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Case Report

Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy

1
Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences, Laboratory of Biology of Stem and Neoplastic Cells, 53-114 Wroclaw, Poland
2
Institute of Human Genetics of the Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, 60-479 Poznan, Poland
3
Hospital MedPolonia, 60-693 Poznan, Poland
4
Private Practice NeuroTeam, 60-539 Poznan, Poland
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(5), 1119; https://doi.org/10.3390/cells9051119
Received: 11 February 2020 / Revised: 23 April 2020 / Accepted: 28 April 2020 / Published: 30 April 2020
Duchenne muscular dystrophy (DMD) is a genetic disorder associated with a progressive deficiency of dystrophin that leads to skeletal muscle degeneration. In this study, we tested the hypothesis that a co-transplantation of two stem/progenitor cell populations, namely bone marrow-derived mesenchymal stem cells (BM-MSCs) and skeletal muscle-derived stem/progenitor cells (SM-SPCs), directly into the dystrophic muscle can improve the skeletal muscle function of DMD patients. Three patients diagnosed with DMD, confirmed by the dystrophin gene mutation, were enrolled into a study approved by the local Bioethics Committee (no. 79/2015). Stem/progenitor cells collected from bone marrow and skeletal muscles of related healthy donors, based on HLA matched antigens, were expanded in a closed MC3 cell culture system. A simultaneous co-transplantation of BM-MSCs and SM-SPCs was performed directly into the biceps brachii (two patients) and gastrocnemius (one patient). During a six-month follow-up, the patients were examined with electromyography (EMG) and monitored for blood kinase creatine level. Muscle biopsies were examined with histology and assessed for dystrophin at the mRNA and protein level. A panel of 27 cytokines was analysed with multiplex ELISA. We did not observe any adverse effects after the intramuscular administration of cells. The efficacy of BM-MSC and SM-SPC application was confirmed through an EMG assessment by an increase in motor unit parameters, especially in terms of duration, amplitude range, area, and size index. The beneficial effect of cellular therapy was confirmed by a decrease in creatine kinase levels and a normalised profile of pro-inflammatory cytokines. BM-MSCs may support the pro-regenerative potential of SM-SPCs thanks to their trophic, paracrine, and immunomodulatory activity. Both applied cell populations may fuse with degenerating skeletal muscle fibres in situ, facilitating skeletal muscle recovery. However, further studies are required to optimise the dose and timing of stem/progenitor cell delivery. View Full-Text
Keywords: Duchenne muscular dystrophy (DMD); mesenchymal stem cells (MSCs); skeletal muscle stem/progenitor cells (SM-SPCs); cellular therapy of DMD; co-transplantation Duchenne muscular dystrophy (DMD); mesenchymal stem cells (MSCs); skeletal muscle stem/progenitor cells (SM-SPCs); cellular therapy of DMD; co-transplantation
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MDPI and ACS Style

Klimczak, A.; Zimna, A.; Malcher, A.; Kozlowska, U.; Futoma, K.; Czarnota, J.; Kemnitz, P.; Bryl, A.; Kurpisz, M. Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy. Cells 2020, 9, 1119. https://doi.org/10.3390/cells9051119

AMA Style

Klimczak A, Zimna A, Malcher A, Kozlowska U, Futoma K, Czarnota J, Kemnitz P, Bryl A, Kurpisz M. Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy. Cells. 2020; 9(5):1119. https://doi.org/10.3390/cells9051119

Chicago/Turabian Style

Klimczak, Aleksandra, Agnieszka Zimna, Agnieszka Malcher, Urszula Kozlowska, Katarzyna Futoma, Jaroslaw Czarnota, Pawel Kemnitz, Anna Bryl, and Maciej Kurpisz. 2020. "Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy" Cells 9, no. 5: 1119. https://doi.org/10.3390/cells9051119

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