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Human muscle precursor cells overexpressing PGC-1α enhance early skeletal muscle tissue formation


Haralampieva, Deana; Salemi, Souzan; Dinulovic, Ivana; Sulser, Tullio; M Ametamey, Simon; Handschin, Christoph; Eberli, Daniel (2017). Human muscle precursor cells overexpressing PGC-1α enhance early skeletal muscle tissue formation. Cell Transplantation, 26(6):1103-1114.

Abstract

Muscle precursor cells (MPCs) are activated satellite cells capable of muscle fiber reconstruction. Therefore, autologous MPC transplantation is envisioned for the treatment of muscle diseases. However, the density of MPCs, as well as their proliferation and differentiation potential gradually decline with age. The goal of this research was to genetically modify human MPCs (hMPCs) to overexpress the peroxisome proliferator-activated receptor gamma coactivator (PGC-1α), a key regulator of exercise-mediated adaptation, and thereby to enhance early skeletal muscle formation and quality. We were able to confirm the sustained myogenic phenotype of the genetically modified hMPCs. While maintaining their viability and proliferation potential, PGC-1α modified hMPCs showed an enhanced myofiber formation capacity in vitro. Engineered muscle tissues were harvested 1, 2 and 4 weeks after subcutaneous injection of cell-collagen suspensions and histological analysis confirmed the earlier myotube formation in PGC-1α modified samples, predominantly of slow twitch myofibers. Increased contractile protein levels were detected by Western Blot. In summary, by genetically modifying hMPCs to overexpress PGC-1α we were able to promote early muscle fiber formation in vitro and in vivo, with an initial switch to slow type myofibers. Therefore, overexpressing PGC-1α is novel strategy to further enhance skeletal muscle tissue engineering.

Abstract

Muscle precursor cells (MPCs) are activated satellite cells capable of muscle fiber reconstruction. Therefore, autologous MPC transplantation is envisioned for the treatment of muscle diseases. However, the density of MPCs, as well as their proliferation and differentiation potential gradually decline with age. The goal of this research was to genetically modify human MPCs (hMPCs) to overexpress the peroxisome proliferator-activated receptor gamma coactivator (PGC-1α), a key regulator of exercise-mediated adaptation, and thereby to enhance early skeletal muscle formation and quality. We were able to confirm the sustained myogenic phenotype of the genetically modified hMPCs. While maintaining their viability and proliferation potential, PGC-1α modified hMPCs showed an enhanced myofiber formation capacity in vitro. Engineered muscle tissues were harvested 1, 2 and 4 weeks after subcutaneous injection of cell-collagen suspensions and histological analysis confirmed the earlier myotube formation in PGC-1α modified samples, predominantly of slow twitch myofibers. Increased contractile protein levels were detected by Western Blot. In summary, by genetically modifying hMPCs to overexpress PGC-1α we were able to promote early muscle fiber formation in vitro and in vivo, with an initial switch to slow type myofibers. Therefore, overexpressing PGC-1α is novel strategy to further enhance skeletal muscle tissue engineering.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Urological Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:3 February 2017
Deposited On:17 Feb 2017 11:11
Last Modified:05 Aug 2017 23:26
Publisher:Cognizant Communication Corporation
ISSN:0963-6897
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3727/096368917X694868
PubMed ID:28155812

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