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Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis.
Exp Cell Res. 2011 Apr 01; 317(6):873-85.EC

Abstract

The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a population of activated satellite cells even in aging. These data suggested the hypothesis that there is a population of myogenic precursor cells (mpcs) in EOM that is different from those in limb, with either elevated numbers of stem cells and/or mpcs with superior proliferative capacity compared to mpcs in limb. Using flow cytometry, EOM and limb muscle mononuclear cells were compared, and a number of differences were seen. Using two different cell isolation methods, EOM have significantly more mpcs per mg muscle than limb skeletal muscle. One specific subpopulation significantly increased in EOM compared to limb was positive for CD34 and negative for Sca-1, M-cadherin, CD31, and CD45. We named these the EOMCD34 cells. Similar percentages of EOMCD34 cells were present in both newborn EOM and limb muscle. They were retained in aged EOM, whereas the population decreased significantly in adult limb muscle and were extremely scarce in aged limb muscle. Most importantly, the percentage of EOMCD34 cells was elevated in the EOM from both the mdx and the mdx/utrophin(-/-) (DKO) mouse models of DMD and extremely scarce in the limb muscles of these mice. In vitro, the EOMCD34 cells had myogenic potential, forming myotubes in differentiation media. After determining a media better able to induce proliferation in these cells, a fusion index was calculated. The cells isolated from EOM had a 40% higher fusion index compared to the same cells isolated from limb muscle. The EOMCD34 cells were resistant to both oxidative stress and mechanical injury. These data support our hypothesis that the EOM may be spared in aging and in muscular dystrophies due to a subpopulation of mpcs, the EOMCD34 cells, that are retained in significantly higher percentages in normal, mdx and DKO mice EOM, appear to be resistant to elevated levels of oxidative stress and toxins, and actively proliferate throughout life. Current studies are focused on further defining the EOMCD34 cell subtype molecularly, with the hopes that this may shed light on a cell type with potential therapeutic use in patients with sarcopenia, cachexia, or muscular dystrophy.

Authors+Show Affiliations

Departments of Ophthalmology and Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21277300

Citation

Kallestad, Kristen M., et al. "Sparing of Extraocular Muscle in Aging and Muscular Dystrophies: a Myogenic Precursor Cell Hypothesis." Experimental Cell Research, vol. 317, no. 6, 2011, pp. 873-85.
Kallestad KM, Hebert SL, McDonald AA, et al. Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis. Exp Cell Res. 2011;317(6):873-85.
Kallestad, K. M., Hebert, S. L., McDonald, A. A., Daniel, M. L., Cu, S. R., & McLoon, L. K. (2011). Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis. Experimental Cell Research, 317(6), 873-85. https://doi.org/10.1016/j.yexcr.2011.01.018
Kallestad KM, et al. Sparing of Extraocular Muscle in Aging and Muscular Dystrophies: a Myogenic Precursor Cell Hypothesis. Exp Cell Res. 2011 Apr 1;317(6):873-85. PubMed PMID: 21277300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis. AU - Kallestad,Kristen M, AU - Hebert,Sadie L, AU - McDonald,Abby A, AU - Daniel,Mark L, AU - Cu,Sharon R, AU - McLoon,Linda K, Y1 - 2011/01/27/ PY - 2010/08/03/received PY - 2011/01/13/revised PY - 2011/01/15/accepted PY - 2011/2/1/entrez PY - 2011/2/1/pubmed PY - 2011/5/26/medline SP - 873 EP - 85 JF - Experimental cell research JO - Exp Cell Res VL - 317 IS - 6 N2 - The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a population of activated satellite cells even in aging. These data suggested the hypothesis that there is a population of myogenic precursor cells (mpcs) in EOM that is different from those in limb, with either elevated numbers of stem cells and/or mpcs with superior proliferative capacity compared to mpcs in limb. Using flow cytometry, EOM and limb muscle mononuclear cells were compared, and a number of differences were seen. Using two different cell isolation methods, EOM have significantly more mpcs per mg muscle than limb skeletal muscle. One specific subpopulation significantly increased in EOM compared to limb was positive for CD34 and negative for Sca-1, M-cadherin, CD31, and CD45. We named these the EOMCD34 cells. Similar percentages of EOMCD34 cells were present in both newborn EOM and limb muscle. They were retained in aged EOM, whereas the population decreased significantly in adult limb muscle and were extremely scarce in aged limb muscle. Most importantly, the percentage of EOMCD34 cells was elevated in the EOM from both the mdx and the mdx/utrophin(-/-) (DKO) mouse models of DMD and extremely scarce in the limb muscles of these mice. In vitro, the EOMCD34 cells had myogenic potential, forming myotubes in differentiation media. After determining a media better able to induce proliferation in these cells, a fusion index was calculated. The cells isolated from EOM had a 40% higher fusion index compared to the same cells isolated from limb muscle. The EOMCD34 cells were resistant to both oxidative stress and mechanical injury. These data support our hypothesis that the EOM may be spared in aging and in muscular dystrophies due to a subpopulation of mpcs, the EOMCD34 cells, that are retained in significantly higher percentages in normal, mdx and DKO mice EOM, appear to be resistant to elevated levels of oxidative stress and toxins, and actively proliferate throughout life. Current studies are focused on further defining the EOMCD34 cell subtype molecularly, with the hopes that this may shed light on a cell type with potential therapeutic use in patients with sarcopenia, cachexia, or muscular dystrophy. SN - 1090-2422 UR - https://www.unboundmedicine.com/medline/citation/21277300/Sparing_of_extraocular_muscle_in_aging_and_muscular_dystrophies:_a_myogenic_precursor_cell_hypothesis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(11)00031-0 DB - PRIME DP - Unbound Medicine ER -