Table 1 Summary table of differentiated allogeneic MSC in bone 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 |
|---|---|---|---|---|---|---|---|---|
Wang et al.[37] | In vitro assessment of osteogenically differentiated MSCs from swine | No increase in SLAI. Slight increase in SLAII. Osteogenically differentiated MSCs were equivalently immunogenic as undifferentiated MSCs | Osteogenically differentiated and undifferentiated MSCs displayed equivalent immunosuppressive ability | NT | NT | NT | NT | NT |
Liu et al.[7] | Osteogenically differentiated rabbit MSCs; ectopic transplant | Osteogenically differentiated MSCs lacked surface MHCII. No difference in in vitro immunogenicity or susceptibility to cytotoxic lysis | No difference in immunosuppressive ability between differentiated and undifferentiated MSCs | NT | Upregulation of MHCII on implanted dMSCs | Implanted allogeneic dMSCs produced osteonectin and osteopontin in vivo | No increased rejection of allogeneic skin grafts after dMSC treatment | NT |
Le Blanc et al.[38] | In vitro assessment of human dMSCs | No significant increase in in vitro immunogenicity despite increase in HLAI cell surface expression | Osteogenically differentiated MSCs retained their immunosuppressive ability in vitro | NT | NT | NT | NT | NT |
Kang et al.[31] | Allogeneic MSCs in allogeneic bone matrix to radial defect in New Zealand White rabbit | NT | NT | Both autologous and allogeneic MSCs were capable of facilitating bone regeneration | NT | Initial bone quality index equivalent between autologous and allogeneic MSCs, but significantly higher in autologous MSC-treated group after 12Â weeks | No cellular infiltrate observed | NT |
Arinzeh et al.[32] | Scaffold loaded allogeneic MSCs to canine critical sized femoral defect | NT | NT | Implanted allogenic MSC detected up to 16Â weeks | NT | Bone regeneration observed at 16Â weeks | No lymphocytic infiltration observed | No alloantibodies detected |
Kotobuki et al.[34] | Lewis MSCs on hydroxyapatite scaffolds to F344 rats | NT | NT | NT | NT | Immunosuppression was required for in vivo osteogenic differentiation of allogeneic MSCs | Possible infiltration of inflammatory cells | NT |
Chatterjea et al.[35] | Allogeneic MSC-derived osteoprogenitors in ectopic rat model | NT | NT | NT | NT | Allogeneic osteoprogenitors require immunosuppression to form bone | T and B cell infiltration to allogeneic graft. Effects were mediated by immunosuppression | NT |
Ren et al.[36] | MHCI knock-down MSCs in various animal models | NT | NT | NT | NT | MHCI knock-down MSC-treated animals showed better bone regeneration | Higher frequency of circulating activated lymphocytes in animals treated with wild-type MSCs | NT |
Horwitz et al.[30] | OI patients who had previously received bone marrow transplants administered MSCs derived from the same donor | NT | NT | 5 of 6 patients demonstrated MSC engraftment | NT | 5 of 6 patients demonstrated markedly increased growth velocity | Cellular response to viral antigens in some patients | 1 patient produced anti-FBS antibodies |
Le Blanc et al.[29] | Allogeneic foetal liver-derived MSCs to foetus diagnosed with OI | NT | NT | Allogeneic dMSCs detected in bone biopsy at 9Â months (up to 7.4%) | NT | Patient growth could be attributed to allogeneic MSC therapy | No memory response against donor undifferentiated MSCs | Â |