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Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy.
Stem Cell Rev Rep. 2018 Jun; 14(3):370-384.SC

Abstract

Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD. We introduce two Dystrophin Expressing Chimeric (DEC) cell lines created by ex vivo fusion of human myoblasts (MB) derived from two normal donors (MBN1/MBN2), and normal and DMD donors (MBN/MBDMD). The efficacy of fusion was confirmed by flow cytometry and confocal microscopy based on donor cell fluorescent labeling (PKH26/PKH67). In vitro, DEC displayed phenotype and genotype of donor parent cells, expressed dystrophin, and maintained proliferation and myogenic differentiation. In vivo, local delivery of both DEC lines (0.5 × 106) restored dystrophin expression (17.27%±8.05-MBN1/MBN2 and 23.79%±3.82-MBN/MBDMD) which correlated with significant improvement of muscle force, contraction and tolerance to fatigue at 90 days after DEC transplant to the gastrocnemius muscles (GM) of dystrophin-deficient mdx/scid mice. This study establishes DEC as a potential therapy for DMD and other types of muscular dystrophies.

Authors+Show Affiliations

Department of Surgery, Poznan University of Medical Sciences, Poznan, Poland. siemiom@hotmail.com. Depatment of Orthopedics, University of Illinois at Chicago, Chicago, IL, USA. siemiom@hotmail.com.Depatment of Orthopedics, University of Illinois at Chicago, Chicago, IL, USA.Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA.Department of Clinical Health Sciences, Saint Louis University, Saint Louis, MO, USA.Depatment of Orthopedics, University of Illinois at Chicago, Chicago, IL, USA.Depatment of Orthopedics, University of Illinois at Chicago, Chicago, IL, USA.Depatment of Orthopedics, University of Illinois at Chicago, Chicago, IL, USA.

Pub Type(s)

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

Language

eng

PubMed ID

29546607

Citation

Siemionow, Maria, et al. "Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy." Stem Cell Reviews and Reports, vol. 14, no. 3, 2018, pp. 370-384.
Siemionow M, Cwykiel J, Heydemann A, et al. Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy. Stem cell reviews and reports. 2018;14(3):370-384.
Siemionow, M., Cwykiel, J., Heydemann, A., Garcia, J., Marchese, E., Siemionow, K., & Szilagyi, E. (2018). Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy. Stem Cell Reviews and Reports, 14(3), 370-384. https://doi.org/10.1007/s12015-018-9807-z
Siemionow M, et al. Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy. Stem cell reviews and reports. 2018;14(3):370-384. PubMed PMID: 29546607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy. AU - Siemionow,Maria, AU - Cwykiel,Joanna, AU - Heydemann,Ahlke, AU - Garcia,Jesus, AU - Marchese,Enza, AU - Siemionow,Krzysztof, AU - Szilagyi,Erzsebet, PY - 2018/3/17/pubmed PY - 2018/12/12/medline PY - 2018/3/17/entrez KW - DEC therapy KW - DMD KW - Duchenne muscular dystrophy KW - Dystrophin KW - Dystrophin expressing chimeric human cells KW - Ex vivo cell fusion KW - Mdx/scid mice KW - Myoblasts KW - Stem cells KW - Transplant SP - 370 EP - 384 JF - Stem cell reviews and reports VL - 14 IS - 3 N2 - Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD. We introduce two Dystrophin Expressing Chimeric (DEC) cell lines created by ex vivo fusion of human myoblasts (MB) derived from two normal donors (MBN1/MBN2), and normal and DMD donors (MBN/MBDMD). The efficacy of fusion was confirmed by flow cytometry and confocal microscopy based on donor cell fluorescent labeling (PKH26/PKH67). In vitro, DEC displayed phenotype and genotype of donor parent cells, expressed dystrophin, and maintained proliferation and myogenic differentiation. In vivo, local delivery of both DEC lines (0.5 × 106) restored dystrophin expression (17.27%±8.05-MBN1/MBN2 and 23.79%±3.82-MBN/MBDMD) which correlated with significant improvement of muscle force, contraction and tolerance to fatigue at 90 days after DEC transplant to the gastrocnemius muscles (GM) of dystrophin-deficient mdx/scid mice. This study establishes DEC as a potential therapy for DMD and other types of muscular dystrophies. SN - 2629-3277 UR - https://www.unboundmedicine.com/medline/citation/29546607/Dystrophin_Expressing_Chimeric__DEC__Human_Cells_Provide_a_Potential_Therapy_for_Duchenne_Muscular_Dystrophy_ L2 - https://doi.org/10.1007/s12015-018-9807-z DB - PRIME DP - Unbound Medicine ER -