EphA7+ perivascular cells as myogenic and angiogenic precursors improving skeletal muscle regeneration in a muscular dystrophic mouse model

Kohei Kano; Kiwamu Horiuchi; Yuri Yoshida; Taiki Hayasaka; Maki Kabara; Yui Tomita; Takamitsu Tatsukawa; Risa Matsuo; Jun Sawada; Naoki Nakagawa; Naofumi Takehara; Naoyuki Hasebe; Jun-ichi Kawabe

Stem Cell Research (Aug 2020)

EphA7+ perivascular cells as myogenic and angiogenic precursors improving skeletal muscle regeneration in a muscular dystrophic mouse model

Kohei Kano,
Kiwamu Horiuchi,
Yuri Yoshida,
Taiki Hayasaka,
Maki Kabara,
Yui Tomita,
Takamitsu Tatsukawa,
Risa Matsuo,
Jun Sawada,
Naoki Nakagawa,
Naofumi Takehara,
Naoyuki Hasebe,
Jun-ichi Kawabe

Affiliations

Kohei Kano: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Kiwamu Horiuchi: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Yuri Yoshida: Department of Biochemistry, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Vascular Surgery, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Taiki Hayasaka: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Maki Kabara: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Yui Tomita: Department of Biochemistry, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Radiology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Takamitsu Tatsukawa: Department of Biochemistry, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Vascular Surgery, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Risa Matsuo: Department of Biochemistry, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Dermatology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Jun Sawada: Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Naoki Nakagawa: Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Naofumi Takehara: Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Naoyuki Hasebe: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan
Jun-ichi Kawabe: Department of Cardiovascular Regeneration and Innovation, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Department of Biochemistry, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan; Corresponding author at: Department of Biochemistry, Asahikawa Medical University, Asahikawa, 2-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan.

Journal volume & issue: Vol. 47
p. 101914

Abstract

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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.

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

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