Department of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Sci Rep. 2022 Apr 28;12(1):6990. doi: 10.1038/s41598-022-10077-3.
Hirschsprung's disease is a congenital entero-neuropathy that causes chronic constipation and intestinal obstruction. New treatments for entero-neuropathy are needed because current surgical strategies have limitations5. Entero-neuropathy results from enteric nervous system dysfunction due to incomplete colonization of the distal intestine by neural crest-derived cells. Impaired cooperation between the enteric nervous system and intestinal pacemaker cells may also contribute to entero-neuropathy. Stem cell therapy to repair these multiple defects represents a novel treatment approach. Dental pulp stem cells derived from deciduous teeth (dDPSCs) are multipotent cranial neural crest-derived cells, but it remains unknown whether dDPSCs have potential as a new therapy for entero-neuropathy. Here we show that intravenous transplantation of dDPSCs into the Japanese Fancy-1 mouse, an established model of hypoganglionosis and entero-neuropathy, improves large intestinal structure and function and prolongs survival. Intravenously injected dDPSCs migrate to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Transplanted dDPSCs differentiate into both pacemaker cells and enteric neurons in the proximal colon to improve electrical and peristaltic activity, in addition to their paracrine effects. Our findings indicate that transplanted dDPSCs can differentiate into different cell types to correct entero-neuropathy-associated defects.
先天性巨结肠是一种先天性肠神经病变，可导致慢性便秘和肠梗阻。由于目前的手术策略存在局限性，因此需要新的肠神经病变治疗方法。肠神经病变是由于神经嵴来源的细胞对远端肠道不完全定植导致肠神经系统功能障碍引起的。肠道神经系统和肠道起搏细胞之间合作受损也可能导致肠神经病变。修复这些多种缺陷的干细胞治疗代表了一种新的治疗方法。乳牙牙髓干细胞（dDPSCs）是多能颅神经嵴来源细胞，但尚不清楚 dDPSCs 是否有可能成为肠神经病变的新治疗方法。在这里，我们表明，将 dDPSCs 静脉内移植到日本 fancy-1 小鼠中，这是一种低神经节细胞症和肠神经病变的既定模型，可以改善大肠结构和功能并延长存活时间。静脉内注射的 dDPSCs 通过基质细胞衍生因子-1α 和 C-X-C 趋化因子受体 4 之间的相互作用迁移到受影响的肠道区域。移植的 dDPSCs 分化为近端结肠中的起搏细胞和肠神经元，除了旁分泌作用外，还可以改善电和蠕动活动。我们的研究结果表明，移植的 dDPSCs 可以分化为不同的细胞类型来纠正与肠神经病变相关的缺陷。
