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Stem cells isolated from human dental pulp and amniotic fluid improve skeletal muscle histopathology in mdx/SCID mice.

Pisciotta, Alessandra and Riccio, Massimo and Carnevale, Gianluca and Lu, Aiping and De Biasi, Sara and Gibellini, Lara and La Sala, Giovanni B and Bruzzesi, Giacomo and Ferrari, Adriano and Huard, Johnny and De Pol, Anto (2015) Stem cells isolated from human dental pulp and amniotic fluid improve skeletal muscle histopathology in mdx/SCID mice. Stem Cell Res Ther, 6. 156 - ?.

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INTRODUCTION: Duchenne muscular dystrophy (DMD), caused by a lack of the functional structural protein dystrophin, leads to severe muscle degeneration where the patients are typically wheelchair-bound and die in their mid-twenties from cardiac or respiratory failure or both. The aim of this study was to investigate the potential of human dental pulp stem cells (hDPSCs) and human amniotic fluid stem cells (hAFSCs) to differentiate toward a skeletal myogenic lineage using several different protocols in order to determine the optimal conditions for achieving myogenic commitment and to subsequently evaluate their contribution in the improvement of the pathological features associated with dystrophic skeletal muscle when intramuscularly injected into mdx/SCID mice, an immune-compromised animal model of DMD. METHODS: Human DPSCs and AFSCs were differentiated toward myogenic lineage in vitro through the direct co-culture with a myogenic cell line (C2C12 cells) and through a preliminary demethylation treatment with 5-Aza-2'-deoxycytidine (5-Aza), respectively. The commitment and differentiation of both hDPSCs and hAFSCs were evaluated by immunofluorescence and Western blot analysis. Subsequently, hDPSCs and hAFSCs, preliminarily demethylated and pre-differentiated toward a myogenic lineage for 2 weeks, were injected into the dystrophic gastrocnemius muscles of mdx/SCID mice. After 1, 2, and 4 weeks, the gastrocnemius muscles were taken for immunofluorescence and histological analyses. RESULTS: Both populations of cells engrafted within the host muscle of mdx/SCID mice and through a paracrine effect promoted angiogenesis and reduced fibrosis, which eventually led to an improvement of the histopathology of the dystrophic muscle. CONCLUSION: This study shows that hAFSCs and hDPSCs represent potential sources of stem cells for translational strategies to improve the histopathology and potentially alleviate the muscle weakness in patients with DMD.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Pisciotta, Alessandra
Riccio, Massimo
Carnevale, Gianluca
Lu, Aiping
De Biasi, Sara
Gibellini, Lara
La Sala, Giovanni B
Bruzzesi, Giacomo
Ferrari, Adriano
Huard, Johnny
De Pol, Anto
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 30 July 2015
Date Type: Acceptance
Journal or Publication Title: Stem Cell Res Ther
Volume: 6
Page Range: 156 - ?
DOI or Unique Handle: 10.1186/s13287-015-0141-y
Schools and Programs: School of Medicine > Orthopaedic Surgery
Refereed: Yes
Uncontrolled Keywords: Amniotic Fluid, Animals, Cell Line, Dental Pulp, Humans, Mesenchymal Stem Cell Transplantation, Mesenchymal Stromal Cells, Mice, Mice, Inbred mdx, Mice, SCID, Muscle Development, Muscle, Skeletal, Muscular Dystrophy, Duchenne, Regeneration
Date Deposited: 09 Aug 2016 19:46
Last Modified: 20 Dec 2018 00:55


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