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Synchronized reconstitution of muscle fibers, peripheral nerves and blood vessels by murine skeletal muscle-derived CD34−/45− cells

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Abstract

In order to establish the practical isolation and usage of skeletal muscle-derived stem cells (MDSCs), we determined reconstitution capacity of CD34−/CD45− (Sk-DN) cells as a candidate somatic stem cell source for transplantation. Sk-DN cells were enzymatically isolated from GFP transgenic mice (C57/BL6N) skeletal muscle and sorted using fluorescence activated cell sorting (FACS), and expanded by collagen gel-based cell culture with bFGF and EGF. The number of Sk-DN cells was small after sorting (2–8 × 104); however, the number increased 10–20 fold (2–16 × 105) after 6 days of expansion culture, and the cells maintained immature state and multipotency, expressing mRNAs for mesodermal and ectodermal cell lineages. Transplantation of expanded Sk-DN cells into the severe muscle damage model (C57/BL6N wild-type) resulted in the synchronized reconstitution of blood vessels, peripheral nerves and muscle fibers following significant recovery of total muscle mass (57%) and contractile function (55%), whereas the non-cell-transplanted control group showed around 20% recovery in both factors. These reconstitution capacities were supported by the intrinsic plasticity of Sk-DN cells that can differentiate into muscular (skeletal muscle), vascular (pericyte, endothelial cell and smooth muscle) and peripheral nerve (Schwann cells and perineurium) cell lineages that was revealed by transplantation to non-muscle tissue (beneath renal capsule) and fluorescence in situ hybridization (FISH) analysis.

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, New Energy and Industrial Technology Development Organization, and Tokai University Research aid.

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Authors and Affiliations

  1. Muscle Physiology and Cell Biology Unit, Tokai University School of Medicine, Shimokasuya-143, Isehara, Kanagawa, 259-1143, Japan

    Tetsuro Tamaki, Yoshinori Okada, Yoshiyasu Uchiyama, Kayoko Tono, Maki Masuda, Akio Hoshi & Akira Akatsuka

  2. Department of Regenerative Medicine, Division of Basic Clinical Science, Tokai University School of Medicine, Shimokasuya-143, Isehara, Kanagawa, 259-1143, Japan

    Tetsuro Tamaki, Kayoko Tono & Mika Wada

  3. Teaching and Research Support Center, Tokai University School of Medicine, Kanagawa, 259-1143, Japan

    Yoshinori Okada & Akira Akatsuka

  4. Department of Orthopedics, Division of Surgery, Tokai University School of Medicine, Kanagawa, 259-1143, Japan

    Yoshiyasu Uchiyama

  5. Department of Urology, Division of Surgery, Tokai University School of Medicine, Kanagawa, 259-1143, Japan

    Akio Hoshi

Authors
  1. Tetsuro Tamaki
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  2. Yoshinori Okada
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  3. Yoshiyasu Uchiyama
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  4. Kayoko Tono
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  5. Maki Masuda
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  6. Mika Wada
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  7. Akio Hoshi
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  8. Akira Akatsuka
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Correspondence to Tetsuro Tamaki.

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Tamaki, T., Okada, Y., Uchiyama, Y. et al. Synchronized reconstitution of muscle fibers, peripheral nerves and blood vessels by murine skeletal muscle-derived CD34−/45− cells. Histochem Cell Biol 128, 349–360 (2007). https://doi.org/10.1007/s00418-007-0331-5

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  • DOI: https://doi.org/10.1007/s00418-007-0331-5

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