脐带血移植治疗缺氧缺血性脑损伤和缺血性脑卒中的研究进展

摘要/Abstract

摘要： 人脐带血(human umbilical cord blood,HUCB)富含丰富的未成熟干细胞,这些干细胞具有修复受损组织的潜能。HUCB干细胞移植在动物模型中可以产生多种作用:神经保护、神经再生、抗炎、血管再生等作用。目前HUCB干细胞移植已被用于治疗血液系统疾病,其还可以用于神经系统疾病,并已在基础研究方面取得较大进展。本文简要讨论HUCB移植的治疗机制及在缺氧缺血性脑损伤和缺血性脑卒中的研究进展。

关键词: 脐带血, 细胞移植, 缺氧缺血性脑损伤, 缺血性脑卒中

Abstract: Human umbilical cord blood (HUCB) is abundant with immature stem cells. These stem cells have the potential to repair damaged tissue. HUCB transplantation can produce various effects in animal models such as neuroprotection, nerve regeneration, anti-inflammatory, and vascular regeneration effect.At present, it is generally acknowledged that HUCB stem cells transplantation plays an important role in the treatment of blood diseases, but it can also be applied to neurological disorders, and has made great progress on the basis of clinical trials. This review briefly expounds the therapeutic mechanism of HUCB transplantation and research in hypoxic-ischemic brain injury and ischemic stroke.

Key words: umbilical cord blood, cell transplantation, hypoxic-ischemic brain injury, ischemic stroke

中图分类号:

R743

叶壮, 李志奇. 脐带血移植治疗缺氧缺血性脑损伤和缺血性脑卒中的研究进展[J]. 中国临床药理学与治疗学, 2015, 20(4): 450-454.

YE Zhuang , LI Zhi-qi. Progress in umbilical cord blood transplantation for hypoxic-ischemic brain injury and ischemic stroke[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(4): 450-454.

参考文献

[1] Kurtzberg J, Laughlin M, Graham ML, et al. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients[J]. N Engl J Med,1996,335(3):157-166.
[2] Herranz AS, Gonzalo-Gobernado R, Reimers D, et al. Applications of human umbilical cord blood cells in central nervous system regeneration[J]. Curr Stem Cell Res Ther,2010,5(1): 17-22.
[3] 唐文,蒋明德.干细胞移植术治疗肝硬化的临床应用[J].临床肝胆病杂志,2012,28(10):735-737.
[4] Hussain I, Magd SA, Eremin O, et al. New approach to isolate mesenchymal stem cell (MSC) from human umbilical cord blood[J]. Cell Biol Int,2012,36(7): 595-600.
[5] Goodwin HS, Bicknese AR, Chien SN, et al. Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers[J]. Biol Blood Marrow Transplant,2001,7(11): 581-588.
[6] Kögler G, Sensken S, Airey JA, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential[J]. J Exp Med,2004,200(2): 123-135.
[7] Neuhoff S, Moers J, Rieks M, et al. Proliferation, differentiation, and cytokine secretion of human umbilical cord blood-derived mononuclear cells in vitro[J]. Exp Hematol,2007,35(7): 1119-1131.
[8] Newman MB, Willing AE, Manresa JJ, et al. Cytokines produced by cultured human umbilical cord blood (HUCB) cells: implications for brain repair[J]. Exp Neurol,2006,199(1):201-208.
[9] Yang JP, Liu HJ, Yang H, et al. Therapeutic time window for the neuroprotective effects of NGF when administered after focal cerebral ischemia[J]. Neurol Sci,2011,32(3): 433-441.
[10]Rowe DD, Leonardo CC, Recio JA, et al. Human umbilical cord blood cells protect oligo dendrocytes from brain ischemia through Akt signal transduction[J]. J Biol Chem,2012,287(6): 4177-4187.
[11]Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model[J]. J Clin Invest,2004,114(3): 330-338.
[12]Taguchi A, Matsuyama T, Moriwaki H, et al. Circulating CD34-positive cells provide an index of cerebrovascular function[J]. Circulation,2004,109(24): 2972-2975.
[13]朱琳琳,谢向荣,张娟,等.急性心肌梗死患者自体骨髓干细胞移植治疗效果随访[J].中国临床药理学与治疗学,2013,18(06):674-679.
[14]Ding DC, Shyu WC, Chiang MF, et al. Enhancement of neuroplasticity through upregulation of beta1-integrin in human umbilical cord-derived stromal cell implanted stroke model[J]. Neurobiol Dis,2007,27(3): 339-353.
[15]Zacharek A, Chen J, Cui X, et al. Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke[J]. J Cereb Blood Flow Metab,2007,27(10): 1684-1691.
[16]Rosenkranz K, Kumbruch S, Tenbusch M, et al. Transplantation of human umbilical cord blood cells mediated beneficial effects on apoptosis, angiogenesis and neuronal survival after hypoxic-ischemic brain injury in rats[J]. Cell Tissue Res,2012,348(3): 429-438.
[17]Lakhan SE, Kirchgessner A, Hofer M, et al. Inflammatory mechanisms in ischemic stroke: therapeutic approaches[J]. J Transl Med,2009,7: 97.
[18]Offner H, Subramanian S, Parker SM, et al. Experimental stroke induces massive, rapid activation of the peripheral immune system[J]. J Cereb Blood Flow Metab,2006,26(5): 654-665.
[19]Xin J, Wainwright DA, Mesnard NA, et al. IL-10 within the CNS is necessary for CD4+ T cells to mediate neuroprotection[J]. Brain Behav Immun,2011,25(5): 820-829.
[20]Zhou J, Huang WQ, Li C, et al. Intestinal ischemia/reperfusion enhances microglial activation and induces cerebral injury and memory dysfunction in rats[J].Crit Care Med,2012,40(8): 2438-2448.
[21]Newcomb JD, Ajmo CT Jr, Sanberg CD, et al. Timing of cord blood treatment after experimental stroke determines therapeutic efficacy[J]. Cell Transplant,2006,15(3): 213-223.
[22]Lai MC, Yang SN. Perinatal hypoxic-ischemic encephalopathy[J]. J Biomed Biotechnol,2011.
[23]LEVINE S. Anoxic-ischemic encephalopathy in rats[J]. Am J Pathol,1960,36(1): 1-17.
[24]Rice JE, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat[J]. Ann Neurol,1981,9(2): 131-141.
[25]Meier C, Middelanis J, Wasielewski B, et al. Spastic Paresis After Perinatal Brain Damage in Rats Is Reduced by Human Cord Blood Mononuclear Cells[J]. Pediatr Res,2006,59(2): 244-249.
[26]Pimentel-Coelho PM, Magalhães ES, Lopes LM, et al. Human cord blood transplantation in a neonatal rat model of hypoxic-ischemic brain damage:functional outcome related to neuroprotection in the striatum[J].Stem Cells Dev,2010,19(3): 351-358.
[27]Yasuhara T, Hara K, Maki M, et al. Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxicischaemic rats with human umbilical cord blood grafts[J]. J Cell Mol,2010,14(4): 914-921.
[28]Geissler M, Dinse HR, Neuhoff S, et al. Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex[J]. PLoS One,2011,6(6): e20194.
[29]de Paula S, Vitola AS, Greggio S, et al. Hemisphericbrain injury and behavioral deficits induced by severe neonatal hypoxia-ischemia in rats are not attenuated by intravenous administration of human umbilical cord blood cells[J]. Pediatr Res,2009,65(5): 631-635.
[30]屠文娟,张琴芬,张新化,等. 人脐带间充质干细胞对新生大鼠缺氧缺血性脑损伤的神经修复作用[J].中国新生儿科杂志,2013,28(6):404-412.
[31]黄会芝,温晓红,刘慧,等. 人脐血单核细胞移植对缺氧缺血性脑损伤新生大鼠远期神经行为学功能发育的影响[J].中华儿科杂志,2013,51(6):460-466.
[32]Chen J, Sanberg PR, Li Y, et al. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats[J].Stroke,2001,32(11): 2682-2688.
[33]Vendrame M, Cassady J, Newcomb J, et al. Infusion of human umbilical cord blood cells in a rat model of stroke dose dependently rescues behavioral deficits and reduces infarct volume[J]. Stroke,2004,35(10): 2390-2395.
[34]Willing AE, Lixian J, Milliken M, et al. Intravenous Versus Intrastriatal Cord Blood Administration in a Rodent Model of Stroke[J].J Neurosci Res,2003,73(3): 296-307.
[35]Borlongan CV, Hadman M, Sanberg CD, et al. Central Nervous System Entry of Peripherally Injected Umbilical Cord Blood Cells Is Not Required for Neuroprotection[J]. Stroke,2004,35(10):2385-2389.
[36]Lim JY, Jeong CH, Jun JA, et al. Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral isch- emia[J]. Stem Cell Res Ther,2011,2(5): 38.