Russ Kaspar, Flores Joseph, Brudek Tomasz, Doudet Doris J
Pacific Parkinson's Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
The Research Laboratory for Stereology and Neuroscience, Bispebjerg University Hospital, Bispebjerg Bakke 23, Entrance 11B, 2.sal, 2400, Copenhagen NV, Denmark.
J Neural Transm (Vienna). 2017 Apr;124(4):455-462. doi: 10.1007/s00702-017-1683-1. Epub 2017 Feb 4.
Following the failure of a Phase II clinical study evaluating human retinal pigment epithelial (hRPE) cell implants as a potential treatment option for Parkinson's disease, speculation has centered on implant function and survival as possible contributors to the therapeutic outcomes. We recently reported that neonatal hRPE cells, similar to hRPE cells used in the Phase II clinical study, produced short-lived in vitro and limited in vivo trophic factors, which supports that assumption. We hypothesize that the switch from fetal to neonatal hRPE cells, between the Phase I and the Phase II clinical trial may be partly responsible for the later negative outcomes. To investigate this hypothesis, we used two neonatal hRPE cell lots, prepared in a similar manner to neonatal hRPE cells used in the Phase II clinical study, and compared them to previously evaluated fetal hRPE cells for behavioral changes following unilateral striatal implantation in 6-hydroxydopamine-lesioned rats. The results showed that only fetal, not neonatal, hRPE cell implants, were able to improve behavioral outcomes following striatal implantation in the lesioned rats. These data suggest that fetal hRPE cells may be preferential to neonatal hRPE cells in restoring behavioral deficits.
在一项评估人视网膜色素上皮（hRPE）细胞植入作为帕金森病潜在治疗选择的II期临床研究失败后，猜测主要集中在植入物的功能和存活情况，认为它们可能是导致治疗结果的因素。我们最近报道，与II期临床研究中使用的hRPE细胞相似，新生hRPE细胞在体外产生的营养因子寿命短暂，在体内产生的营养因子有限，这支持了上述假设。我们推测，在I期和II期临床试验之间从胎儿hRPE细胞转换为新生hRPE细胞可能是导致后期负面结果的部分原因。为了研究这一假设，我们使用了两批新生hRPE细胞，其制备方式与II期临床研究中使用的新生hRPE细胞相似，并将它们与之前评估过的胎儿hRPE细胞进行比较，观察6-羟基多巴胺损伤大鼠单侧纹状体植入后行为的变化。结果显示，在损伤大鼠的纹状体植入后，只有胎儿hRPE细胞植入物能够改善行为结果。这些数据表明，在恢复行为缺陷方面，胎儿hRPE细胞可能比新生hRPE细胞更具优势。
