Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges
Yingchen Li1,Guoheng Hu2,*(),Qilai Cheng1
1. Post-Graduate School, Hunan University of Traditional Chinese Medicine, Changsha 410208, China 2. Department of Neurology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha 410007, China
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.
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
https://doi.org/10.1161/STROKEAHA.110.593129
pmid: 21493915
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
https://doi.org/10.1016/j.abb.2013.02.005
pmid: 23466243
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
https://doi.org/10.1074/jbc.M109.086389
pmid: 20139068
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
https://doi.org/10.1016/j.cell.2006.07.024
pmid: 16904174
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
https://doi.org/10.1126/science.284.5411.143
pmid: 10102814
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
https://doi.org/10.1186/scrt456
pmid: 24887697
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
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
https://doi.org/10.1634/stemcells.2004-0166
pmid: 15671145
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
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
pmid: 23253727
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
https://doi.org/10.1007/s11626-008-9155-4
pmid: 19057971
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)
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
https://doi.org/10.3727/096368910X507204
pmid: 20525429
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
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
https://doi.org/10.5312/wjo.v2.i6.43
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
https://doi.org/10.1002/eji.201142356
pmid: 22585466
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
pmid: 21072260
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)
pmid: 24370041
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)
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
pmid: 23253727
23
Hass R, Kasper C, B?hm 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
https://doi.org/10.1186/1478-811X-9-12
pmid: 21569606
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
https://doi.org/10.1111/j.1600-0609.2011.01635.x
pmid: 21535158
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
https://doi.org/10.1016/j.yexcr.2010.04.018
pmid: 20420825
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
pmid: 24459809
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
https://doi.org/10.1016/j.athoracsur.2008.03.038
pmid: 18573459
28
Patel DM, Shah J, Srivastava AS. Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem Cells Int 2013; 2013: 496218
https://doi.org/10.1155/2013/496218
pmid: 23577036
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
https://doi.org/10.1016/j.jcyt.2013.05.011
pmid: 23850421
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
https://doi.org/10.1159/000338509
pmid: 22508062
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
https://doi.org/10.1016/j.cellimm.2011.11.009
pmid: 22196378
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
https://doi.org/10.1016/j.jcyt.2013.05.011
pmid: 23850421
33
Greco SJ, Rameshwar P. Mesenchymal stem cells in drug/gene delivery: implications for cell therapy. Ther Deliv 2012; 3(8): 997–1004
https://doi.org/10.4155/tde.12.69
pmid: 22946432
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
https://doi.org/10.1007/s12015-010-9166-x
pmid: 20602182
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
https://doi.org/10.1016/j.pneurobio.2013.11.007
pmid: 24333397
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
https://doi.org/10.1097/TP.0b013e318195742e
pmid: 19202439
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
https://doi.org/10.1161/STROKEAHA.110.603621
pmid: 21566227
38
Weise G, Lorenz M, P?sel C, Maria Riegelsberger U, St?rbeck 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
https://doi.org/10.1038/jcbfm.2013.185
pmid: 24169850
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)
https://doi.org/10.1016/j.neurol.2012.08.009
pmid: 23246427
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
https://doi.org/10.1515/jpm.2010.021
pmid: 20121545
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
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
https://doi.org/10.1371/journal.pone.0064000
pmid: 23724014
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
https://doi.org/10.1111/j.1747-4949.2012.00797.x
pmid: 22687044
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
https://doi.org/10.1634/stemcells.2005-0330
pmid: 16223852
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
https://doi.org/10.1074/jbc.M112.449025
pmid: 23511639
47
Tornero D, Wattananit S, Gr?nning 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
https://doi.org/10.1093/brain/awt278
pmid: 24148272
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
https://doi.org/10.1212/WNL.0b013e3181cbccec
pmid: 20054008
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
https://doi.org/10.1073/pnas.1000154107
pmid: 20385829
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
https://doi.org/10.1002/ana.10853
pmid: 14991816
51
Dibajnia P, Morshead CM. Role of neural precursor cells in promoting repair following stroke. Acta Pharmacol Sin 2013; 34(1): 78–90
https://doi.org/10.1038/aps.2012.107
pmid: 23064725
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
https://doi.org/10.1021/bm401780v
pmid: 24359018
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
https://doi.org/10.1634/stemcells.2008-0108
pmid: 18617687
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
https://doi.org/10.3349/ymj.2012.53.6.1059
pmid: 23074102
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
https://doi.org/10.1590/S0004-27492013000200010
pmid: 23828471
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
https://doi.org/10.1016/j.biocel.2012.12.001
pmid: 23246593
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
https://doi.org/10.1002/dneu.20980
pmid: 21954108
58
Ribeiro CA, Fraga JS, Gr?os 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
https://doi.org/10.1186/scrt109
pmid: 22551705
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
https://doi.org/10.1111/j.1440-1789.2007.00792.x
pmid: 17899689
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
https://doi.org/10.1016/j.pediatrneurol.2012.10.010
pmid: 23583051
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
pmid: 24427337
62
Petrova ES. The use of stem cells to stimulate regeneration of damaged nerve. Tsitologiia 2012; 54(7): 525–540 (in Russian)
pmid: 23074855
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
https://doi.org/10.1186/1471-2202-12-67
pmid: 21756347
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
https://doi.org/10.1371/journal.pone.0087284
pmid: 24503654
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
pmid: 24427337
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
https://doi.org/10.1161/STROKEAHA.112.677617
pmid: 23192759
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
https://doi.org/10.1179/1743132812Y.0000000151
pmid: 23485057
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
https://doi.org/10.1007/s10571-012-9798-2
pmid: 22290155
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
https://doi.org/10.1016/j.neuroscience.2010.10.065
pmid: 21044661
73
Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 2010; 87(5): 779–789
https://doi.org/10.1189/jlb.1109766
pmid: 20130219
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
https://doi.org/10.1016/j.mcn.2014.01.004
pmid: 24472845
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
https://doi.org/10.1515/jpem.2010.176
pmid: 21284324
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
pmid: 19998484
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
https://doi.org/10.3727/215517911X582788
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
https://doi.org/10.1038/jcbfm.2013.91
pmid: 23756689
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
https://doi.org/10.1002/bdrc.20174
pmid: 20301222
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
https://doi.org/10.1002/hep.27035
pmid: 24488807
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
https://doi.org/10.1016/j.yexcr.2013.06.003
pmid: 23751564
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
https://doi.org/10.1002/pros.21140
pmid: 20232361
87
Honmou O, Houkin K, Matsunaga T, Niitsu Y, Ishiai S, Onodera R, Waxman SG, Kocsis JD. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain 2011; 134(6): 1790–1807
https://doi.org/10.1093/brain/awr063
pmid: 21493695
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
https://doi.org/10.1002/stem.430
pmid: 20506226
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)
pmid: 22781723