Clin Exp Med 2010; 3(4): 248–269

    PubMed Central  PubMed  Google Scholar 

  20. Xu LX, Cao YB, Liu ZY, Wu YM, Wang ZH, Yan B, Da WM, Wu XX. Transplantation of haploidentical-hematopoietic stem cells combined with two kind of third part cells for chronic aplastic anemia: one case report. J Exp Hematol (Zhongguo Shi Yan Xue Ye Xue Za Zhi) 2013; 21(6): 1522–1525 (in Chinese)

    Google Scholar 

  21. Gu W, Gu J. Homing mechanism of umbilical cord mesenchymal stem cells. Chin J Tissue Eng Res (Zhongguo Zu Zhi Gong Cheng Yan Jiu) 2013; 17(6): 1135–1140 (in Chinese)

    CAS  Google Scholar 

  22. Li DR, Cai JH. Methods of isolation, expansion, differentiating induction and preservation of human umbilical cord mesenchymal stem cells. Chin Med J (Engl) 2012; 125(24): 4504–4510

    CAS  Google Scholar 

  23. Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 2011; 9(1): 12

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Guo J, Yang J, Cao G, Fan H, Guo C, Ma YE, Qian Y, Chen L, Li X, Chang C. Xenogeneic immunosuppression of human umbilical cord mesenchymal stem cells in a major histocompatibility complex-mismatched allogeneic acute graft-versus-host disease murine model. Eur J Haematol 2011; 87(3): 235–243

    CAS  PubMed  Google Scholar 

  25. Wang D, Chen K, Du WT, Han ZB, Ren H, Chi Y, Yang SG, Bayard F, Zhu D, Han ZC. CD14+ monocytes promote the immunosuppressive effect of humanumbilical cord matrix stem cells. Exp Cell Res 2010; 316(15): 2414–2423

    CAS  PubMed  Google Scholar 

  26. Das M, Sundell IB, Koka PS. Adult mesenchymal stem cells and their potency in the cell-based therapy. J Stem Cells 2013; 8(1): 1–16

    PubMed  Google Scholar 

  27. Atoui R, Shum-Tim D, Chiu RC. Myocardial regenerative therapy: immunologic basis for the potential “universal donor cells”. Ann Thorac Surg 2008; 86(1): 327–334

    PubMed  Google Scholar 

  28. Patel DM, Shah J, Srivastava AS. Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem Cells Int 2013; 2013: 496218

    PubMed Central  PubMed  Google Scholar 

  29. Liu GY, Xu Y, Li Y, Wang LH, Liu YJ, Zhu D. Secreted galectin-3 as a possible biomarker for the immunomodulatory potential of human umbilical cord mesenchymal stromal cells. Cytotherapy 2013; 15(10): 1208–1217

    CAS  PubMed  Google Scholar 

  30. Wang D, Ji YR, Chen K, Du WT, Yang ZX, Han ZB, Chi Y, Liang L, Bayard F, Han ZC. IL-6 production stimulated by CD14(+) monocytes-paracrined IL-1β does not contribute to the immunosuppressive activity of human umbilical cord mesenchymal stem cells. Cell Physiol Biochem 2012; 29(3–4): 551–560

    CAS  PubMed  Google Scholar 

  31. Wu CC, Wu TC, Liu FL, Sytwu HK, Chang DM. TNF-α inhibitor reverse the effects of human umbilical cord-derived stem cells on experimental arthritis by increasing immunosuppression. Cell Immunol 2012; 273(1): 30–40

    CAS  PubMed  Google Scholar 

  32. Liu GY, Xu Y, Li Y, Wang LH, Liu YJ, Zhu D. Secreted galectin-3 as a possible biomarker for the immunomodulatory potential of human umbilical cord mesenchymal stromal cells. Cytotherapy 2013; 15(10): 1208–1217

    CAS  PubMed  Google Scholar 

  33. Greco SJ, Rameshwar P. Mesenchymal stem cells in drug/gene delivery: implications for cell therapy. Ther Deliv 2012; 3(8): 997–1004

    CAS  PubMed  Google Scholar 

  34. Fong CY, Chak LL, Biswas A, Tan JH, Gauthaman K, Chan WK, Bongso A. Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev 2011; 7(1): 1–16

    CAS  PubMed  Google Scholar 

  35. Liu X, Ye R, Yan T, Yu SP, Wei L, Xu G, Fan X, Jiang Y, Stetler RA, Liu G, Chen J. Cell based therapies for ischemic stroke: from basic science to bedside. Prog Neurobiol 2014; 115: 92–115

    PubMed Central  PubMed  Google Scholar 

  36. Liao W, Xie J, Zhong J, Liu Y, Du L, Zhou B, Xu J, Liu P, Yang S, Wang J, Han Z, Han ZC. Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation 2009; 87(3): 350–359

    PubMed  Google Scholar 

  37. Lin YC, Ko TL, Shih YH, Lin MY, Fu TW, Hsiao HS, Hsu JY, Fu YS. Human umbilical mesenchymal stem cells promote recovery after ischemic stroke. Stroke 2011; 42(7): 2045–2053

    PubMed  Google Scholar 

  38. Weise G, Lorenz M, Pösel C, Maria Riegelsberger U, Störbeck V, Kamprad M, Kranz A, Wagner DC, Boltze J. Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats. J Cereb Blood Flow Metab 2014; 34(1): e1–e9

    PubMed Central  PubMed  Google Scholar 

  39. Pellegrini L, Bennis Y, Guillet B, Velly L, Bruder N, Pisano P. Cell therapy for stroke: from myth to reality. Rev Neurol (Paris) 2013; 169(4): 291–306 (in French)

    CAS  Google Scholar 

  40. Lindvall O, Kokaia Z.iStem cell research in stroke: how far from the clinic? Stroke 2011; 42(8): 2369–2375

    PubMed  Google Scholar 

  41. Xia G, Hong X, Chen X, Lan F, Zhang G, Liao L. Intracerebral transplantation of mesenchymal stem cells derived from human umbilical cord blood alleviates hypoxic ischemic brain injury in rat neonates. J Perinat Med 2010; 38(2): 215–221

    PubMed  Google Scholar 

  42. Messerli M, Wagner A, Sager R, Mueller M, Baumann M, Surbek DV, Schoeberlein A. Stem cells from umbilical cord Wharton’s jelly from preterm birth have neuroglial differentiation potential. Reprod Sci 2013; 20(12): 1455–1464

    PubMed Central  PubMed  Google Scholar 

  43. Yan M, Sun M, Zhou Y, Wang W, He Z, Tang D, Lu S, Wang X, Li S, Wang W, Li H. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopamine neurons mediated by the Lmx1a and neurturin in vitro: potential therapeutic application for Parkinson’s disease in a rhesus monkey model. PLoS ONE 2013; 8(5): e64000

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Lees JS, Sena ES, Egan KJ, Antonic A, Koblar SA, Howells DW, Macleod MR. Stem cell-based therapy for experimental stroke: a systematic review and meta-analysis. Int J Stroke 2012; 7(7): 582–588

    PubMed  Google Scholar 

  45. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells 2006; 24(3): 781–792

    CAS  PubMed  Google Scholar 

  46. Liu XS, Chopp M, Wang XL, Zhang L, Hozeska-Solgot A, Tang T, Kassis H, Zhang RL, Chen C, Xu J, Zhang ZG. MicroRNA-17-92 cluster mediates the proliferation and survival of neural progenitor cells after stroke. J Biol Chem 2013; 288(18): 12478–12488

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Tornero D, Wattananit S, Grønning Madsen M, Koch P, Wood J, Tatarishvili J, Mine Y, Ge R, Monni E, Devaraju K, Hevner RF, Brüstle O, Lindvall O, Kokaia Z. Human induced pluripotent stem cell-derived cortical neurons integrate in stroke-injured cortex and improve functional recovery. Brain 2013; 136(12): 3561–3577

    PubMed  Google Scholar 

  48. Martí-Fàbregas J, Romaguera-Ros M, Gómez-Pinedo U, Martínez-Ramírez S, Jiménez-Xarrié E, Marín R, Martí-Vilalta JL, García-Verdugo JM. Proliferation in the human ipsilateral subventricular zone after ischemic stroke. Neurology 2010; 74(5): 357–365

    PubMed  Google Scholar 

  49. Jin K, Wang X, Xie L, Mao XO, Greenberg DA. Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in mice. Proc Natl Acad Sci USA 2010; 107(17): 7993–7998

    PubMed Central  CAS  PubMed  Google Scholar 

  50. Raber J, Fan Y, Matsumori Y, Liu Z, Weinstein PR, Fike JR, Liu J. Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits. Ann Neurol 2004; 55(3): 381–389

    PubMed  Google Scholar 

  51. Dibajnia P, Morshead CM. Role of neural precursor cells in promoting repair following stroke. Acta Pharmacol Sin 2013; 34(1): 78–90

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Liu C, Sun J. Potential application of hydrolyzed fish collagen for inducing the multidirectional differentiation of rat bone marrow mesenchymal stem cells. Biomacromolecules 2014; 15(1): 436–443

    CAS  PubMed  Google Scholar 

  53. Kim SS, Yoo SW, Park TS, Ahn SC, Jeong HS, Kim JW, Chang DY, Cho KG, Kim SU, Huh Y, Lee JE, Lee SY, Lee YD, Suh-Kim H. Neural induction with neurogenin1 increases the therapeutic effects of mesenchymal stem cells in the ischemic brain. Stem Cells 2008; 26(9): 2217–2228

    PubMed  Google Scholar 

  54. Seo JH, Cho SR. Neurorestoration induced by mesenchymal stem cells: potential therapeutic mechanisms for clinical trials. Yonsei Med J 2012; 53(6): 1059–1067

    PubMed Central  PubMed  Google Scholar 

  55. Xu W, Wang X, Xu G, Guo J. Light-induced retinal injury enhanced neurotrophins secretion and neurotrophic effect of mesenchymal stem cells in vitro. Arq Bras Oftalmol 2013; 76(2): 105–110

    PubMed  Google Scholar 

  56. Choi M, Lee HS, Naidansaren P, Kim HK, O E, Cha JH, Ahn HY, Yang PI, Shin JC, Joe YA. Proangiogenic features of Wharton’s jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels. Int J Biochem Cell Biol 2013; 45(3): 560–570

    CAS  PubMed  Google Scholar 

  57. Alder J, Kramer BC, Hoskin C, Thakker-Varia S. Brain-derived neurotrophic factor produced by human umbilical tissue-derived cells is required for its effect on hippocampal dendritic differentiation. Dev Neurobiol 2012; 72(6): 755–765

    CAS  PubMed  Google Scholar 

  58. Ribeiro CA, Fraga JS, Grãos M, Neves NM, Reis RL, Gimble JM, Sousa N, Salgado AJ. The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations. Stem Cell Res Ther 2012; 3(3): 18

    PubMed Central  CAS  PubMed  Google Scholar 

  59. Qu R, Li Y, Gao Q, Shen L, Zhang J, Liu Z, Chen X, Chopp M. Neurotrophic and growth factor gene expression profiling of mouse bone marrow stromal cells induced by ischemic brain extracts. Neuropathology 2007; 27(4): 355–363

    PubMed Central  PubMed  Google Scholar 

  60. Verina T, Fatemi A, Johnston MV, Comi AM. Pluripotent possibilities: human umbilical cord blood cell treatment after neonatal brain injury. Pediatr Neurol 2013; 48(5): 346–354

    PubMed  Google Scholar 

  61. Liu XL, Zhang W, Tang SJ. Intracranial transplantation of human adipose-derived stem cells promotes the expression of neurotrophic factors and nerve repair in rats of cerebral ischemia-reperfusion injury. Int J Clin Exp Pathol 2014; 7(1): 174–183

    PubMed Central  PubMed  Google Scholar 

  62. Petrova ES. The use of stem cells to stimulate regeneration of damaged nerve. Tsitologiia 2012; 54(7): 525–540 (in Russian)

    CAS  PubMed  Google Scholar 

  63. Liu Z, Huang D, Zhang M, Chen Z, Jin J, Huang S, Zhang Z, Wang Z, Chen L, Chen L, Xu Y. Cocaine- and amphetamine-regulated transcript promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells into neural cells. BMC Neurosci 2011; 12: 67

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Wang LL, Chen D, Lee J, Gu X, Alaaeddine G, Li J, Wei L, Yu SP. Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice. PLoS ONE 2014; 9(2): e87284

    PubMed Central  PubMed  Google Scholar 

  65. Liu XL, Zhang W, Tang SJ. Intracranial transplantation of human adipose-derived stem cells promotes the expression of neurotrophic factors and nerve repair in rats of cerebral ischemia-reperfusion injury. Int J Clin Exp Pathol 2014; 7(1): 174–183

    PubMed Central  PubMed  Google Scholar 

  66. Akimoto K, Kimura K, Nagano M, Takano S, To’a Salazar G, Yamashita T, Ohneda O. Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote, glioblastoma multiforme proliferation. Stem Cells Dev 2013; 22(9): 1370–1386

    PubMed Central  CAS  PubMed  Google Scholar 

  67. Zhai XD, Chen ZY, Leng XF, Wang YJ, Chen Lu, Jiang S. Treat flap ischemia-reperfusion injury by local transplanting human umbilical cord mesenchymal stem cells. Chin J Plast Surg (Zhonghua Zheng Xing Wai Ke Za Zhi) 2012; 28(3): 203–207 (in Chinese)

    Google Scholar 

  68. Kim WR, Sun W. Programmed cell death during postnatal development of the rodent nervous system. Dev Growth Differ 2011; 53(2): 225–235

    PubMed  Google Scholar 

  69. Lin WY, Chang YC, Ho CJ, Huang CC. Ischemic preconditioning reduces neurovascular damage after hypoxia-ischemia via the cellular inhibitor of apoptosis 1 in neonatal brain. Stroke 2013; 44(1): 162–169

    PubMed  Google Scholar 

  70. Huang W, Mo X, Qin C, Zheng J, Liang Z, Zhang C. Transplantation of differentiated bone marrow stromal cells promotes motor functional recovery in rats with stroke. Neurol Res 2013; 35(3): 320–328

    PubMed  Google Scholar 

  71. Scheibe F, Klein O, Klose J, Priller J. Mesenchymal stromal cells rescue cortical neurons from apoptotic cell death in an in vitro model of cerebral ischemia. Cell Mol Neurobiol 2012; 32(4): 567–576

    CAS  PubMed  Google Scholar 

  72. Scuteri A, Ravasi M, Pasini S, Bossi M, Tredici G. Mesenchymal stem cells support dorsal root ganglion neurons survival by inhibiting the metalloproteinase pathway. Neuroscience 2011; 172: 12–19

    CAS  PubMed  Google Scholar 

  73. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 2010; 87(5): 779–789

    PubMed Central  CAS  PubMed  Google Scholar 

  74. Carroll J. Human cord blood for the hypoxic-ischemic neonate. Pediatr Res 2012; 71(4 Pt 2): 459–463

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Womble TA, Green S, Shahaduzzaman M, Grieco J, Sanberg PR, Pennypacker KR, Willing AE. Monocytes are essential for the neuroprotective effect of human cord blood cells following middle cerebral artery occlusion in rat. Mol Cell Neurosci 2014; 59: 76–84

    CAS  PubMed  Google Scholar 

  76. Bickels J, Weinstein T, Robinson D, Nevo Z. Common skeletal growth retardation disorders resulting from abnormalities within the mesenchymal stem cells reservoirs in the epiphyseal organs pertaining to the long bones. J Pediatr Endocrinol Metab 2010; 23(11): 1107–1122

    PubMed  Google Scholar 

  77. Leonardo CC, Hall AA, Collier LA, Ajmo CT Jr, Willing AE, Pennypacker KR. Human umbilical cord blood cell therapy blocks the morphological change and recruitment of CD11b-expressing, isolectin-binding proinflammatory cells after middle cerebral artery occlusion. J Neurosci Res 2010; 88(6): 1213–1222

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Seo JH, Jang IK, Kim HB, Yang MS, Lee JE, Kim HE, Eom YW, Lee DH, Yu JH, Kim JY, Kim HO, Cho SR. Immunomodulation from intravenous transplantation of mesenchymal stem cells promotes functional recovery in spinal cord injured rats. Cell Med 2011; 2(2): 55–67

    Google Scholar 

  79. Eckert MA, Vu Q, Xie K, Yu J, Liao W, Cramer SC, Zhao W. Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke. J Cereb Blood Flow Metab 2013; 33(9): 1322–1334

    PubMed Central  PubMed  Google Scholar 

  80. Petrie Aronin CE, Tuan RS. Therapeutic potential of the immunomodulatory activities of adult mesenchymal stem cells. Birth Defects Res C Embryo Today 2010; 90(1): 67–74

    CAS  PubMed  Google Scholar 

  81. Carroll JE, Mays RW. Update on stem cell therapy for cerebral palsy. Expert Opin Biol Ther 2011; 11(4): 463–471

    PubMed Central  PubMed  Google Scholar 

  82. Wang D, Wang S, Shi C. Update on cancer related issues of mesenchymal stem cell-based therapies. Curr Stem Cell Res Ther 2012; 7(5): 370–380

    CAS  PubMed  Google Scholar 

  83. Lua I, James D, Wang J, Wang KS, Asahina K. Mesodermal mesenchymal cells give rise to myofibroblasts, but not epithelial cells, in mouse liver injury. Hepatology 2014; 60(1): 311–322

    CAS  PubMed  Google Scholar 

  84. Lin JT, Wang JY, Chen MK, Chen HC, Chang TH, Su BW, Chang PJ. Colon cancer mesenchymal stem cells modulate the tumorigenicity of colon cancer through interleukin 6. Exp Cell Res 2013; 319(14): 2216–2229

    CAS  PubMed  Google Scholar 

  85. Rameshwar P. Would cancer stem cells affect the future investment in stem cell therapy. World J Exp Med 2012; 2(2): 26–29

    PubMed Central  PubMed  Google Scholar 

  86. Lin G, Yang R, Banie L, Wang G, Ning H, Li LC, Lue TF, Lin CS. Effects of transplantation of adipose tissue-derived stem cells on prostate tumor. Prostate 2010; 70(10): 1066–1073

    PubMed Central  PubMed  Google Scholar 

  87. Honmou O, Houkin K, Matsunaga T, Niitsu Y, Ishiai S, Onodera R, Waxman SG, Kocsis JD. Intravenous administration of auto serumexpanded autologous mesenchymal stem cells in stroke. Brain 2011; 134(6): 1790–1807

    PubMed Central  PubMed  Google Scholar 

  88. Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY; STARTING collaborators. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 2010; 28(6): 1099–1106

    PubMed  Google Scholar 

  89. Chen GH, Yang T, Tian H, Qiao M, Liu HW, Fu CC, Miao M, Jin ZM, Tang XW, Han Y, He GS, Zhang XH, Ma X, Chen F, Hu XH, Xue SL, Wang Y, Qiu HY, Sun AN, Chen ZZ, Wu DP. Clinical study of umbilical cord-derived mesenchymal stem cells for treatment of nineteen patients with steroid-resistant severe acute graft-versus-host disease. Chin J Hematol (Zhonghua Xue Ye Xue Za Zhi) 2012; 33(4): 303–306 (in Chinese)

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Post-Graduate School, Hunan University of Traditional Chinese Medicine, Changsha, 410208, China

    Yingchen Li & Qilai Cheng

  2. Department of Neurology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, 410007, China

    Guoheng Hu

Authors
  1. Yingchen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guoheng Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qilai Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guoheng Hu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Hu, G. & Cheng, Q. Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges. Front. Med. 9, 20–29 (2015). https://doi.org/10.1007/s11684-014-0371-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-014-0371-x

Keywords

Search

Navigation