在中枢神经系统中实现稳定的人干细胞植入和存活：再生医学的未来是否需要免疫缺陷？
Achieving stable human stem cell engraftment and survival in the CNS: is the future of regenerative medicine immunodeficient?
机构信息
Sue & Bill Gross Stem Cell Center, 845 Health Science Road, UC Irvine, Irvine, CA 92697-1705, USA.
出版信息
Regen Med. 2011 May;6(3):367-406. doi: 10.2217/rme.11.22.
Abstract
There is potential for a variety of stem cell populations to mediate repair in the diseased or injured CNS; in some cases, this theoretical possibility has already transitioned to clinical safety testing. However, careful consideration of preclinical animal models is essential to provide an appropriate assessment of stem cell safety and efficacy, as well as the basic biological mechanisms of stem cell action. This article examines the lessons learned from early tissue, organ and hematopoietic grafting, the early assumptions of the stem cell and CNS fields with regard to immunoprivilege, and the history of success in stem cell transplantation into the CNS. Finally, we discuss strategies in the selection of animal models to maximize the predictive validity of preclinical safety and efficacy studies.
摘要
各种干细胞群体有可能介导病变或受损中枢神经系统的修复；在某些情况下，这种理论上的可能性已经过渡到临床安全性测试。然而，仔细考虑临床前动物模型对于适当评估干细胞的安全性和有效性以及干细胞作用的基本生物学机制至关重要。本文探讨了从早期组织、器官和造血移植中吸取的教训，干细胞和中枢神经系统领域关于免疫豁免的早期假设，以及将干细胞移植到中枢神经系统中取得成功的历史。最后，我们讨论了选择动物模型的策略，以最大限度地提高临床前安全性和有效性研究的预测有效性。
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本文引用的文献
1
Immunological properties of embryonic and adult stem cells.胚胎和成年干细胞的免疫学特性。
World J Stem Cells. 2010 Jun 26;2(3):50-60. doi: 10.4252/wjsc.v2.i3.50.
2
Evaluating the role of Toll-like receptors in diseases of the central nervous system.评估 Toll 样受体在中枢神经系统疾病中的作用。
Biochem Pharmacol. 2011 Apr 1;81(7):825-37. doi: 10.1016/j.bcp.2011.01.003. Epub 2011 Jan 15.
3
Effects of combinatorial treatment with pituitary adenylate cyclase activating peptide and human mesenchymal stem cells on spinal cord tissue repair.垂体腺苷酸环化酶激活肽与人骨髓间充质干细胞联合治疗对脊髓组织修复的影响。
PLoS One. 2010 Dec 20;5(12):e15299. doi: 10.1371/journal.pone.0015299.
4
Immunogenicity of embryonic stem cell-derived progenitors after transplantation.胚胎干细胞衍生祖细胞移植后的免疫原性。
Curr Opin Organ Transplant. 2011 Feb;16(1):90-5. doi: 10.1097/MOT.0b013e3283424faa.
5
Long-term benefit of human fetal neuronal progenitor cell transplantation in a clinically adapted model after traumatic brain injury.外伤性脑损伤后临床适应模型中人胎儿神经前体细胞移植的长期获益。
J Neurotrauma. 2011 Mar;28(3):401-14. doi: 10.1089/neu.2010.1526.
6
Immunologic and inflammatory reactions to exogenous stem cells implications for experimental studies and clinical trials for myocardial repair.对外源性干细胞的免疫和炎症反应对心肌修复的实验研究和临床试验的影响。
J Am Coll Cardiol. 2010 Nov 16;56(21):1693-700. doi: 10.1016/j.jacc.2010.06.041.
7
Comparative study of methods for administering neural stem/progenitor cells to treat spinal cord injury in mice.比较不同方法向小鼠体内移植神经干细胞/祖细胞治疗脊髓损伤的效果。
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Human fetal neural precursor cells can up-regulate MHC class I and class II expression and elicit CD4 and CD8 T cell proliferation.人胎神经前体细胞可上调 MHC Ⅰ类和Ⅱ类分子的表达并引发 CD4 和 CD8 T 细胞的增殖。
Neurobiol Dis. 2011 Feb;41(2):407-14. doi: 10.1016/j.nbd.2010.10.008. Epub 2010 Oct 16.
9
Synergism of human amnion-derived multipotent progenitor (AMP) cells and a collagen scaffold in promoting brain wound recovery: pre-clinical studies in an experimental model of penetrating ballistic-like brain injury.人羊膜多能祖细胞（AMP 细胞）与胶原支架协同作用促进脑创伤恢复：穿透性弹道样脑损伤实验模型的临床前研究。
Brain Res. 2011 Jan 12;1368:71-81. doi: 10.1016/j.brainres.2010.10.028. Epub 2010 Oct 15.
10
Modulation of the postischemic immune response to improve stroke outcome.调节缺血后免疫反应以改善中风预后。
Stroke. 2010 Oct;41(10 Suppl):S75-8. doi: 10.1161/STROKEAHA.110.592881.
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