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Murine and human myogenic cells identified by elevated aldehyde dehydrogenase activity: Implications for muscle regeneration and repair

Vella, JB and Thompson, SD and Bucsek, MJ and Song, M and Huard, J (2011) Murine and human myogenic cells identified by elevated aldehyde dehydrogenase activity: Implications for muscle regeneration and repair. PLoS ONE, 6 (12).

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Abstract

Background: Despite the initial promise of myoblast transfer therapy to restore dystrophin in Duchenne muscular dystrophy patients, clinical efficacy has been limited, primarily by poor cell survival post-transplantation. Murine muscle derived stem cells (MDSCs) isolated from slowly adhering cells (SACs) via the preplate technique, induce greater muscle regeneration than murine myoblasts, primarily due to improved post-transplantation survival, which is conferred by their increased stress resistance capacity. Aldehyde dehydrogenase (ALDH) represents a family of enzymes with important morphogenic as well as oxidative damage mitigating roles and has been found to be a marker of stem cells in both normal and malignant tissue. In this study, we hypothesized that elevated ALDH levels could identify murine and human muscle derived cell (hMDC) progenitors, endowed with enhanced stress resistance and muscle regeneration capacity. Methodology/Principal Findings: Skeletal muscle progenitors were isolated from murine and human skeletal muscle by a modified preplate technique and unfractionated enzymatic digestion, respectively. ALDHhisubpopulations isolated by fluorescence activate cell sorting demonstrated increased proliferation and myogenic differentiation capacities compared to their ALDHlocounterparts when cultivated in oxidative and inflammatory stress media conditions. This behavior correlated with increased intracellular levels of reduced glutathione and superoxide dismutase. ALDHhimurine myoblasts were observed to exhibit an increased muscle regenerative potential compared to ALDHlomyoblasts, undergo multipotent differentiation (osteogenic and chondrogenic), and were found predominately in the SAC fraction, characteristics that are also observed in murine MDSCs. Likewise, human ALDHhihMDCs demonstrated superior muscle regenerative capacity compared to ALDHlohMDCs. Conclusions: The methodology of isolating myogenic cells on the basis of elevated ALDH activity yielded cells with increased stress resistance, a behavior that conferred increased regenerative capacity of dystrophic murine skeletal muscle. This result demonstrates the critical role of stress resistance in myogenic cell therapy as well as confirms the role of ALDH as a marker for rapid isolation of murine and human myogenic progenitors for cell therapy. © 2011 Vella et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Vella, JB
Thompson, SD
Bucsek, MJ
Song, M
Huard, J
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorRameshwar, PranelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 15 December 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0029226
Schools and Programs: Swanson School of Engineering > Bioengineering
Refereed: Yes
MeSH Headings: Adult; Aged; Aldehyde Dehydrogenase--metabolism; Animals; Antioxidants--metabolism; Cell Proliferation; Cell Separation; Chondrogenesis; Female; Flow Cytometry; Humans; Male; Mice; Mice, Inbred C57BL; Middle Aged; Muscle Cells--cytology; Muscle Cells--enzymology; Muscle, Skeletal--cytology; Muscle, Skeletal--physiology; Myoblasts--cytology; Osteogenesis; Regeneration--physiology; Stress, Physiological; Wound Healing--physiology
Other ID: NLM PMC3240661
PubMed Central ID: PMC3240661
PubMed ID: 22195027
Date Deposited: 07 Sep 2012 19:37
Last Modified: 20 Dec 2018 00:55
URI: http://d-scholarship.pitt.edu/id/eprint/14005

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