Skuk Daniel, Tremblay Jacques P
Axe Neurosciences, Research Center of the CHU de Quebec - CHUL, Québec, QC G1V 4G2, Canada.
Mol Ther Methods Clin Dev. 2017 May 12;5:232-240. doi: 10.1016/j.omtm.2017.05.002. eCollection 2017 Jun 16.
Cell therapy could be useful for the treatment of myopathies. A problem observed in mice, with different results and interpretations, is a significant death among the transplanted cells. We analyzed this problem in non-human primates, the animal model more similar to humans. Autologous or allogeneic myoblasts (with or without a reporter gene) were proliferated in vitro, labeled with [C]thymidine, and intramuscularly injected in macaques. Some monkeys were immunosuppressed for long-term follow-up. Cell-grafted regions were biopsied at different intervals and analyzed by radiolabel quantification and histology. Most radiolabel was lost during the first week after injection, regardless of whether the cells were allogeneic or autologous, the culture conditions, and the use or not of immunosuppression. There was no significant difference between 1 hr and 1 day post-transplantation, a significant decrease between days 1 and 3 (45% to 83%), a significant decrease between days 3 and 7 (80% to 92%), and no significant differences between 7 days and 3 weeks. Our results confirmed in non-human primates a progressive and significant death of the grafted myoblasts during the first week after administration, relatively similar to some observations in mice but with different kinetics.
细胞疗法可能对治疗肌病有用。在小鼠中观察到一个问题，其结果和解释各不相同，即移植细胞中有大量死亡现象。我们在与人类更为相似的动物模型——非人灵长类动物中分析了这个问题。将自体或异体成肌细胞（有或没有报告基因）在体外增殖，用[C]胸苷标记，然后肌肉注射到猕猴体内。一些猴子接受免疫抑制以进行长期随访。在不同时间间隔对细胞移植区域进行活检，并通过放射性标记定量和组织学分析。无论细胞是异体的还是自体的、培养条件如何以及是否使用免疫抑制，大多数放射性标记在注射后的第一周内就消失了。移植后1小时和1天之间没有显著差异，第1天和第3天之间显著下降（45%至83%），第3天和第7天之间显著下降（80%至92%），第7天和3周之间没有显著差异。我们在非人灵长类动物中的结果证实，给药后的第一周内移植的成肌细胞会逐渐且显著地死亡，这与在小鼠中的一些观察结果相对相似，但动力学有所不同。
