J.Neurosci.：研究发现干细胞移植到受损视网膜的关键分子
哈佛医学院Schepens 眼科研究所的研究人员发现制造视网膜、脊髓和其它中央神经系统的关键。这项研究发现由干细胞所诱引的MMP-2，可以分解受损的视网膜外表面之屏障，并允许健康的捐赠细胞进入受赠者残余的组织中。
研究作者Michael Young表示，这是一项非常重大的发现，将有助于进行视网膜移植和恢复患者视力。移植捐赠者的感光受体比比移植干细胞更有利，因为这些视网膜移植物中，包含产生清晰的视觉所需的完全组织化之细胞。
成年哺乳动物包括人类的中央神经系统组织再生能力非常有限。因为会形成神经胶质疤(glial scar) 神经胶质疤是神经轴突生长的障壁，因此会阻止中枢神经系统中的神经轴突的再生，保护受损的视网膜或其它神经组织免受进一步损伤。这个密集的伤痕组织会阻挡外来细胞，所以移植相当困难。
因此研究人员相信，如果他们可以辨认和利用使干细胞可进入受损视网膜的关键分子，就可以改进非干细胞细胞移植的成功率。
这项研究报告发表于这一期4月25 日出刊的Journal of Neuroscience中，不仅为视网膜疾病的患者提供佳音，也可以造福脊髓受损和神经退化性疾病如帕金森氏症和阿兹海默症患者。
（编译/姜欣慧） (资料来源 : biocompare)
原始出处:
The Journal of Neuroscience, April 25, 2007, 27(17):4499-4506; doi:10.1523/JNEUROSCI.0200-07.2007
CNS Progenitor Cells Promote a Permissive Environment for Neurite Outgrowth via a Matrix Metalloproteinase-2-Dependent Mechanism
Yiqin Zhang,1 Henry J. Klassen,2 Budd A. Tucker,1 Maria-Thereza R. Perez,3 and Michael J. Young1
1Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, 2Stem Cell Research, Children's Hospital of Orange Country, Orange, California 92868, and 3Wallenberg Retina Center, Department of Ophthalmology, Lund University, SE-22100 Lund, Sweden
Correspondence should be addressed to Michael J. Young, Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114. Email: mikey@vision.eri.harvard.edu
Transplantation of progenitor cells to the CNS has shown promise in neuronal and glial replacement and as a means of rescuing host neurons from apoptosis. Here we examined the effect of progenitor grafts on neurite extension in the degenerating retina of rd1 (retinal degeneration 1) mice. Transplantation of retinal progenitor cells induced increased matrix metalloproteinase-2 (MMP2) secretion, partly from activated glial cells, which was then activated by neuronally expressed MMP14. Active MMP2 resulted in proteolysis of the neurite outgrowth inhibitors CD44 and neurocan in the degenerative retina, allowing significantly increased neurite outgrowth across the border between abutting nondystrophic and rd1 retinas. Progenitor-induced enhancement of outgrowth was abrogated by an MMP inhibitor or by coculture with retinal explants from MMP2–/– mice. This study provides the first identification of an MMP2-dependent mechanism by which exogenous progenitor cells alter the host environment to promote neural regeneration. This suggests a novel therapeutic role for progenitor cells in the treatment of CNS degenerative diseases.
Key words: retina; progenitor cell; cell transplantation; cell migration; neurite outgrowth; MMP-2
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细胞移植专题
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