Differentiation potential of adult human MSCs into neuro-striated muscle cells

Abstract: Skeletal muscle represents one of the most abundant tissues in the human body which possesses the ability to regenerate itself in case of tissue injury or tissue loss. However, volumetric muscle loss seen with substantial traumatic injuries, radical tumor resection or nerve injury exceeds the inherent regenerative capacity of skeletal muscle. Current treatments for volumetric muscle loss have mostly been focused on autologous muscle transplantations and physical therapy with often disappointing results. In contrast, novel approaches based on cell therapy have used various substances such as horse serum or complex mixtures of growth factors to induce striated muscle differentiation in mesenchymal stem cells. However, none of the approaches are feasible for clinical applicability.
We hypothesized that Nutlin, a clinically available small p53-stimulating molecule with possible neuromuscular regenerating effects, in combination with basic fibroblast growth factor (bFGF) may offer a novel approach to stimulate (neuro)muscular differentiation in adult progenitor cells. Bone-marrow derived MSCs were first expanded in xenogenic-free expansion medium containing 5% human plasma (P) and 5% pooled platelet lysate (PL) referred to as (P/PL) and then differentiated for 0-28 days with P/PL, human bFGF (10 ng/mL), Nutlin (0.25 - 1 μM) with and without bFGF (10 ng/mL) and/or PDGF (5 ng/mL). Differentiation of MSCs was compared to commonly used methods of differentiating adipose MSCs or ucMSCs using horse serum. Differentiation of MSCs into (neuro)striated muscle cells was assessed by measuring the gene and/or protein expression of myogenic (MyoG, ACTA1, Myf5, Desmin, Myef2) and neurogenic markers (Coronin 1b, GAP-43). While our data showed that neither horse serum nor the other treatment regimens investigated here resulted in a significant increase in expression of myogenic and neurogenic markers, the differentiation of MSCs in human P/PL resulted in higher protein expression levels of neurogenic marker GAP-43, as well as Desmin and Myef2 myogenic markers. This study suggests that xenogenic-free medium containing P/PL may drive human bmMSCs into an early or primed muscle cell phenotype with neurogenic-like properties

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2018

Classification and Topics

• Keyword: Cells ; Striated muscle ; Mesenchymzelle

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2021
• Creator: Barisic, Dominik
• Contributor: Hart, Melanie L. ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät

Further information

• DOI: 10.6094/UNIFR/175654
• URN: urn:nbn:de:bsz:25-freidok-1756541
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:53 PM CET