generation-mesenchymal-stem-cells-from-human-umbilical-cord-tissue

Generation of Mesenchymal Stem Cells from Human Umbilical Cord Tissue and their Differentiation into the Skeletal Muscle Lineage

Exploring the therapeutic potential of mesenchymal stem cells is contingent upon the ease of isolation, potency toward differentiation, and the ...

NCR Biotech Science Cluster

Skeletal muscle atrophy or wasting accompanies various chronic illnesses and the aging process, thereby reducing muscle function. One of the most important components contributing to effective muscle repair in postnatal organisms, the satellite cells (SCs), have recently become the focus of several studies examining factors participating in the atrophic process. We critically examine here the experimental evidence linking SC function with muscle loss in connection with various diseases as well as aging, and in the subsequent recovery process. Several recent reports have investigated the changes in SCs in terms of their differentiation and proliferative capacity in response to various atrophic stimuli. In this regard, we review the molecular changes within SCs that contribute to their dysfunctional status in atrophy, with the intention of shedding light on novel potential pharmacological targets to counteract the loss of muscle mass. 

The quasi-parallel lives of satellite cells and atrophying muscle.

Although skeletal muscle wasting has long been observed as a clinical outcome of impaired vitamin D signaling, precise molecular mechanisms that mediate the loss of muscle mass in the absence of vitamin D signaling are less clear. To determine the molecular consequences of vitamin D signaling, we analyzed the role of signal transducer and activator of transcription 3 (Stat3) signaling, a known contributor to various muscle wasting pathologies, in skeletal muscles.

Inhibition of Stat3 signaling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor.

Skeletal muscle constitutes more than 30% of total body mass using substrates such as glycogen, glucose, free fatty acids, and creatinine phosphate to generate energy. Consequently, multinucleated myofibers and resident mononucleated stem cells (satellite cells) generate several metabolites, which enter into circulation affecting the function of other organs, especially during exercise and atrophy. The present study was aimed at building a comprehensive profile of metabolites in primary human skeletal muscle cells during myogenic progression in an untargeted metabolomics approach using a high resolution Orbitrap Fusion Tribrid Mass Spectrometer. Identification of metabolites with multivariate statistical analyses showed a global shift in metabolomic profiles between myoblasts undergoing proliferation and differentiation along with distinctly separable profiles between early and late differentiating cultures. Pathway analyses of 71 unique metabolites revealed that Pantothenate metabolism and Coenzyme A biosynthesis and Arginine Proline metabolism play dominant roles in proliferating myoblasts, while metabolites involved in vitamin B6, Glyoxylate and Dicarboxylate, Nitrogen, Glutathione, and Tryptophan metabolism were upregulated during differentiation. We found that early and late differentiating cultures displayed differences in Phenylalanine, Tyrosine, Glycine, Serine and Threonine metabolism. Our results identify metabolites during maturation of muscle from progenitor myoblasts that have implications in muscle regeneration and pathophysiology.

Metabolomic analysis of primary human skeletal muscle cells during myogenic progression.

Differentiation of mesenchymal stem cells (MSCs) derived from two different sources of fetal tissues such as umbilical cord blood (UCB) and tissue (UCT) into skeletal muscle have remained underexplored. Here, we present a comparative analysis of UCB and UCT MSCs, in terms of surface markers, proliferation and senescence marker expression. We find that CD45CD34 MSCs obtained from UCT and UCB of term births display differences in the combinatorial expression of key MSC markers CD105 and CD90. Importantly, UCT MSCs display greater yield, higher purity, shorter culture time, and lower rates of senescence in culture compared to UCB MSCs. Using a robust myogenic differentiation protocol, we show that UCT MSCs differentiate more robustly into muscle than UCB MSCs by transcriptomic sequencing and specific myogenic markers. Functional assays reveal that CD90, and not CD105 expression promotes myogenic differentiation in MSCs and could explain the enhanced myogenic potential of UCT MSCs. These results suggest that in comparison to large volumes of UCB that are routinely used to obtain MSCs and with limited success, UCT is a more reliable, robust, and convenient source of MSCs to derive cells of the myogenic lineage for both therapeutic purposes and increasing our understanding of developmental processes.

Umbilical cord tissue is a robust source for mesenchymal stem cells with enhanced myogenic differentiation potential compared to cord blood.

Defining events: 2020 in hindsight.

Publisher Correction: Umbilical cord tissue is a robust source for mesenchymal stem cells with enhanced myogenic differentiation potential compared to cord blood.

Article	Year
The quasi-parallel lives of satellite cells and atrophying muscle. Frontiers in aging neuroscience\| PubMed ID: 26257645	2015
Inhibition of Stat3 signaling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor. Skeletal muscle\| PubMed ID: 28122601	2017
Metabolomic analysis of primary human skeletal muscle cells during myogenic progression. Scientific reports\| PubMed ID: 32678274	2020
Umbilical cord tissue is a robust source for mesenchymal stem cells with enhanced myogenic differentiation potential compared to cord blood. Scientific reports\| PubMed ID: 33149204	2020
Defining events: 2020 in hindsight. Science (New York, N.Y.)\| PubMed ID: 33384362	2021
Publisher Correction: Umbilical cord tissue is a robust source for mesenchymal stem cells with enhanced myogenic differentiation potential compared to cord blood. Scientific reports\| PubMed ID: 34188158	2021

Suchitra D. Gopinath

Biography

JoVE Journal Publications

Other Publications