Department of Pediatric Surgery, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan.
Department of Pediatrics, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan.
Pediatr Surg Int. 2022 Dec;38(12):1793-1798. doi: 10.1007/s00383-022-05224-w. Epub 2022 Sep 13.
Cell-based therapy is a potential treatment option for neurointestinal diseases by serving as a source of neural progenitor cells to replace missing or abnormal enteric neurons. Using an ex vivo transplantation model, we recently demonstrated that treatment with collagenase and fibronectin promotes infiltration of transplanted enteric neural crest cells (ENCCs) toward the colon lumen. The aim of this study was to determine whether this new method also promotes colonization of transplanted ENCCs in vivo.
Collagenase was applied locally on the anti-mesenteric area of the recipient colon using filter paper, followed by fibronectin. Neurospheres were generated from ENCCs isolated from fetal mouse intestines and transplanted into the collagenase and fibronectin-treated colon. Engraftment of neurospheres was confirmed by immunofluorescence.
Neurospheres transplanted onto PBS- or fibronectin-treated colons were not observed to infiltrate to the muscle layer. However, when used in combination with type I collagenase and fibronectin in the recipient colon, transplanted neurospheres reached Auerbach's plexus.
We demonstrated that transplanted neurospheres grow into Auerbach's plexus in the recipient colon pretreated with collagenase and fibronectin.
通过作为神经前体细胞的来源来替代缺失或异常的肠神经元,细胞疗法是治疗神经肠道疾病的一种潜在治疗选择。我们最近使用体外移植模型证明,用胶原酶和纤维连接蛋白处理可促进移植的肠神经嵴细胞(ENCC)向结肠腔渗透。本研究的目的是确定这种新方法是否也能促进移植的 ENCC 在体内定植。
将胶原酶用滤纸局部应用于受体结肠的对系膜区,然后应用纤维连接蛋白。从胎鼠肠道分离的 ENCC 生成神经球,并移植到胶原酶和纤维连接蛋白处理的结肠中。通过免疫荧光确认神经球的植入。
未观察到移植到 PBS 或纤维连接蛋白处理的结肠上的神经球渗透到肌肉层。然而,当与胶原酶和纤维连接蛋白联合用于受体结肠预处理时,移植的神经球到达了 Auerbach 丛。
我们证明,在胶原酶和纤维连接蛋白预处理的受体结肠中,移植的神经球生长为 Auerbach 丛。