诱导多功能干细胞治疗缺血性卒中：诱惑与现实

摘要/Abstract

摘要：

诱导多能干细胞（induced pluripotent stem cells，iPSC）由特定的转录因子转录已分化的体细胞而来，在生物学功能方面与胚胎干细胞（embryonic stem cell，ESC）类似。实际应用中，iPSC在细胞来源、免疫原性和医学伦理等方面面临较少的困境，从而为疾病提供更多的临床治疗策略。在治疗方面与普通干细胞相比，具有更多的优越性，但iPSC的致瘤性、诱导率低等问题，仍有待进一步解决。本文将重点探讨iPSC治疗缺血性卒中的研究现状、发展制约及未来展望。

文章导读： 本文重点介绍了iPSC治疗缺血性卒中的进展和不足，对基础和临床研究有一定的指导意义。

关键词: 缺血性卒中; 诱导多能干细胞; 治疗

Abstract:

introducing the specific transcription factors into adult cells, and similar to embryonic stem cells in biological function. And iPSC in the use of the cell source, immunogenicity and medical ethics, and so on to face less difficult, so as to provide more clinical treatment strategies for the disease. Compared with the common stem cells in treatment, it has more advantages, but the iPSC of the tumor and the induction rate is low. This article will focus on the research status, development and future prospect of iPSC in treating ischemic stroke.

Key words: Ischemic stroke; Induced pluripotent stem cells; Treatment

刘宇恒，许治强，梁燕玲，李斯颖，林永强. 诱导多功能干细胞治疗缺血性卒中：诱惑与现实[J]. 中国卒中杂志, 2015, 10(10): 902-905.

LIU Yu-Heng, XU Zhi-Qiang, LIANG Yan-Ling, et al.. Inducible Pluripotent Stem Cells for the Treatment of Ischemic Stroke: Entice and Current Status[J]. Chinese Journal of Stroke, 2015, 10(10): 902-905.

参考文献

1 中华医学会神经病学分会脑血管病学组缺血性卒中

二级预防指南撰写组. 中国缺血性卒中和短暂性脑缺

血发作二级预防指南2010[J]. 中华神经科杂志, 2010,

43:154-160.

2 Hughes PA. Comprehensive care of adults with acute

ischemic stroke[J]. Crit Care Nurs Clin North Am,

2011, 23:661-675.

3 Jauch EC, Saver JL, Adams HP, et al. Guidelines for

the early management of patients with acute ischemic

stroke:a guideline for healthcare professionals from

the American Heart Association/American Stroke

Association[J]. Stroke, 2013, 44:870-947.

4 Wang Y, Liao X, Zhao X, et al. Using recombinant

tissue plasminogen activator to treat acute ischemic

stroke in China:analysis of the results from the

Chinese National Stroke Registry (CNSR)[J]. Stroke,

2011, 42:1658-1644. .

5 Abrahams JM, Gokhan S, Flamm ES, et al. De

novo neurogenesis and acute stroke:are exogenous

stem cells really necessary?[J]. Neurosurgery, 2004,

54:150-156.

6 Amabile G, Meissner A. Induced pluripotent stem

cells:current progress and potential for regenerative

medicine[J]. Trends Mol Med, 2009, 15:59-68.

7 Takahashi K, Yamanaka S. Induction of pluripotent

stem cells from mouse embryonic and adult fibroblast

cultures by defined factors[J]. Cell, 2006, 126:663-676.

8 Takahashi K, Tanabe K, Ohnuki M, et al. Induction of

pluripotent stem cells from adult human fibroblasts by

defined factors[J]. Cell, 2007, 131:861-872.

9 Chen J, Shehadah A, Pal A, et al. Neuroprotective

effect of human placenta-derived cell treatment of

stroke in rats[J]. Cell Transplant, 2013, 22:871-879.

10 Ma S, Zhong D, Chen H, et a1. The immunomodulatory

effect of bone marrow stromal cells(BMSCs)on

interleukin(IL)-23/IL-17-mediated ischemic stroke in

mice[J]. J Neuroimmunol, 2013, 257:28-35.

11 Ishizaka S, Horie N, Satoh K, et a1. Intra-arterial

cell transplantation provides timing-dependent cell

distribution and functional recovery after stroke[J].

Stroke, 2013, 44:720-726.

12 Bao X, Wei J, Feng M, et al. Transplantation of

human bone marrow-derived mesenchymal stem

cells promotes behavioral recovery and endogenous

neurogenesis after cerebral ischemia in rats[J]. Brain

Res, 2011, 1367:103-113.

13 Kameda M, Shingo T, Takahashi K, et al. Adult neural

stem and progenitor cells modified to secrete GDNF

can protect, migrate and integrate after intracerebral

transplantation in rats with transient forebrainischemia[J]. Eur J Neurosci, 2007, 26:1462-1478.

14 刘建民, 毛伯镛. 神经干细胞与血管内皮祖细胞共移

植治疗缺血性脑卒中的研究进展[J]. 中国修复重建外

科杂志, 2007, 21:204-208.

15 Chen SJ, Chang CM, Tsai SK, et al. Functional

improvement of focal cerebral ischemia injury by

subdural transplantation of induced pluripotent

stem cells with fibrin glue[J]. Stem Cells Dev, 2010,

19:1757-1767.

16 Oki K, Tatarishvili J, Wood J, et al. Human-induced

pluripotent stem cells form functional neurons and

improve recovery after grafting in stroke-damaged

brain[J]. Stem Cells, 2012, 30:1120-1133.

17 Gomi M, Takagi Y, Morizane A, et al. Functional

recovery of the mur ine brain ischemia model

using humaninduced pluripotent stem cell-derived

telencephalic progenitors[J]. Brain Res, 2012,

1459:52-60.

18 Jiang M, Lv L, Ji H, et al. Induction of pluripotent

stem cells transplantation therapy for ischemic

stroke[J]. Mol Cell Biochem, 2011, 354:67-75.

19 Chang DJ, Lee N, Park IH, et al. Therapeutic

potential of human induced pluripotent stem cells

in experimental stroke[J]. Cell Transplant, 2012,

22:1427-1440.

20 Polentes J, Jendelova P, Cailleret M, et al. Human

induced pluripotent stem cells improve stroke outcome

and reduce secondary degeneration in the recipient

brain[J]. Cell Transplant, 2012, 21:2587-2602.

21 Wang J, Chao F, Han F. PET demonstrates functional

recovery after transplantation of induced pluripotent

stem cells in a rat model of cerebral ischemic injury[J].

J Nucl Med, 2013, 54:785-792.22 Kawai H, Yamashita T, Ohta Y, et al. Tridermal

tumorigenesis of induced pluripotent stem cells

transplanted in ischemic brain[J]. J Cereb Blood Flow

Metab, 2010, 30:1487-1493.

23 Jensen MB, Yan H, Krishnaney-Davison R, et al.

Survival and differentiation of transplanted neural

stem cells derived from human induced pluripotent

stem cells i n a rat st roke model[J ]. J St roke

Cerebrovasc Dis, 2013, 22:304-308.

24 Anokye-Danso F, Trivedi CM, Juhr D, et al. Highly

effieient miRNA-mediated reprogramming of mouse

and human somatic cells to pluripotency[J]. Cell Stem

Cell, 2011, 8:376-388.

25 Xu X, Wang Q, Long Y, et a1. Stress-mediated p38

activation promotes somatic cell mpmgramming[J].

Cell Res, 2013, 23:131-141.

26 Yamanaka S. Safer way to make human stem-like

cells revealed[J]. Nature, 2007, 450:450.

27 Nakagawa M, Takizawa N, Narita M, et a1. Promotion

of direct reprogramming by transformation--deficient

Myc[J]. Proc Natl Acad Sci USA, 20l0, 107:14152-

14157.

28 Rhee YH, Ko JY, Chang MY, et a1. Protein-based

human iPS cells efficiently generate functional

dopamine neurons and can t reat a rat model

of Parkinson disease[J ]. J Cl i n Invest , 2011,

121:2326-2335.

29 Zhao T, Zhang ZN, Rong Z, et al. Immunogenicity

of induced pluripotent stem cells[J]. Nature, 2011,

474:212-215.

30 Lu X, Zhao T. Clinical therapy using iPSCs:hopes and

challenges[J]. Genomics Proteomics Bioinformatics,

2013, 11:294-298.

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