Kawashima Akihiro, Yasuhara Rika, Akino Ryosuke, Mishima Kenji, Nasu Michiko, Sekizawa Akihiko
Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8666, Japan.
Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan.
Heliyon. 2020 Mar 4;6(3):e03409. doi: 10.1016/j.heliyon.2020.e03409. eCollection 2020 Mar.
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, PDGFRα, and Sca-1 via fluorescence-activated cell sorting. The PDGFRαSca-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 PDGFRαSca-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 PDGFRαSca-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.
产前分子检测的进展使在妊娠早期诊断大多数遗传疾病成为可能。子宫内间充质干细胞(MSC)疗法可能成为治愈不治之症的有力工具。考虑到这一点,这种方法可以改善潜在的身体和功能损伤。然而,怀孕期间母体T细胞在胎儿中迁移被认为是实现胎儿植入的主要障碍。我们研究了使用母体脂肪来源干细胞(ADSC)进行子宫内移植以提高植入率的可能性,从而降低移植排斥的风险。在此,通过在小鼠模型中进行子宫内干细胞移植,检测了使用同基因和母体ADSC移植物的胎儿脑植入情况。通过荧光激活细胞分选,使用间充质干细胞标志物血小板衍生生长因子受体α(PDGFRα)和干细胞抗原-1(Sca-1)纯化ADSC。在胚胎第14.5天,将PDGFRαSca-1 ADSC移植到胎儿脑室内(ICV)。用PDGFRαSca-1 ADSC进行子宫内移植后,移植的移植物至少生长28天,并且在移植物中也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,用母体PDGFRαSca-1 ADSC进行子宫内移植到胎儿ICV可能对先天性神经疾病的治疗有益,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。