Table 2 Summary table of differentiated allogeneic MSC in myocardial regeneration models
Paper | Model | In vitro immunogenicity | In vitro immunosuppressive ability | In vivo engraftment | In vivo immune marker expression | In vivo functional benefits | In vivo cellular response | In vivo antibody response |
|---|---|---|---|---|---|---|---|---|
Xia and Cao [47] | Balb/C cardiomyocyte dMSCs to C57/BL6 mouse MI model | Increased MHCI and MHCII expression on cardiomyocyte dMSCs | NT | Both undifferentiated and differentiated allogeneic MSCs engrafted. Over 4Â weeks dMSCs were cleared quicker than undifferentiated | NT | Both differentiated and undifferentiated MSCs improved function at 2Â weeks over controls; however, by 4Â weeks benefit due to dMSCs was lost | CD4+ and CD8+ infiltration in both undifferentiated and differentiated groups; significantly more in differentiated | NT |
Huang et al.[6] | Wistar rat (allogeneic) or Lewis (syngeneic) MSCs to Lewis rat MI model | MHCIa upregulated and MHCIb downregulated after in vitro differentiation. MHCII and CD86 co-expressed by dMSCs. Increased susceptibility to cytotoxic lysis | NT | Significantly more undifferentiated MSCs than dMSCs were engrafted at day 7 | Engrafted dMSCs co-expressed MHCI or MHCII with differentiation markers | Allogeneic MSC-treated animals displayed loss of functional benefit over time compared to syngeneic MSC-treated animals | Leukocyte infiltration into allogeneic MSC-treated hearts | Allo-antibodies produced against differentiated but not undifferentiated MSCs |
Dhingra et al.[18] | Wistar MSCs to Lewis rat MI | dMSCs more susceptible to cytotoxic lysis | MSCs lose ability to secrete PGE2 as they differentiate, which results in reduced ability to induce Tregs | MSCs were eliminated by 5Â weeks; some remained engrafted after PGE2 augmentation | NT | Improvement noted, but this was significantly less than if PGE2 was co-administered with allogeneic MSCs | Increased CD8+ T-cell infiltration in dMSC-treated hearts, which could be rescued by PGE2 | Allo-antibodies produced against dMSCs, which could be reduced by PGE2 |
Amado et al.[43] | Allogeneic porcine MSCs to porcine MI | NT | NT | Reported 42.4 ± 15% engraftment at 8 weeks. Labelled engrafted cells co-expressed differentiation markers | NT | Significant improvement after 8 weeks | NT | NT |
Makkar et al.[44] | Allogeneic porcine MSCs to porcine heart 1Â month after MI | NT | NT | Engrafted cells detected 2Â months after injection | NT | No further deterioration in treated group compared to control | NT | NT |
Perin et al.[45] | Allogeneic canine MSCs to canine MI model delivered either intra-coronarily or transendocardially | NT | NT | Engrafted cells detected 14Â days after administration | NT | Transendocardially delivered allo-MSCs provided a functional benefit | NT | NT |
Quevedo et al.[42] | Allogeneic porcine MSCs to porcine MI | NT | NT | Engrafted cells detected at 84Â days co-expressing differentiation markers | NT | Improved cardiac function compared to control group | NT | NT |
Dai et al.[46] | Allogeneic ACI rat MSCs to Fischer rat MI | NT | NT | 7 of 7 hearts at 6Â months showed engrafted MSCs that co-expressed myocardium markers | NT | Improved LVEF at 4Â weeks in allogeneic MSC-treated rats compared to control; effects were lost by 6Â months | NT | NT |