Human mesenchymal stromal cells (MSCs) are currently the leading candidate for cell-based therapeutics. While the use of MSCs in transplantation therapies is widely expanding, still, there is a lot of scope for better understanding of the mechanisms underlying their effects. We have generated MSCs from pre- and post-natal human tissue sources such as Wharton's jelly (WJ), stem cells from human exfoliated deciduous teeth (SHED), and bone marrow (BM). We then expanded, banked, and characterized them based on morphology, growth kinetics, senescence, immunophenotype, gene expression, and secretion of growth factors. Although the immunophenotype was very similar across MSCs from the three types of donor tissues, they showed minor variations in their growth kinetics. Further, a higher percentage of senescent cells were observed in BM-MSCs than in WJ-MSCs and SHED. Gene expression analysis showed the increased expression of INF-γ, PDGFA, VEGF, IL10, and SDF in SHED over WJ-MSC and BM-MSC. Comparative secretome profiling by ELISA demonstrated the presence of FGF-2, IL-10, PDGF, SDF-1, Ang-1, TGF-β3, HGF, INF-γ, VEGF, and IL-6 in cell culture supernatants. Based on our findings, WJ-MSC and SHED appear more potent than BM-MSC for managing inflammation, immunomodulation, angiogenesis, fibrosis, and scarring. Due to widespread application of MSCs in cell replacement therapy, these subtle differences need to be taken into consideration while designing stem cell-based clinical trials.
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http://dx.doi.org/10.1007/s11626-020-00501-1 | DOI Listing |
Stem Cell Res Ther
January 2025
IRMB, Univ Montpellier, INSERM, CHU St Eloi, 80 AV A Fliche, 34295-Cedex-05, Montpellier, France.
Background: The regenerative potential of mesenchymal stromal/stem cells (MSCs) has been extensively studied in clinical trials in the past decade. However, despite the promising regenerative properties documented in preclinical studies, for instance in osteoarthritis (OA), the therapeutic translation of these results in patients has not been fully conclusive. One factor contributing to this therapeutic barrier could be the presence of senescent cells in OA joints.
View Article and Find Full Text PDFPediatr Res
January 2025
Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
Cell therapies as treatments for neonatal conditions have attracted significant research and parent interest over the last two decades. Mesenchymal stromal cells, umbilical cord blood cells and neural stem cells translate from lab, to preclinical and into clinical trials, with contributions being made from all over the world. Effective and timely translation involves frequent reflection and consultation from research-adjacent fields (i.
View Article and Find Full Text PDFTissue Eng Part C Methods
January 2025
Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Scaffold-free tissue engineering strategies using cellular aggregates, microtissues, or organoids as "biological building blocks" could potentially be used for the engineering of scaled-up articular cartilage or endochondral bone-forming grafts. Such approaches require large numbers of cells; however, little is known about how different chondrogenic growth factor stimulation regimes during cellular expansion and differentiation influence the capacity of cellular aggregates or microtissues to fuse and generate hyaline cartilage. In this study, human bone marrow mesenchymal stem/stromal cells (MSCs) were additionally stimulated with bone morphogenetic protein 2 (BMP-2) and/or transforming growth factor (TGF)-β1 during both monolayer expansion and subsequent chondrogenic differentiation in a microtissue format.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Sarcoma (SARC), a diverse group of stromal tumors arising from mesenchymal tissues, is often associated with a poor prognosis. Emerging evidence indicates that senescent cells within the tumor microenvironment (TME) significantly contribute to cancer progression and metastasis. Although the influence of senescence on SARC has been partially acknowledged, it has yet to be fully elucidated.
View Article and Find Full Text PDFExtracell Vesicles Circ Nucl Acids
November 2024
Laboratorio di Biotecnologie Applicate all'Ortopedia, IRCCS Ospedale Galeazzi - Sant'Ambrogio, Milano 20157, Italy.
Mesenchymal stromal cells (MSCs) showed promising potential for regenerative and therapeutic applications for several pathologies and conditions. Their potential is mainly ascribed to the factors and extracellular vesicles (EVs) they release, which are now envisioned as cell-free therapeutics in cutting-edge clinical studies. A main cornerstone is the preferential uptake by target cells and tissues, in contrast to clearance by phagocytic cells or removal from circulation before reaching the final destination.
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