THE INFLUENCE OF DONOR AGE ON THE SURVIVAL OF SOLID AND SUSPENSION INTRAPARENCHYMAL HUMAN EMBRYONIC NIGRAL GRAFTS
THE INFLUENCE OF DONOR AGE ON THE SURVIVAL OF SOLID AND SUSPENSION INTRAPARENCHYMAL HUMAN EMBRYONIC NIGRAL GRAFTS
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DOI：
10.1016/0963-6897(94)00048-o
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发表时间：
1995-01-01
影响因子：
3.3
通讯作者：
KORDOWER, JH
中科院分区：
文献类型：
--
作者：
FREEMAN, TB;SANBERG, PR;KORDOWER, JH
在许多物种中，移植物的存活和移植物衍生的行为恢复受到胚胎供体年龄的影响。我们比较了不同胚胎阶段的人胚胎中脑多巴胺能（DA）神经元实体和悬浮移植物在6-OHDA损伤免疫抑制大鼠脑实质内移植中的存活能力。当供体年龄在受孕后（PC）第34天至第56天之间时，悬浮移植物存活最好。移植物显示出许多健康的酪氨酸羟化酶免疫反应（TH-IR）神经元，这些神经元将广泛的神经炎过程发送到宿主纹状体。当供体年龄大于65天时，悬浮移植物成活率较差。当供体年龄在44至65天之间时，实体植入物显示出与TH-IR神经元相当的活力。当供体组织大于72天时，没有实体移植物含有TH-IR细胞。悬浮移植和实体移植的存活率与强健移植物相当，但实体移植物比悬浮移植物具有更大的移植物间变异性，特别是在更边缘的移植物中。我们的研究结果表明，人胚DA悬浮移植物的存活上限与人黑质纹状体通路的发育时期密切相关。与悬浮移植相比，实体人胚胎DA移植的供体年龄“窗口期”似乎延长了约9天。这些数据表明，移植人中脑DA神经元的年龄上限应为悬浮移植的PC天56，实体植入的PC天65。年龄较大的供者可能产生的移植物中存活的DA神经元较少。
In many species, graft survival and graft-derived behavioral recovery are affected by the embryonic donor age. We compared the ability of solid and suspension grafts of human embryonic mesencephalic dopaminergic (DA) neurons at different embryonic stages to survive intraparenchymal transplantation into 6-OHDA lesioned immunosuppressed rats. Suspension grafts survived best when donor age was between postconception (PC) days 34 and 56. Transplants displayed numerous healthy tyrosine hydroxylase immunoreactive (TH-IR) neurons which sent extensive neuritic processes into the host striatum. Suspension grafts survived poorly when donor age was greater than 65 days. Solid implants displayed comparable viability of TH-IR neurons when donor age was between 44 and 65 days. No solid grafts contained TH-IR cells when donor tissue was older than 72 days. The suspension and solid methods of transplantation resulted in comparable survival of robust grafts, but solid grafts resulted in more intergraft variability than suspension grafts, particularly among the more marginal implants. Our results demonstrate that the upper limit for survival of human embryonic DA suspension grafts correlates well with the period of development of the human nigrostriatal pathway. The ''window'' for donor age of solid human embryonic DA grafts appears to be extended by about 9 days in comparison to suspension grafts. These data suggest that the upper age limit for grafting human mesencephalic DA neurons should be PC day 56 for suspension grafts, and PC day 65 for solid implants. Older donors are likely to produce grafts with fewer surviving DA neurons.