Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice.
Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice.
复制标题
通过细胞移植补充胶原-VI改善Ullrich先天性肌营养不良模型小鼠的肌肉再生。
DOI：
10.1186/s13287-021-02514-3
复制
发表时间：
2021-08-09
影响因子：
7.5
通讯作者：
Sakurai H
中科院分区：
文献类型：
--
作者：
Takenaka-Ninagawa N;Kim J;Zhao M;Sato M;Jonouchi T;Goto M;Yoshioka CKB;Ikeda R;Harada A;Sato T;Ikeya M;Uezumi A;Nakatani M;Noguchi S;Sakurai H
间充质基质细胞（MSC）通过包括6型胶原（COL 6）在内的多种分泌因子作为骨骼肌稳态的支持细胞。COL 6A 1、COL 6A 2和COL 6A 3基因的几种突变导致Ullrich先天性肌营养不良症（UCMD）。骨骼肌再生缺陷已被报道为人类UCMD患者和UCMD模型小鼠的肌肉活检样品中的特征表型。然而，很少有人知道COL 6依赖性机制的发生和发展的缺陷。本研究旨在通过细胞移植补充COL 6以阐明UCMD的病理机制。为了测试COL 6补充是否对UCMD具有治疗效果，使用四种类型的MSC进行体内和体外实验：健康供体来源的原代MSC（pMSC）、来源于健康供体诱导的多能干细胞（iMSC）的MSC、COL 6敲除的iMSC（COL 6 KO-iMSC）和UCMD患者来源的iMSC（UCMD-iMSC）。当移植到免疫缺陷的UCMD模型（Col 6a 1 KO）小鼠的胫骨前肌中时，所有四种MSC类型都可以植入至少12周。如果MSC不是COL 6缺陷型（1型和2型），则通过MSC移植恢复COL 6蛋白。此外，在Col 6a 1 KO小鼠的肌肉再生和成熟的促进与移植的COL 6产生的MSC仅在补充有COL 6的区域。来自UCMD模型小鼠的骨骼肌卫星细胞（Col 6a 1 KO-MuSC）与1型或2型MSC共培养显示出改善的增殖、分化和成熟，而与3型或4型MSC共培养的那些则没有。这些发现表明，补充COL 6改善了UCMD模型小鼠的肌肉再生和成熟。在线版本包含补充材料，可通过10.1186/s13287-021-02514-3获得。
Mesenchymal stromal cells (MSCs) function as supportive cells on skeletal muscle homeostasis through several secretory factors including type 6 collagen (COL6). Several mutations of COL6A1, 2, and 3 genes cause Ullrich congenital muscular dystrophy (UCMD). Skeletal muscle regeneration deficiency has been reported as a characteristic phenotype in muscle biopsy samples of human UCMD patients and UCMD model mice. However, little is known about the COL6-dependent mechanism for the occurrence and progression of the deficiency. The purpose of this study was to clarify the pathological mechanism of UCMD by supplementing COL6 through cell transplantation. To test whether COL6 supplementation has a therapeutic effect for UCMD, in vivo and in vitro experiments were conducted using four types of MSCs: healthy donors derived-primary MSCs (pMSCs), MSCs derived from healthy donor induced pluripotent stem cell (iMSCs), COL6-knockout iMSCs (COL6KO-iMSCs), and UCMD patient-derived iMSCs (UCMD-iMSCs). All four MSC types could engraft for at least 12 weeks when transplanted into the tibialis anterior muscles of immunodeficient UCMD model (Col6a1KO) mice. COL6 protein was restored by the MSC transplantation if the MSCs were not COL6-deficient (types 1 and 2). Moreover, muscle regeneration and maturation in Col6a1KO mice were promoted with the transplantation of the COL6-producing MSCs only in the region supplemented with COL6. Skeletal muscle satellite cells derived from UCMD model mice (Col6a1KO-MuSCs) co-cultured with type 1 or 2 MSCs showed improved proliferation, differentiation, and maturation, whereas those co-cultured with type 3 or 4 MSCs did not. These findings indicate that COL6 supplementation improves muscle regeneration and maturation in UCMD model mice. The online version contains supplementary material available at 10.1186/s13287-021-02514-3.
登录
查看更多内容
影响因子：
3.7
作者：
Fukuta M;Nakai Y;Kirino K;Nakagawa M;Sekiguchi K;Nagata S;Matsumoto Y;Yamamoto T;Umeda K;Heike T;Okumura N;Koizumi N;Sato T;Nakahata T;Saito M;Otsuka T;Kinoshita S;Ueno M;Ikeya M;Toguchida J
通讯作者：
Toguchida J
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
影响因子：
30.8
作者：
Irwin, WA;Bergamin, N;Bonaldo, P
通讯作者：
Bonaldo, P
影响因子：
3.7
作者：
Minamitani, T;Ikuta, T;Matsumoto, K
通讯作者：
Matsumoto, K
影响因子：
--
作者：
Loeser, RF
通讯作者：
Loeser, RF