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Cardiac Protection after Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the mdx Mouse Model of Duchenne Muscular Dystrophy.
Stem Cell Rev Rep. 2019 12; 15(6):827-841.SC

Abstract

Duchenne Muscular Dystrophy (DMD) is a progressive lethal disease caused by X-linked mutations of the dystrophin gene. Dystrophin deficiency clinically manifests as skeletal and cardiac muscle weakness, leading to muscle wasting and premature death due to cardiac and respiratory failure. Currently, no cure exists. Since heart disease is becoming a leading cause of death in DMD patients, there is an urgent need to develop new more effective therapeutic strategies for protection and improvement of cardiac function. We previously reported functional improvements correlating with dystrophin restoration following transplantation of Dystrophin Expressing Chimeric Cells (DEC) of myoblast origin in the mdx and mdx/scid mouse models. Here, we confirm positive effect of DEC of myoblast (MBwt/MBmdx) and mesenchymal stem cells (MBwt/MSCmdx) origin on protection of cardiac function after systemic DEC transplant. Therapeutic effect of DEC transplant (0.5 × 106) was assessed by echocardiography at 30 and 90 days after systemic-intraosseous injection to the mdx mice. At 90 days post-transplant, dystrophin expression in cardiac muscles of DEC injected mice significantly increased (15.73% ± 5.70 -MBwt/MBmdx and 5.22% ± 1.10 - MBwt/MSCmdx DEC) when compared to vehicle injected controls (2.01% ± 1.36) and, correlated with improved ejection fraction and fractional shortening on echocardiography. DEC lines of MB and MSC origin introduce a new promising approach based on the combined effects of normal myoblasts with dystrophin delivery capacities and MSC with immunomodulatory properties. Our study confirms feasibility and efficacy of DEC therapy on cardiac function and represents a novel therapeutic strategy for cardiac protection and muscle regeneration in DMD.

Authors+Show Affiliations

Department of Surgery, Poznan University of Medical Sciences, Poznan, Poland. siemiom@hotmail.com. Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, 60612, USA. siemiom@hotmail.com.Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, 60612, USA.Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, 60612, USA.Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, 60612, USA.Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, 60612, USA.Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA. Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA.

Pub Type(s)

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

Language

eng

PubMed ID

31612351

Citation

Siemionow, Maria, et al. "Cardiac Protection After Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the Mdx Mouse Model of Duchenne Muscular Dystrophy." Stem Cell Reviews and Reports, vol. 15, no. 6, 2019, pp. 827-841.
Siemionow M, Malik M, Langa P, et al. Cardiac Protection after Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the mdx Mouse Model of Duchenne Muscular Dystrophy. Stem cell reviews and reports. 2019;15(6):827-841.
Siemionow, M., Malik, M., Langa, P., Cwykiel, J., Brodowska, S., & Heydemann, A. (2019). Cardiac Protection after Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the mdx Mouse Model of Duchenne Muscular Dystrophy. Stem Cell Reviews and Reports, 15(6), 827-841. https://doi.org/10.1007/s12015-019-09916-0
Siemionow M, et al. Cardiac Protection After Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the Mdx Mouse Model of Duchenne Muscular Dystrophy. Stem cell reviews and reports. 2019;15(6):827-841. PubMed PMID: 31612351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac Protection after Systemic Transplant of Dystrophin Expressing Chimeric (DEC) Cells to the mdx Mouse Model of Duchenne Muscular Dystrophy. AU - Siemionow,Maria, AU - Malik,M, AU - Langa,P, AU - Cwykiel,J, AU - Brodowska,S, AU - Heydemann,A, PY - 2019/10/16/pubmed PY - 2020/8/5/medline PY - 2019/10/16/entrez KW - (<10): Duchenne muscular dystrophy KW - Cardiac protection KW - DEC therapy KW - Dystrophin expressing chimeric (DEC) cells KW - Echocardiography KW - MSC KW - Myoblasts KW - Stem cells KW - Systemic DEC transplant KW - mdx mice SP - 827 EP - 841 JF - Stem cell reviews and reports VL - 15 IS - 6 N2 - Duchenne Muscular Dystrophy (DMD) is a progressive lethal disease caused by X-linked mutations of the dystrophin gene. Dystrophin deficiency clinically manifests as skeletal and cardiac muscle weakness, leading to muscle wasting and premature death due to cardiac and respiratory failure. Currently, no cure exists. Since heart disease is becoming a leading cause of death in DMD patients, there is an urgent need to develop new more effective therapeutic strategies for protection and improvement of cardiac function. We previously reported functional improvements correlating with dystrophin restoration following transplantation of Dystrophin Expressing Chimeric Cells (DEC) of myoblast origin in the mdx and mdx/scid mouse models. Here, we confirm positive effect of DEC of myoblast (MBwt/MBmdx) and mesenchymal stem cells (MBwt/MSCmdx) origin on protection of cardiac function after systemic DEC transplant. Therapeutic effect of DEC transplant (0.5 × 106) was assessed by echocardiography at 30 and 90 days after systemic-intraosseous injection to the mdx mice. At 90 days post-transplant, dystrophin expression in cardiac muscles of DEC injected mice significantly increased (15.73% ± 5.70 -MBwt/MBmdx and 5.22% ± 1.10 - MBwt/MSCmdx DEC) when compared to vehicle injected controls (2.01% ± 1.36) and, correlated with improved ejection fraction and fractional shortening on echocardiography. DEC lines of MB and MSC origin introduce a new promising approach based on the combined effects of normal myoblasts with dystrophin delivery capacities and MSC with immunomodulatory properties. Our study confirms feasibility and efficacy of DEC therapy on cardiac function and represents a novel therapeutic strategy for cardiac protection and muscle regeneration in DMD. SN - 2629-3277 UR - https://www.unboundmedicine.com/medline/citation/31612351/Cardiac_Protection_after_Systemic_Transplant_of_Dystrophin_Expressing_Chimeric__DEC__Cells_to_the_mdx_Mouse_Model_of_Duchenne_Muscular_Dystrophy_ L2 - https://doi.org/10.1007/s12015-019-09916-0 DB - PRIME DP - Unbound Medicine ER -