EphA7+perivascular cells as myogenic and angiogenic precursors improving skeletal muscle regeneration in a muscular dystrophic mouse model. （EphA7陽性周細胞は、筋ジストロフィーマウスモデルにおいて、骨格筋再生能を改善する）
著者
鹿野, 耕平
(Kano, Kohei)
上位タイトル
Stem cell research
Vol.47,
(2020.
7)
,p.101914-
識別番号
ISSN
1873-5061
DOI
10.1016/j.scr.2020.101914
その他
PMID: 32738632
博士論文情報
学位授与番号
10107A549
学位授与年月日
2020-09-30
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
Skeletal muscle has a capacity for muscular regeneration mediated by satellite cells (SCs) and non-SCs. Although it is proposed that non-SCs are attractive therapeutic targets for dystrophies, the biological properties of these cells remain unclear. We have recently identified novel multipotent pericytes (PCs), capillary stem cells (CapSCs) derived from the microvasculature. In the present study, we determined if CapSCs contributed to myogenic regeneration using muscular dystrophy mouse model. CapSCs were isolated as EphA7+NG2+PCs from the subcutaneous adipose tissues of GFP-transgenic mice. Co-culture with C2C12 myoblast cells showed that CapSCs effectively enhanced myogenesis as compared to controls including EphA7- PCs and adipose stromal cells (ASCs). CapSCs transplanted in cardiotoxin-injured gastrocnemius muscles were well differentiated into both muscle fibers and microvessels, as compared to controls. At three weeks after cell-transplantation into the limbs of the mdx/utrn-/-mouse, CapSCs increased the number of GFP+myofibers along with dystrophin expression and the area size of myofibers, and also enhanced the muscular mass and its performance, assessed by treadmill test as compared to controls. In conclusion, CapSCs have potent myogenic regeneration capacity and improved the pathological condition in a muscular dystrophy mouse. Thus, CapSCs are an attractive cellular source in regenerative therapy for muscular dystrophy.
