Therapeutic potential of stem/progenitor cells in human skeletal muscle for cardiovascular regeneration

Tetsuya Nomura, Eishi Ashihara, Kento Tateishi, Tomomi Ueyama, Tomosaburo Takahashi, Masaaki Yamagishi, Toshikazu Kubo, Hitoshi Yaku, Hiroaki Matsubara, Hidemasa Oh

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Although myoblast transplantation in patients with ischemic heart failure results in a significant improvement of cardiac function, subsequent studies have consistently shown the myotubes formation in the absence of electromechanical coupling with the neighboring host myocardium, accompanied with the short-term release of paracrine effectors from implanted cells. One major pitfall of using myoblasts is that transplanted cells do not differentiate into cardiomyocytes, which may cause the inherent proarrhythmogenic events. Therefore, whether a discrete subpopulation in heterogeneous muscle-cell cultures is responsible for substantial cardiovascular regeneration has yet to be investigated. We describe here the isolation of progenitor cells from human skeletal muscle. These cells proliferated as non-adherent myospheres in suspension and displayed early embryonic factors and mesenchymal cell-like characteristics. Flow cytometric analyses demonstrated that CD56/N-CAM/Leu-19, a neural cell adhesion molecule abundantly present in myoblasts, was absent in myospheres but was expressed in an adherent cell population containing myogenic precursors. Myosphere-derived progenitor cells (MDPCs) differentiated in culture to produce cardiac, smooth muscle, and endothelial cells. Transplantation of MDPCs into ischemic hearts in NOD/scid mice promoted angiogenesis with substantial cardiovascular regeneration. Our results provide a foundation to further study the cell and biological function of human MDPCs which may have potential therapeutic implications.

Original languageEnglish
Pages (from-to)293-300
Number of pages8
JournalCurrent Stem Cell Research and Therapy
Volume2
Issue number4
DOIs
Publication statusPublished - Dec 2007
Externally publishedYes

Fingerprint

Regeneration
Skeletal Muscle
Stem Cells
Myoblasts
Cardiac Myocytes
Therapeutics
Transplantation
Neural Cell Adhesion Molecules
Inbred NOD Mouse
Skeletal Muscle Fibers
Muscle Cells
Smooth Muscle Myocytes
Suspensions
Myocardium
Endothelial Cells
Heart Failure
Cell Culture Techniques
Population

Keywords

  • Cardiac differentiation
  • Human skeletal muscle
  • Mesenchymal cells
  • Myocardial infarction
  • Stem cells
  • Transplantation

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Therapeutic potential of stem/progenitor cells in human skeletal muscle for cardiovascular regeneration. / Nomura, Tetsuya; Ashihara, Eishi; Tateishi, Kento; Ueyama, Tomomi; Takahashi, Tomosaburo; Yamagishi, Masaaki; Kubo, Toshikazu; Yaku, Hitoshi; Matsubara, Hiroaki; Oh, Hidemasa.

In: Current Stem Cell Research and Therapy, Vol. 2, No. 4, 12.2007, p. 293-300.

Research output: Contribution to journalArticle

Nomura, T, Ashihara, E, Tateishi, K, Ueyama, T, Takahashi, T, Yamagishi, M, Kubo, T, Yaku, H, Matsubara, H & Oh, H 2007, 'Therapeutic potential of stem/progenitor cells in human skeletal muscle for cardiovascular regeneration', Current Stem Cell Research and Therapy, vol. 2, no. 4, pp. 293-300. https://doi.org/10.2174/157488807782793808
Nomura, Tetsuya ; Ashihara, Eishi ; Tateishi, Kento ; Ueyama, Tomomi ; Takahashi, Tomosaburo ; Yamagishi, Masaaki ; Kubo, Toshikazu ; Yaku, Hitoshi ; Matsubara, Hiroaki ; Oh, Hidemasa. / Therapeutic potential of stem/progenitor cells in human skeletal muscle for cardiovascular regeneration. In: Current Stem Cell Research and Therapy. 2007 ; Vol. 2, No. 4. pp. 293-300.
@article{a7d77d368e924275898d54a8a6828149,
title = "Therapeutic potential of stem/progenitor cells in human skeletal muscle for cardiovascular regeneration",
abstract = "Although myoblast transplantation in patients with ischemic heart failure results in a significant improvement of cardiac function, subsequent studies have consistently shown the myotubes formation in the absence of electromechanical coupling with the neighboring host myocardium, accompanied with the short-term release of paracrine effectors from implanted cells. One major pitfall of using myoblasts is that transplanted cells do not differentiate into cardiomyocytes, which may cause the inherent proarrhythmogenic events. Therefore, whether a discrete subpopulation in heterogeneous muscle-cell cultures is responsible for substantial cardiovascular regeneration has yet to be investigated. We describe here the isolation of progenitor cells from human skeletal muscle. These cells proliferated as non-adherent myospheres in suspension and displayed early embryonic factors and mesenchymal cell-like characteristics. Flow cytometric analyses demonstrated that CD56/N-CAM/Leu-19, a neural cell adhesion molecule abundantly present in myoblasts, was absent in myospheres but was expressed in an adherent cell population containing myogenic precursors. Myosphere-derived progenitor cells (MDPCs) differentiated in culture to produce cardiac, smooth muscle, and endothelial cells. Transplantation of MDPCs into ischemic hearts in NOD/scid mice promoted angiogenesis with substantial cardiovascular regeneration. Our results provide a foundation to further study the cell and biological function of human MDPCs which may have potential therapeutic implications.",
keywords = "Cardiac differentiation, Human skeletal muscle, Mesenchymal cells, Myocardial infarction, Stem cells, Transplantation",
author = "Tetsuya Nomura and Eishi Ashihara and Kento Tateishi and Tomomi Ueyama and Tomosaburo Takahashi and Masaaki Yamagishi and Toshikazu Kubo and Hitoshi Yaku and Hiroaki Matsubara and Hidemasa Oh",
year = "2007",
month = "12",
doi = "10.2174/157488807782793808",
language = "English",
volume = "2",
pages = "293--300",
journal = "Current Stem Cell Research and Therapy",
issn = "1574-888X",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Therapeutic potential of stem/progenitor cells in human skeletal muscle for cardiovascular regeneration

AU - Nomura, Tetsuya

AU - Ashihara, Eishi

AU - Tateishi, Kento

AU - Ueyama, Tomomi

AU - Takahashi, Tomosaburo

AU - Yamagishi, Masaaki

AU - Kubo, Toshikazu

AU - Yaku, Hitoshi

AU - Matsubara, Hiroaki

AU - Oh, Hidemasa

PY - 2007/12

Y1 - 2007/12

N2 - Although myoblast transplantation in patients with ischemic heart failure results in a significant improvement of cardiac function, subsequent studies have consistently shown the myotubes formation in the absence of electromechanical coupling with the neighboring host myocardium, accompanied with the short-term release of paracrine effectors from implanted cells. One major pitfall of using myoblasts is that transplanted cells do not differentiate into cardiomyocytes, which may cause the inherent proarrhythmogenic events. Therefore, whether a discrete subpopulation in heterogeneous muscle-cell cultures is responsible for substantial cardiovascular regeneration has yet to be investigated. We describe here the isolation of progenitor cells from human skeletal muscle. These cells proliferated as non-adherent myospheres in suspension and displayed early embryonic factors and mesenchymal cell-like characteristics. Flow cytometric analyses demonstrated that CD56/N-CAM/Leu-19, a neural cell adhesion molecule abundantly present in myoblasts, was absent in myospheres but was expressed in an adherent cell population containing myogenic precursors. Myosphere-derived progenitor cells (MDPCs) differentiated in culture to produce cardiac, smooth muscle, and endothelial cells. Transplantation of MDPCs into ischemic hearts in NOD/scid mice promoted angiogenesis with substantial cardiovascular regeneration. Our results provide a foundation to further study the cell and biological function of human MDPCs which may have potential therapeutic implications.

AB - Although myoblast transplantation in patients with ischemic heart failure results in a significant improvement of cardiac function, subsequent studies have consistently shown the myotubes formation in the absence of electromechanical coupling with the neighboring host myocardium, accompanied with the short-term release of paracrine effectors from implanted cells. One major pitfall of using myoblasts is that transplanted cells do not differentiate into cardiomyocytes, which may cause the inherent proarrhythmogenic events. Therefore, whether a discrete subpopulation in heterogeneous muscle-cell cultures is responsible for substantial cardiovascular regeneration has yet to be investigated. We describe here the isolation of progenitor cells from human skeletal muscle. These cells proliferated as non-adherent myospheres in suspension and displayed early embryonic factors and mesenchymal cell-like characteristics. Flow cytometric analyses demonstrated that CD56/N-CAM/Leu-19, a neural cell adhesion molecule abundantly present in myoblasts, was absent in myospheres but was expressed in an adherent cell population containing myogenic precursors. Myosphere-derived progenitor cells (MDPCs) differentiated in culture to produce cardiac, smooth muscle, and endothelial cells. Transplantation of MDPCs into ischemic hearts in NOD/scid mice promoted angiogenesis with substantial cardiovascular regeneration. Our results provide a foundation to further study the cell and biological function of human MDPCs which may have potential therapeutic implications.

KW - Cardiac differentiation

KW - Human skeletal muscle

KW - Mesenchymal cells

KW - Myocardial infarction

KW - Stem cells

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=38349088907&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38349088907&partnerID=8YFLogxK

U2 - 10.2174/157488807782793808

DO - 10.2174/157488807782793808

M3 - Article

VL - 2

SP - 293

EP - 300

JO - Current Stem Cell Research and Therapy

JF - Current Stem Cell Research and Therapy

SN - 1574-888X

IS - 4

ER -