Zaman V, Turner D A, Shetty A K
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Cell Transplant. 2001 Jan-Feb;10(1):41-52.
Fetal hippocampal CA3 cell grafts exhibit dramatically enhanced survival when transplanted at an early postlesion delay of 4 days into the lesioned CA3 region of adult hippocampus. However, survival of these homotopic grafts following placement at late postlesion time points when the host milieu is considerably less receptive to grafts is unknown. We hypothesize that an extended postlesion delay at the time of grafting will lead to significant diminution in cell survival of both homotopic and heterotopic fetal transplants grafted to lesioned adult CNS. We quantitatively investigated absolute cell survival of 5'-bromodeoxyuridine-labeled fetal hippocampal CA3 and CA1 cell grafts, following transplantation into the lesioned CA3 region of adult rat hippocampus, at a delay of 45 days after a unilateral intracerebroventricular administration of kainic acid (KA). Survival of these grafts was also analyzed in intact CA3 of the hippocampus contralateral to KA administration for comparison. In lesioned CA3 region, CA3 (homotopic) and CA1 (heterotopic) grafts exhibited comparable but only moderate survival, with a recovery of only 21-31% of injected cells. Cell survival in these grafts into lesioned hippocampus was similar to survival of grafts placed into the contralateral intact CA3 region. These results are in sharp contrast to increased graft survival measured following transplants performed at 4 days postlesion. In such grafts placed early, there was both a significantly higher cell survival than grafts placed into the intact CA3 region and also a characteristic differential survival based on graft cell specificity to the lesioned CA3 region (Zaman et al., Exp. Neurol., 161:535-561, 2000). Thus, the enhanced conduciveness of lesioned CA3 region for survival of homotopic CA3 cell grafts observed at 4 days postlesion wanes by 45 days postlesion to that of intact CA3 region, in spite of residual loss of CA3 neurons with the lesion. Strategies that considerably augment graft cell survival may therefore be critical for optimal integration of fetal grafts into the adult CNS at late postlesion time points.
当在损伤后4天的早期延迟时间移植到成年海马体损伤的CA3区域时，胎儿海马体CA3细胞移植显示出显著提高的存活率。然而，当在损伤后较晚时间点植入这些同基因移植体时，其存活率尚不清楚，因为此时宿主环境对移植体的接受度大大降低。我们推测，移植时损伤后延迟时间延长将导致移植到成年中枢神经系统损伤部位的同基因和异基因胎儿移植细胞的存活率显著降低。我们定量研究了5'-溴脱氧尿苷标记的胎儿海马体CA3和CA1细胞移植体在单侧脑室内注射 kainic 酸（KA）45天后移植到成年大鼠海马体损伤的CA3区域后的绝对细胞存活率。还对KA注射对侧海马体完整CA3中的这些移植体存活率进行了分析，以作比较。在损伤的CA3区域，CA3（同基因）和CA1（异基因）移植体显示出相当但仅为中等的存活率，注入细胞的回收率仅为21%-31%。这些移植到损伤海马体中的移植体的细胞存活率与移植到对侧完整CA3区域的移植体存活率相似。这些结果与损伤后4天进行移植后测得的移植体存活率增加形成鲜明对比。在早期植入的此类移植体中，细胞存活率不仅显著高于植入完整CA3区域的移植体，而且还基于移植细胞对损伤CA3区域的特异性表现出特征性的差异存活率（Zaman等人，《实验神经病学》，161:535-561，2000）。因此，尽管损伤导致CA3神经元有残余损失，但损伤后4天观察到的损伤CA3区域对同基因CA3细胞移植体存活的增强促进作用在损伤后45天时减弱至与完整CA3区域相同的水平。因此，在损伤后较晚时间点，大幅提高移植细胞存活率的策略对于胎儿移植体最佳整合到成年中枢神经系统可能至关重要。
