What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
Abstract:MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or prim… Show more
“…As suggested in some previous studies, both UCMSCs and WJMSCs are great prototypes of MSCs with strong immune modulation and low immunogenicity (Barcia et al, 2015;Li et al, 2014;Weiss et al, 2008). Barcia et al (2015) demonstrated that UCMSCs were less immunogenic and showed higher immunosuppressive activity than BMMSCs (Barcia et al, 2015). In fact, Barcia et al showed that UCMSCs, compared to BMMSCs, show decreased expression of HLA-DRA, HO-1, IGFBP-1, -4 and -6, ILR1, IL6R, and PTGES; however, they show increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2 (Barcia et al, 2015).…”
Section: Discussionmentioning
confidence: 87%
“…This also means that Modulatists are a heterogenous MSC population that exhibits properties of both UCMSCs and Wharton's jelly-derived MSCs (WJMSCs). As suggested in some previous studies, both UCMSCs and WJMSCs are great prototypes of MSCs with strong immune modulation and low immunogenicity (Barcia et al, 2015;Li et al, 2014;Weiss et al, 2008). Barcia et al (2015) demonstrated that UCMSCs were less immunogenic and showed higher immunosuppressive activity than BMMSCs (Barcia et al, 2015).…”
Section: Discussionmentioning
confidence: 90%
“…Barcia et al (2015) demonstrated that UCMSCs were less immunogenic and showed higher immunosuppressive activity than BMMSCs (Barcia et al, 2015). In fact, Barcia et al showed that UCMSCs, compared to BMMSCs, show decreased expression of HLA-DRA, HO-1, IGFBP-1, -4 and -6, ILR1, IL6R, and PTGES; however, they show increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2 (Barcia et al, 2015). WJMSCs are also a great source of MSCs; several previous publications have shown that WJMSCs exert strong suppression on lymphocyte proliferation and have low immunogenicity (Weiss et al, 2008;Zhou et al, 2011).…”
Abstract-Introduction:Mesenchymal stem cells (MSCs) show great promise in regenerative medicine. Clinical applications of MSCs have recently increased significantly, especially for immune diseases. Autologous transplantation is considered a safe therapy. However, its main disadvantages are poor stability and quality of MSCs from patient to patient, and labor-intensive and time-consuming culture procedures. Therefore, allogeneic MSC transplantation has recently emerged as a potential replacement for autologous transplantation. "Off the shelf" MSC products, or socalled "stem cell drugs", have rapidly developed; these products have already been approved in various countries, including Canada, Korea and Japan. This study aims to evaluate a new stem cell product or "drug", termed Modulatist TM , derived from umbilical cord mesenchymal stem cells (UCMSCs), which have strong immunomodulatory properties, compared to bone marrow-derived MSCs (BMMSCs) or adipose tissue-derived stem cells (ADSCs). Methods: Modulatist TM was produced from MSCs derived from whole umbilical cord (UC) tissue (which includes Wharton's jelly and UC), according to GMP compliant procedures. Bone marrow-and adipose tissue-derived MSCs were isolated and proliferated in standard conditions, according to GMP compliant procedures. Immunomodulation mediated by MSCs was assessed by allogenic T cell suppression and cytokine release; role of prostaglandin E2 in the immunomodulation was also evaluated. Results: The results showed that Modulatist TM exhibited stronger immunomodulation than BMMSC and ADSC in vitro. Modulatist TM strongly suppressed allogeneic T cells proliferation and decreased cytokine production, compared to BMMSCs and ADSCs. Conclusion: Modulatist TM is a strong immunomodulator and promising MSC product. It may be useful to modulate or treat autoimmune diseases.
“…As suggested in some previous studies, both UCMSCs and WJMSCs are great prototypes of MSCs with strong immune modulation and low immunogenicity (Barcia et al, 2015;Li et al, 2014;Weiss et al, 2008). Barcia et al (2015) demonstrated that UCMSCs were less immunogenic and showed higher immunosuppressive activity than BMMSCs (Barcia et al, 2015). In fact, Barcia et al showed that UCMSCs, compared to BMMSCs, show decreased expression of HLA-DRA, HO-1, IGFBP-1, -4 and -6, ILR1, IL6R, and PTGES; however, they show increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2 (Barcia et al, 2015).…”
Section: Discussionmentioning
confidence: 87%
“…This also means that Modulatists are a heterogenous MSC population that exhibits properties of both UCMSCs and Wharton's jelly-derived MSCs (WJMSCs). As suggested in some previous studies, both UCMSCs and WJMSCs are great prototypes of MSCs with strong immune modulation and low immunogenicity (Barcia et al, 2015;Li et al, 2014;Weiss et al, 2008). Barcia et al (2015) demonstrated that UCMSCs were less immunogenic and showed higher immunosuppressive activity than BMMSCs (Barcia et al, 2015).…”
Section: Discussionmentioning
confidence: 90%
“…Barcia et al (2015) demonstrated that UCMSCs were less immunogenic and showed higher immunosuppressive activity than BMMSCs (Barcia et al, 2015). In fact, Barcia et al showed that UCMSCs, compared to BMMSCs, show decreased expression of HLA-DRA, HO-1, IGFBP-1, -4 and -6, ILR1, IL6R, and PTGES; however, they show increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2 (Barcia et al, 2015). WJMSCs are also a great source of MSCs; several previous publications have shown that WJMSCs exert strong suppression on lymphocyte proliferation and have low immunogenicity (Weiss et al, 2008;Zhou et al, 2011).…”
Abstract-Introduction:Mesenchymal stem cells (MSCs) show great promise in regenerative medicine. Clinical applications of MSCs have recently increased significantly, especially for immune diseases. Autologous transplantation is considered a safe therapy. However, its main disadvantages are poor stability and quality of MSCs from patient to patient, and labor-intensive and time-consuming culture procedures. Therefore, allogeneic MSC transplantation has recently emerged as a potential replacement for autologous transplantation. "Off the shelf" MSC products, or socalled "stem cell drugs", have rapidly developed; these products have already been approved in various countries, including Canada, Korea and Japan. This study aims to evaluate a new stem cell product or "drug", termed Modulatist TM , derived from umbilical cord mesenchymal stem cells (UCMSCs), which have strong immunomodulatory properties, compared to bone marrow-derived MSCs (BMMSCs) or adipose tissue-derived stem cells (ADSCs). Methods: Modulatist TM was produced from MSCs derived from whole umbilical cord (UC) tissue (which includes Wharton's jelly and UC), according to GMP compliant procedures. Bone marrow-and adipose tissue-derived MSCs were isolated and proliferated in standard conditions, according to GMP compliant procedures. Immunomodulation mediated by MSCs was assessed by allogenic T cell suppression and cytokine release; role of prostaglandin E2 in the immunomodulation was also evaluated. Results: The results showed that Modulatist TM exhibited stronger immunomodulation than BMMSC and ADSC in vitro. Modulatist TM strongly suppressed allogeneic T cells proliferation and decreased cytokine production, compared to BMMSCs and ADSCs. Conclusion: Modulatist TM is a strong immunomodulator and promising MSC product. It may be useful to modulate or treat autoimmune diseases.
“…Our results are in accordance to published data, revealing that immune-related markers CD200, CD273 and CD274 are differently expressed on MSCs depending on the tissue of origin and that, among the different MSC sources, UCT-MSCs express these markers in the greatest proportion. These differences may affect the immunological properties of each MSCs population and may explain the lower immunogenicity of UCT-MSCs compared to MSCs derived from other sources [18]. On the other hand, it is worth noting that BM-MSCs may have a putative advantage in terms of low immunogenicity as compared to AT-MSCs, due to relevant expression of at least the CD274 antigen.Fig.…”
BackgroundMesenchymal stromal cells (MSCs) have been largely investigated, in the past decade, as potential therapeutic strategies for various acute and chronic pathological conditions. MSCs isolated from different sources, such as bone marrow (BM), umbilical cord tissue (UCT) and adipose tissue (AT), share many biological features, although they may show some differences on cumulative yield, proliferative ability and differentiation potential. The standardization of MSCs growth and their functional amplification is a mandatory objective of cell therapies. The aim of this study was to evaluate the cumulative yield and the ex vivo amplification potential of MSCs obtained from various sources and different subjects, using defined culture conditions with a standardized platelet lysate (PL) as growth stimulus.MethodsMSCs isolated from BM, UCT and AT and expanded in human PL were compared in terms of cumulative yield and growth potential per gram of starting tissue. MSCs morphology, phenotype, differentiation potential, and immunomodulatory properties were also investigated to evaluate their biological characteristics.ResultsThe use of standardized PL-based culture conditions resulted in a very low variability of MSC growth. Our data showed that AT has the greater capacity to generate MSC per gram of initial tissue, compared to BM and UCT. However, UCT-MSCs replicated faster than AT-MSCs and BM-MSCs, revealing a greater proliferation capacity of this source irrespective of its lower MSC yield. All MSCs exhibited the typical MSC phenotype and the ability to differentiate into all mesodermal lineages, while BM-MSCs showed the most prominent immunosuppressive effect in vitro.ConclusionsThe adoption of standardized culture conditions may help researchers and clinicians to reveal particular characteristics and inter-individual variability of MSCs sourced from different tissues. These data will be beneficial to set the standards for tissue collection and MSCs clinical-scale expansion both for cell banking and for cell-based therapy settings.
“…Several studies have detected increased levels of TGF-α together with other cytokines in the mesenchymal stem cells derived from the umbilical cord in comparison with the cells derived from bone marrow suggesting their immunosuppressive properties [6,20]. TGF-α seemingly is an important growth factor for extraembryonic tissue development.…”
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