title: Stem cells isolated from human dental pulp and amniotic fluid improve skeletal muscle histopathology in mdx/SCID mice.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy. alessandra.pisciotta@unimore.it.
authors: Alessandra
authors: A
authors: Pisciotta
authors: Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy. massimo.riccio@unimore.it.
authors: Massimo
authors: M
authors: Riccio
authors: Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy. gianluca.carnevale@unimore.it.
authors: Gianluca
authors: G
authors: Carnevale
authors: Stem Cell Research Center, Department of Orthopaedic Surgery, University of Pittsburgh, 450 Technology Drive, Bridgeside Point II, Suite 206, 15219, Pittsburgh, PA, USA. ail3@pitt.edu.
authors: Aiping
authors: A
authors: Lu
authors: Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy. sara.debiasi@unimore.it.
authors: Sara
authors: S
authors: De Biasi
authors: Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy. lara.gibellini@unimore.it.
authors: Lara
authors: L
authors: Gibellini
authors: Department of Obstetrics and Gynecology, Arcispedale Santa Maria Nuova, viale Risorgimento 80, 42123, Reggio Emilia, Italy. lasala.giovanni@asmn.re.it.
authors: Giovanni B
authors: GB
authors: La Sala
authors: Oro-Maxillo-Facial Department, AUSL Baggiovara, via Giardini 1355, 41126, Modena, Baggiovara, Italy. gbruzzesi@libero.it.
authors: Giacomo
authors: G
authors: Bruzzesi
authors: Department of Biomedical, Metabolic and Neuroscience, University of Modena and Reggio Emilia, Children Rehabilitation Special Unit, IRCCS Arcispedale Santa Maria Nuova, viale Risorgimento 80, 42123, Reggio Emilia, Italy. adriano.ferrari@unimore.it.
authors: Adriano
authors: A
authors: Ferrari
authors: Stem Cell Research Center, Department of Orthopaedic Surgery, University of Pittsburgh, 450 Technology Drive, Bridgeside Point II, Suite 206, 15219, Pittsburgh, PA, USA. jhuard@pitt.edu.
authors: Johnny
authors: J
authors: Huard
authors: Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy. anto.depol@unimore.it.
authors: Anto
authors: A
authors: De Pol
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D002460:Cell Line; D003782:Dental Pulp / Q000166:cytology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018101:Mice, Inbred mdx; D016513:Mice, SCID; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000628:therapy*; D012038:Regeneration