Abstract
Mesenchymal stromal cells (MSCs) currently constitute the most frequently used cell type in advanced therapies with different purposes, most of which are related with inflammatory processes. Although the therapeutic efficacy of these cells has been clearly demonstrated in different disease animal models and in numerous human phase I/II clinical trials, only very few phase III trials using MSCs have demonstrated the expected potential therapeutic benefit. On the other hand, diverse controversial issues on the biology and clinical applications of MSCs, including their specific phenotype, the requirement of an inflammatory environment to induce immunosuppression, the relevance of the cell dose and their administration schedule, the cell delivery route (intravascular/systemic vs. local cell delivery), and the selected cell product (i.e., use of autologous vs. allogeneic MSCs, freshly cultured vs. frozen and thawed MSCs, MSCs vs. MSC-derived extracellular vesicles, etc.) persist. In the current review article, we have addressed these issues with special emphasis in the new approaches to improve the properties and functional capabilities of MSCs after distinct cell bioengineering strategies.
Highlights
Mesenchymal Stromal Cells: Lights and Shadows in the Knowledge of Their Mechanisms of ActionNumerous questions on the biology of mesenchymal stromal cells (MSCs), the most promising cell type for cell therapy strategies, remain unknown (Galipeau and Sensebe, 2018)
Anti-Mesenchymal stromal cells (MSCs) responses are lower than those against other allogeneic cells are (Khan and Newsome, 2019), perhaps because MSCs do not express MHC class II antigens or co-stimulatory molecules. The balance between their immunogenicity and the release of immunosuppressive factors, highly dependent on the local microenvironment, determines the MSC behavior (Khan and Newsome, 2019). This cytotoxic activity is important for MSCmediated immunosuppression because it results in phagocytosis of apoptotic cells and macrophage polarization (Galleu et al, 2017; de Witte et al, 2018)
On a phase III clinical trial for the treatment of complex perianal fistulous pathology in patients with Crohn’s disease, the authors carried out a study on the immunological responses and MSC efficacy taking into account the haplotypes of the donor cells and the recipient concluding that an HLA-screening to the donor MSCs would be performed to limit the humoral response between donor and recipient
Summary
Mesenchymal Stromal Cells: Lights and Shadows in the Knowledge of Their Mechanisms of Action. A current survey on the heterogeneity of MSCs, their immunogenicity, routes of delivery and migratory capacity, and principally on the mechanisms governing their immunomodulatory properties needs a substantial revision in order to design protocols for improving their therapeutic capacities, including MSC bioengineering. Multiple parameters can affect the therapeutic properties of MSCs including tissue origin (Ketterl et al, 2015), cryopreservation procedure (Oja et al, 2019), culture time and media supplementation with different growth factors (von Bahr et al, 2012; Moll et al, 2014b), optimal dosage (Golpanian et al, 2016) and in vivo cell delivery (Caplan et al, 2019; Moll et al, 2019) can affect substantially the cellular therapeutic properties of MSCs. a better knowledge of these cell processes would improve the therapeutic outcomes of MSCs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
