The Positive Impact of Donor Bone Marrow Cells Transplantation into Immunoprivileged Compartments on the Survival of Vascularized Skin Allografts

Arkadiusz Jundziłł,Aleksandra Klimczak,Grzegorz Brzezicki,Maria Siemionow,Erhan Sonmez

doi:10.1007/s00005-021-00631-8

Abstract

Using the vascularized skin allograft (VSA) model, we compared the tolerogenic effects of different allogeneic bone marrow transplantation (BMT) delivery routes into immunoprivileged compartments under a 7-day protocol immunosuppressive therapy. Twenty-eight fully MHC mismatched VSA transplants were performed between ACI (RT1a) donors and Lewis (RT11) recipients in four groups of seven animals each, under a 7-day protocol of alfa/beta TCRmAb/CsA (alpha/beta-TCR monoclonal antibodies/Cyclosporine A therapy). Donor bone marrow cells (BMC) (100 × 106 cells) were injected into three different immunoprivileged compartments: Group 1: Control, without cellular supportive therapy, Group 2: Intracapsular BMT, Group 3: Intragonadal BMT, Group 4: Intrathecal BMT. In Group 2, BMC were transplanted under the kidney capsule. In Group 3, BMC were transplanted into the right testis between tunica albuginea and seminiferous tubules, and in Group 4, cells were injected intrathecally. The assessment included: skin evaluation for signs and grade of rejection and immunohistochemistry for donor cells engraftment into host lymphoid compartments. Donor-specific chimerism for MHC class I (RT1a) antigens and the presence of CD4+/CD25+ T cells were assessed in the peripheral blood of recipients. The most extended allograft survival, 50–78 days, was observed in Group 4 after intrathecal BMT. The T cells CD4+/CD25+ in the peripheral blood were higher after intrathecal BMC injection than other experimental groups at each post-transplant time point. Transplantation of BMC into immunoprivileged compartments delayed rejection of fully mismatched VSA and induction of robust, donor-specific chimerism.

Highlights

Vascularized composite allografts (VCA) represent a robust model for restoration for significant skin defects (Petit et al 2003)
Allogeneic bone marrow cell (BMC) transplantation is a well-known option for the induction of donor-specific chimerism and prevention of allograft rejection in the experimental models (Asari et al 2011; Leonard et al 2013b; Safinia et al 2013; Siemionow and Nasir 2008)
Our study indicated the importance of different chimeric cell populations playing the role in allograft survival when compared with total chimerism levels below 10%, which is less meaningful

Summary

Introduction

Vascularized composite allografts (VCA) represent a robust model for restoration for significant skin defects (Petit et al 2003). Allogeneic bone marrow cell (BMC) transplantation is a well-known option for the induction of donor-specific chimerism and prevention of allograft rejection in the experimental models (Asari et al 2011; Leonard et al 2013b; Safinia et al 2013; Siemionow and Nasir 2008). The effects of cell-based therapies the following transplantation into immunoprivileged compartments has not been yet well-established as a promising new approach for tolerance induction strategy. There is limited number of studies in the literature on the impact of BMC transplantation into the immunoprivileged regions and its relation with the allograft survival or rejection. We introduced our well-established VCA transplant model to investigate a new tolerogenic approach of different routes of bone marrow transplantation (BMT) into immunoprivileged compartments of vascular skin allograft recipients

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Discussion

Conclusion