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Injection of vessel-derived stem cells prevents dilated cardiomyopathy and promotes angiogenesis and endogenous cardiac stem cell proliferation in mdx/utrn-/- but not aged mdx mouse models for duchenne muscular dystrophy.
Stem Cells Transl Med. 2013 Jan; 2(1):68-80.SC

Abstract

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy. DMD patients lack dystrophin protein and develop skeletal muscle pathology and dilated cardiomyopathy (DCM). Approximately 20% succumb to cardiac involvement. We hypothesized that mesoangioblast stem cells (aorta-derived mesoangioblasts [ADMs]) would restore dystrophin and alleviate or prevent DCM in animal models of DMD. ADMs can be induced to express cardiac markers, including Nkx2.5, cardiac tropomyosin, cardiac troponin I, and α-actinin, and adopt cardiomyocyte morphology. Transplantation of ADMs into the heart of mdx/utrn(-/-) mice prior to development of DCM prevented onset of cardiomyopathy, as measured by echocardiography, and resulted in significantly higher CD31 expression, consistent with new vessel formation. Dystrophin-positive cardiomyocytes and increased proliferation of endogenous Nestin(+) cardiac stem cells were detected in ADM-injected heart. Nestin(+) striated cells were also detected in four of five mdx/utrn(-/-) hearts injected with ADMs. In contrast, when ADMs were injected into the heart of aged mdx mice with advanced fibrosis, no functional improvement was detected by echocardiography. Instead, ADMs exacerbated some features of DCM. No dystrophin protein, increase in CD31 expression, or increase in Nestin(+) cell proliferation was detected following ADM injection in aged mdx heart. Dystrophin was observed following transplantation of ADMs into the hearts of young mdx mice, however, suggesting that pathology in aged mdx heart may alter the fate of donor stem cells. In summary, ADMs delay or prevent development of DCM in dystrophin-deficient heart, but timing of stem cell transplantation may be critical for achieving benefit with cell therapy in DMD cardiac muscle.

Authors+Show Affiliations

Department of Animal Sciences, University of Illinois, Urbana, IL, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23283493

Citation

Chun, Ju Lan, et al. "Injection of Vessel-derived Stem Cells Prevents Dilated Cardiomyopathy and Promotes Angiogenesis and Endogenous Cardiac Stem Cell Proliferation in Mdx/utrn-/- but Not Aged Mdx Mouse Models for Duchenne Muscular Dystrophy." Stem Cells Translational Medicine, vol. 2, no. 1, 2013, pp. 68-80.
Chun JL, O'Brien R, Song MH, et al. Injection of vessel-derived stem cells prevents dilated cardiomyopathy and promotes angiogenesis and endogenous cardiac stem cell proliferation in mdx/utrn-/- but not aged mdx mouse models for duchenne muscular dystrophy. Stem Cells Transl Med. 2013;2(1):68-80.
Chun, J. L., O'Brien, R., Song, M. H., Wondrasch, B. F., & Berry, S. E. (2013). Injection of vessel-derived stem cells prevents dilated cardiomyopathy and promotes angiogenesis and endogenous cardiac stem cell proliferation in mdx/utrn-/- but not aged mdx mouse models for duchenne muscular dystrophy. Stem Cells Translational Medicine, 2(1), 68-80. https://doi.org/10.5966/sctm.2012-0107
Chun JL, et al. Injection of Vessel-derived Stem Cells Prevents Dilated Cardiomyopathy and Promotes Angiogenesis and Endogenous Cardiac Stem Cell Proliferation in Mdx/utrn-/- but Not Aged Mdx Mouse Models for Duchenne Muscular Dystrophy. Stem Cells Transl Med. 2013;2(1):68-80. PubMed PMID: 23283493.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Injection of vessel-derived stem cells prevents dilated cardiomyopathy and promotes angiogenesis and endogenous cardiac stem cell proliferation in mdx/utrn-/- but not aged mdx mouse models for duchenne muscular dystrophy. AU - Chun,Ju Lan, AU - O'Brien,Robert, AU - Song,Min Ho, AU - Wondrasch,Blake F, AU - Berry,Suzanne E, Y1 - 2012/12/27/ PY - 2013/1/4/entrez PY - 2013/1/4/pubmed PY - 2013/2/9/medline SP - 68 EP - 80 JF - Stem cells translational medicine JO - Stem Cells Transl Med VL - 2 IS - 1 N2 - Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy. DMD patients lack dystrophin protein and develop skeletal muscle pathology and dilated cardiomyopathy (DCM). Approximately 20% succumb to cardiac involvement. We hypothesized that mesoangioblast stem cells (aorta-derived mesoangioblasts [ADMs]) would restore dystrophin and alleviate or prevent DCM in animal models of DMD. ADMs can be induced to express cardiac markers, including Nkx2.5, cardiac tropomyosin, cardiac troponin I, and α-actinin, and adopt cardiomyocyte morphology. Transplantation of ADMs into the heart of mdx/utrn(-/-) mice prior to development of DCM prevented onset of cardiomyopathy, as measured by echocardiography, and resulted in significantly higher CD31 expression, consistent with new vessel formation. Dystrophin-positive cardiomyocytes and increased proliferation of endogenous Nestin(+) cardiac stem cells were detected in ADM-injected heart. Nestin(+) striated cells were also detected in four of five mdx/utrn(-/-) hearts injected with ADMs. In contrast, when ADMs were injected into the heart of aged mdx mice with advanced fibrosis, no functional improvement was detected by echocardiography. Instead, ADMs exacerbated some features of DCM. No dystrophin protein, increase in CD31 expression, or increase in Nestin(+) cell proliferation was detected following ADM injection in aged mdx heart. Dystrophin was observed following transplantation of ADMs into the hearts of young mdx mice, however, suggesting that pathology in aged mdx heart may alter the fate of donor stem cells. In summary, ADMs delay or prevent development of DCM in dystrophin-deficient heart, but timing of stem cell transplantation may be critical for achieving benefit with cell therapy in DMD cardiac muscle. SN - 2157-6564 UR - https://www.unboundmedicine.com/medline/citation/23283493/Injection_of_vessel_derived_stem_cells_prevents_dilated_cardiomyopathy_and_promotes_angiogenesis_and_endogenous_cardiac_stem_cell_proliferation_in_mdx/utrn_/__but_not_aged_mdx_mouse_models_for_duchenne_muscular_dystrophy_ L2 - https://doi.org/10.5966/sctm.2012-0107 DB - PRIME DP - Unbound Medicine ER -