Kihara Yuki, Tanaka Yukie, Ikeda Masanari, Homma Jun, Takagi Ryo, Ishigaki Keiko, Yamanouchi Keitaro, Honda Hiroaki, Nagata Satoru, Yamato Masayuki
Department of Pediatrics, Tokyo Women's Medical University, School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan.
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan.
Regen Ther. 2022 Oct 20;21:486-493. doi: 10.1016/j.reth.2022.10.003. eCollection 2022 Dec.
Duchenne muscular dystrophy (DMD) is a progressive disease that leads to damage of muscle and myocardium due to genetic abnormalities in the dystrophin gene. In utero cell transplantation that might facilitate allogenic transplantation is worth considering to treat this disease.
We performed allogeneic in utero transplantation of GFP-positive myoblasts and adipose-derived mesenchymal stem cells into murine DMD model animals. The transplantation route in this study was fetal intraperitoneal transplantation and transplacental transplantation. Transplanted animals were examined at 4-weeks old by immunofluorescence staining and RT-qPCR.
No GFP-positive cells were found by immunofluorescence staining of skeletal muscle and no GFP mRNA was detected by RT-qPCR in any animal, transplantation method and cell type. Compared with previous reports, myoblast transplantation exhibited an equivalent mortality rate, but adipose-derived stem cell (ASC) transplantation produced a higher mortality rate.
In utero transplantation of myoblasts or ASCs to murine models of DMD does not lead to engraftment and, in ASC transplantation primarily, frequently results in fetal death.
杜氏肌营养不良症（DMD）是一种进行性疾病，由于肌营养不良蛋白基因的遗传异常导致肌肉和心肌受损。子宫内细胞移植可能有助于同种异体移植，值得考虑用于治疗这种疾病。
我们将绿色荧光蛋白（GFP）阳性的成肌细胞和脂肪来源的间充质干细胞同种异体移植到小鼠DMD模型动物的子宫内。本研究中的移植途径是胎儿腹腔内移植和经胎盘移植。对移植后的动物在4周龄时进行免疫荧光染色和逆转录定量聚合酶链反应（RT-qPCR）检测。
在任何动物、移植方法和细胞类型中，通过骨骼肌的免疫荧光染色均未发现GFP阳性细胞，RT-qPCR也未检测到GFP mRNA。与先前的报道相比，成肌细胞移植的死亡率相当，但脂肪来源干细胞（ASC）移植的死亡率更高。
将成肌细胞或ASC子宫内移植到DMD小鼠模型中不会导致植入，主要是在ASC移植中，经常导致胎儿死亡。
