Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease.
Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease.
复制标题
DOI：
10.1111/nmo.12635
复制
发表时间：
2015-10
影响因子：
3.5
通讯作者：
Belkind-Gerson J
中科院分区：
文献类型：
--
作者：
Cheng LS;Hotta R;Graham HK;Nagy N;Goldstein AM;Belkind-Gerson J
肠神经干细胞（ENSC）移植有望成为包括先天性巨结肠在内的肠神经病的潜在治疗方法。已经描述了通过剖腹手术递送可移植细胞，但是我们提出了一种新颖的、微创的内窥镜细胞递送方法。从出生后供体小鼠的离体肠道培养用于移植的ENSC。12只受体小鼠，包括患有远端结肠无神经节细胞症的Ednrb−/−小鼠，在直视下使用30号汉密尔顿针通过刚性膀胱输尿管镜进行ENSC结肠镜注射。在手术后1-4周研究细胞植入、存活和神经胶质细胞分化。所有受体小鼠均耐受该手术，无并发症，并存活至处死。在12只受体小鼠中的9只中，在结肠壁内发现移植细胞，并分化为肠神经元和神经胶质。ENSC的内窥镜注射是一种安全可靠的细胞递送方法，并且可以用于将大量细胞递送到疾病的特定区域。这种微创内窥镜方法可能对未来人类应用细胞治疗神经肠道疾病有益。
Transplantation of enteric neural stem cells (ENSC) holds promise as a potential therapy for enteric neuropathies, including Hirschsprung disease. Delivery of transplantable cells via laparotomy has been described, but we propose a novel, minimally-invasive endoscopic method of cell delivery. ENSC for transplantation were cultured from dissociated gut of postnatal donor mice. Twelve recipient mice, including Ednrb−/− mice with distal colonic aganglionosis, underwent colonoscopic injection of ENSC under direct vision using a 30-gauge Hamilton needle passed through a rigid cystoureteroscope. Cell engraftment, survival, and neuroglial differentiation were studied 1–4 weeks after the procedure. All recipient mice tolerated the procedure without complications and survived to sacrifice. Transplanted cells were found within the colonic wall in 9 of 12 recipient mice with differentiation into enteric neurons and glia. Endoscopic injection of ENSC is a safe and reliable method for cell delivery, and can be used to deliver a large number of cells to a specific area of disease. This minimally-invasive endoscopic approach may prove beneficial to future human applications of cell therapy for neurointestinal disease.