Dental pulp stem cells as a therapy for congenital entero-neuropathy.
Dental pulp stem cells as a therapy for congenital entero-neuropathy.
复制标题
DOI：
10.1038/s41598-022-10077-3
复制
发表时间：
2022-04-28
影响因子：
4.6
通讯作者：
Taguchi, Tomoaki
中科院分区：
文献类型：
--
作者：
Yoshimaru, Koichiro;Yamaza, Takayoshi;Kajioka, Shunichi;Sonoda, Soichiro;Yanagi, Yusuke;Matsuura, Toshiharu;Yoshizumi, Junko;Oda, Yoshinao;Iwata, Naoko;Takai, Chiho;Nakayama, Shinsuke;Taguchi, Tomoaki
先天性巨结肠症是一种先天性肠神经病变，会导致慢性便秘和肠梗阻。由于目前的手术治疗策略存在局限性，因此需要针对肠神经病变的新疗法 5 。肠神经病变源于肠神经系统功能障碍，这是由于神经嵴衍生细胞对远端肠道的定植不完全所致。肠神经系统与肠道起搏细胞之间的协作受损也可能导致肠神经病变。通过干细胞疗法修复这些多种缺陷代表了一种全新的治疗方法。源自乳牙的牙髓干细胞（dDPSCs）是多能的颅神经嵴衍生细胞，但dDPSCs是否具有作为肠神经病变新疗法的潜力仍不明确。在此，我们发现将dDPSCs静脉移植到日本观赏1号小鼠（一种已建立的神经节细胞减少症和肠神经病变模型）体内，可改善大肠的结构和功能并延长生存期。静脉注射的dDPSCs通过基质细胞衍生因子 - 1α与C - X - C趋化因子受体4型之间的相互作用迁移至肠道的受累区域。除了旁分泌作用外，移植的dDPSCs在近端结肠分化为起搏细胞和肠神经元，从而改善电活动和蠕动活动。我们的研究结果表明，移植的dDPSCs可分化为不同细胞类型，以纠正与肠神经病变相关的缺陷。
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.
登录
查看更多内容
影响因子：
5.9
作者：
Mabuchi, Yo;Morikawa, Satoru;Harada, Seiko;Niibe, Kunimichi;Suzuki, Sadafumi;Renault-Mihara, Francois;Houlihan, Diarmaid D.;Akazawa, Chihiro;Okano, Hideyuki;Matsuzaki, Yumi
通讯作者：
Matsuzaki, Yumi
影响因子：
3.7
作者：
Taniguchi M;Kajioka S;Shozib HB;Sawamura K;Nakayama S
通讯作者：
Nakayama S
DOI：
10.1073/pnas.1908756116
发表时间：
2019-12-26
影响因子：
11.1
作者：
Chatterjee, Sumantra;Nandakumar, Priyanka;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda
DOI：
10.1097/mpg.0b013e31812e65e0
发表时间：
2007-12-01
影响因子：
2.9
作者：
Burns, Alan J.
通讯作者：
Burns, Alan J.
影响因子：
3.7
作者：
Ma L;Makino Y;Yamaza H;Akiyama K;Hoshino Y;Song G;Kukita T;Nonaka K;Shi S;Yamaza T
通讯作者：
Yamaza T