Engraftment potential of maternal adipose-derived stem cells for fetal transplantation
Engraftment potential of maternal adipose-derived stem cells for fetal transplantation
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DOI：
10.1016/j.heliyon.2020.e03409
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发表时间：
2020-03-01
期刊：
影响因子：
4
通讯作者：
Sekizawa, Akihiko
中科院分区：
文献类型：
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作者：
Kawashima, Akihiro;Yasuhara, Rika;Sekizawa, Akihiko
产前分子检测的进步使得在妊娠早期诊断大多数遗传性疾病成为可能。子宫内间充质干细胞（MSC）疗法可以成为治愈不治之症的有力工具。考虑到这一点，这种方法可以减轻潜在的身体和功能损伤。然而，怀孕期间胎儿体内母体 T 细胞贩运的存在被认为是实现植入胎儿的主要障碍。我们研究了使用母体脂肪干细胞（ADSC）进行子宫内移植以改善植入的可能性，从而降低移植物排斥的风险。在此，通过子宫内干细胞移植在小鼠模型中检查使用同源和母体 ADSC 移植物的胎儿脑移植。使用间充质干细胞标记物 PDGFR α 和 Sca-1 通过荧光激活细胞分选纯化 ADSC。在E14.5时将PDGFR α(+)Sca-1(+) ADSC移植到胎儿脑室内(ICV)。子宫内移植PDGFR α(+)Sca-1(+) ADSC后移植物生长至少28天，并且移植物中还检测到成熟的神经元标志物。此外，使用母体分选的 ADSC 抑制了先天免疫反应，防止 CD8 T 细胞浸润到移植物中。因此，在子宫内将母体 PDGFR α(+)Sca-1(+) ADSC 移植到胎儿 ICV 中可能有益于治疗先天性神经系统疾病，因为它能够减少子宫内干细胞移植后的反应并分化为神经元谱系。
Advances in prenatal molecular testing have made it possible to diagnose most genetic disorders early in gestation. In utero mesenchymal stem cell (MSC) therapy can be a powerful tool to cure the incurable. With this in mind, this method could ameliorate potential physical and functional damage. However, the presence of maternal T cells trafficking in the fetus during pregnancy is thought to be the major barrier to achieving the engraftment into the fetus. We investigated the possibility of using maternal adipose-derived stem cells (ADSCs) for in utero transplantation to improve engraftment, thus lowering the risk of graft rejection. Herein, fetal brain engraftment using congenic and maternal ADSC grafts was examined via in utero stem cell transplantation in a mouse model. ADSCs were purified using the mesenchymal stem cell markers, PDGFR alpha, and Sca-1 via fluorescence-activated cell sorting. The PDGFR alpha(+)Sca-1(+) ADSCs were transplanted into the fetal intracerebroventricular (ICV) at E14.5. The transplanted grafts grew for at least 28 days after in utero transplantation with PDGFR alpha(+)Sca-1(+) ADSC, and mature neuronal markers were also detected in the grafts. Furthermore, using the maternal sorted ADSCs suppressed the innate immune response, preventing the infiltration of CD8 T cells into the graft. Thus, in utero transplantation into the fetal ICV with the maternal PDGFR alpha(+)Sca-1(+) ADSCs may be beneficial for the treatment of congenital neurological diseases because of the ability to reduce the responses after in utero stem cell transplantation and differentiate into neuronal lineages.