{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:19:29Z","timestamp":1790831969121,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T00:00:00Z","timestamp":1588204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["N N407 121940"],"award-info":[{"award-number":["N N407 121940"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005632","name":"Narodowe Centrum Bada\u0144 i Rozwoju","doi-asserted-by":"publisher","award":["PBS3\/A7\/27\/2015"],"award-info":[{"award-number":["PBS3\/A7\/27\/2015"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells9051119","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T06:41:20Z","timestamp":1588660880000},"page":"1119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem\/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6590-4420","authenticated-orcid":false,"given":"Aleksandra","family":"Klimczak","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-4470","authenticated-orcid":false,"given":"Agnieszka","family":"Zimna","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics of the Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3433-6990","authenticated-orcid":false,"given":"Agnieszka","family":"Malcher","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics of the Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Kozlowska","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Futoma","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw","family":"Czarnota","sequence":"additional","affiliation":[{"name":"Hospital MedPolonia, 60-693 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Kemnitz","sequence":"additional","affiliation":[{"name":"Hospital MedPolonia, 60-693 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bryl","sequence":"additional","affiliation":[{"name":"Private Practice NeuroTeam, 60-539 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3275-3245","authenticated-orcid":false,"given":"Maciej","family":"Kurpisz","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics of the Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S1474-4422(03)00585-4","article-title":"Dystrophin and mutations: One gene, several proteins, multiple phenotypes","volume":"2","author":"Muntoni","year":"2003","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Taylor, P.J., Betts, G.A., Maroulis, S., Gilissen, C., Pedersen, R.L., Mowat, D.R., Johnston, H.M., and Buckley, M.F. (2010). Dystrophin gene mutation location and the risk of cognitive impairment in Duchenne muscular dystrophy. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008803"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.bbadis.2006.08.011","article-title":"Stem cell based therapies to treat muscular dystrophy","volume":"1772","author":"Price","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.molmed.2007.10.003","article-title":"New therapies for Duchenne muscular dystrophy: Challenges, prospects and clinical trials","volume":"13","author":"Cossu","year":"2007","journal-title":"Trends Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/jcp.21895","article-title":"Cell based therapy for Duchenne muscular dystrophy","volume":"221","author":"Farini","year":"2009","journal-title":"J. Cell Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.nmd.2010.10.004","article-title":"Stem cells to treat muscular dystrophies\u2014Where are we?","volume":"21","author":"Meng","year":"2011","journal-title":"Neuromuscul. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ana.410340105","article-title":"Myoblast transfer in Duchenne muscular dystrophy","volume":"34","author":"Karpati","year":"1993","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1177\/096368979300200607","article-title":"Cell transplantation as an experimental treatment for Duchenne muscular dystrophy","volume":"2","author":"Law","year":"1993","journal-title":"Cell Transplant"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1056\/NEJM199509283331303","article-title":"Myoblast transfer in the treatment of Duchenne\u2019s muscular dystrophy","volume":"333","author":"Mendell","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/(SICI)1097-4598(199704)20:4<469::AID-MUS10>3.0.CO;2-U","article-title":"Myoblast implantation in Duchenne muscular dystrophy: The San Francisco study","volume":"20","author":"Miller","year":"1997","journal-title":"Muscle Nerve"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ymthe.2003.11.023","article-title":"Dystrophin expression in myofibers of Duchenne muscular dystrophy patients following intramuscular injections of normal myogenic cells","volume":"9","author":"Skuk","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_12","first-page":"128","article-title":"Myoblast transfer therapy: Is there any light at the end of the tunnel?","volume":"24","author":"Mouly","year":"2005","journal-title":"Acta Myol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/01.jnen.0000218443.45782.81","article-title":"Dystrophin expression in muscles of duchenne muscular dystrophy patients after high-density injections of normal myogenic cells","volume":"65","author":"Skuk","year":"2006","journal-title":"J. Neuropathol Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.nmd.2006.10.003","article-title":"First test of a \u201chigh-density injection\u201d protocol for myogenic cell transplantation throughout large volumes of muscles in a Duchenne muscular dystrophy patient: Eighteen months follow-up","volume":"17","author":"Skuk","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"438675","DOI":"10.1155\/2014\/438675","article-title":"From innate to adaptive immune response in muscular dystrophies and skeletal muscle regeneration: The role of lymphocytes","volume":"2014","author":"Madaro","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00005-018-0509-7","article-title":"Muscle Stem\/Progenitor Cells and Mesenchymal Stem Cells of Bone Marrow Origin for Skeletal Muscle Regeneration in Muscular Dystrophies","volume":"66","author":"Klimczak","year":"2018","journal-title":"Arch. Immunol. Ther. Exp. (Warsz)"},{"key":"ref_17","first-page":"891972","article-title":"Systemic Inflammation in Duchenne Muscular Dystrophy: Association with Muscle Function and Nutritional Status","volume":"2015","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"347","DOI":"10.4252\/wjsc.v11.i6.347","article-title":"Similarities and differences between mesenchymal stem\/progenitor cells derived from various human tissues","volume":"11","author":"Kozlowska","year":"2019","journal-title":"World J. Stem Cells"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/00004691-199609000-00004","article-title":"Quantitative motor unit potential analysis","volume":"13","author":"Stalberg","year":"1996","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1212\/WNL.0b013e318208811f","article-title":"Muscle histology vs MRI in Duchenne muscular dystrophy","volume":"76","author":"Kinali","year":"2011","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.omtm.2017.05.002","article-title":"Cell Therapy in Myology: Dynamics of Muscle Precursor Cell Death after Intramuscular Administration in Non-human Primates","volume":"5","author":"Skuk","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1096\/fj.02-0060fje","article-title":"Cyclosporin A blocks muscle differentiation by inducing oxidative stress and inhibiting the peptidyl-prolyl-cis-trans isomerase activity of cyclophilin A: Cyclophilin A protects myoblasts from cyclosporin A-induced cytotoxicity","volume":"16","author":"Hong","year":"2002","journal-title":"FASEB J."},{"key":"ref_23","first-page":"540370","article-title":"Cytokines and chemokines as regulators of skeletal muscle inflammation: Presenting the case of Duchenne muscular dystrophy","volume":"2013","year":"2013","journal-title":"Mediators Inflamm."},{"key":"ref_24","first-page":"63","article-title":"Efficacy of stem cell therapy in ambulatory and nonambulatory children with Duchenne muscular dystrophy - Phase I-II","volume":"8","author":"Dai","year":"2018","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6093601","DOI":"10.1155\/2016\/6093601","article-title":"Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies","volume":"2016","author":"Consalvi","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1089\/scd.2017.0248","article-title":"Human Umbilical Cord Perivascular Cells and Human Bone Marrow Mesenchymal Stromal Cells Transplanted Intramuscularly Respond to a Distant Source of Inflammation","volume":"27","author":"Estrada","year":"2018","journal-title":"Stem Cells Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/cei.12445","article-title":"Cytokines in immune-mediated inflammatory myopathies: Cellular sources, multiple actions and therapeutic implications","volume":"178","author":"Moran","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s41232-016-0019-0","article-title":"Inflammatory predisposition predicts disease phenotypes in muscular dystrophy","volume":"36","author":"Takeda","year":"2016","journal-title":"Inflamm. Regen."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/cphy.c170052","article-title":"Immunobiology of Inherited Muscular Dystrophies","volume":"8","author":"Tidball","year":"2018","journal-title":"Compr. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"560629","DOI":"10.1155\/2014\/560629","article-title":"Macrophage plasticity in skeletal muscle repair","volume":"2014","author":"Rigamonti","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Benny Klimek, M.E., Sali, A., Rayavarapu, S., Van der Meulen, J.H., and Nagaraju, K. (2016). Effect of the IL-1 Receptor Antagonist Kineret(R) on Disease Phenotype in mdx Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155944"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cellimm.2009.10.006","article-title":"Mesenchymal stem cells as anti-inflammatories: Implications for treatment of Duchenne muscular dystrophy","volume":"260","author":"Ichim","year":"2010","journal-title":"Cell Immunol."},{"key":"ref_33","first-page":"8","article-title":"Cytokine expression and secretion by skeletal muscle cells: Regulatory mechanisms and exercise effects","volume":"21","author":"Peake","year":"2015","journal-title":"Exerc. Immunol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1212\/WNL.0b013e3182518302","article-title":"Increased muscle expression of interleukin-17 in Duchenne muscular dystrophy","volume":"78","author":"Verardo","year":"2012","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biomaterials.2018.04.055","article-title":"Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy","volume":"174","author":"Bier","year":"2018","journal-title":"Biomaterials"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cyto.2017.12.006","article-title":"Identification of plasma interleukins as biomarkers for deflazacort and omega-3 based Duchenne muscular dystrophy therapy","volume":"102","author":"Matsumura","year":"2018","journal-title":"Cytokine"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/5\/1119\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:52:11Z","timestamp":1760363531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/5\/1119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,30]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["cells9051119"],"URL":"https:\/\/doi.org\/10.3390\/cells9051119","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,30]]}}}