About this Research Topic
The well-known side effects of long-term immunosuppressive treatment (IST) after solid organ transplantation (SOT) represent a substantial burden of morbidity and lead to increased mortality of transplanted patients with respect to the general population. Operational tolerance through donor hematopoietic chimerism in SOT recipients has been reported to be possible, with long-term success even in the presence of transient or mixed chimerism. Favorable results have been mainly obtained in HLA-identical or haploidentical transplants whereas mixed chimerism (MC) is rarely sustained in an HLA-disparate setting, as is the case of most SOTs either from living or deceased donors. The main hurdles for a wide use of MC induction protocols are represented by the HLA disparity between the recipient and the donor, preventing the realization of a sustained MC due to difficulties in obtaining a specific tolerance, at least for now.
The aim of this Research Topic is to resume the most relevant scientific evidence about the MC approach in SOT, to update the state-of-art and to support scientific and clinical progress in this field by consolidating the basis for future biological and clinical studies. Different levels will be considered, ex vivo, in vitro, pre-clinical and clinical data from the literature.
In particular, the obstacles preventing success in the HLA-disparate setting will be pointed-out and discussed; this will enhance discussion about potential progress in the clinical field. Finally, the remarkable improvements in the field of HSCT during recent years have allowed the realization of HLA-mismatched HSCTs, as cord blood or haploidentical transplants. These two elements suggest that HLA disparity between the recipient and the donor no longer represents an insurmountable obstacle in transplantation, but it might be overcome by the use of appropriate immunosuppressive drugs (and/or cellular therapies) and protocols. For this reason, here a multidisciplinary approach is needed to share the most updated knowledge and build up a critical mass of expertise.
We welcome the submissions of Original Research, Review, Mini-Review and Case Report (this last if they represent proof-of-concept and are accompanied by a related review of the literature) articles focusing on, but not limited to, the following points:
• timing and dose of hematopoietic stem cell infusion and/or cell therapy with respect to the transplant
• source and composition of stem cell product
• conditioning regimen and IST protocol
• modulation of IST according to immunological disparities (HLA, eplets) or chimerism results after the combined transplant
• duration of chimerism (i.e., transient, stable mixed) and graft survival.
The aim of this Research Topic is to resume the most relevant scientific evidence about the MC approach in SOT, to update the state-of-art and to support scientific and clinical progress in this field by consolidating the basis for future biological and clinical studies. Different levels will be considered, ex vivo, in vitro, pre-clinical and clinical data from the literature.
In particular, the obstacles preventing success in the HLA-disparate setting will be pointed-out and discussed; this will enhance discussion about potential progress in the clinical field. Finally, the remarkable improvements in the field of HSCT during recent years have allowed the realization of HLA-mismatched HSCTs, as cord blood or haploidentical transplants. These two elements suggest that HLA disparity between the recipient and the donor no longer represents an insurmountable obstacle in transplantation, but it might be overcome by the use of appropriate immunosuppressive drugs (and/or cellular therapies) and protocols. For this reason, here a multidisciplinary approach is needed to share the most updated knowledge and build up a critical mass of expertise.
We welcome the submissions of Original Research, Review, Mini-Review and Case Report (this last if they represent proof-of-concept and are accompanied by a related review of the literature) articles focusing on, but not limited to, the following points:
• timing and dose of hematopoietic stem cell infusion and/or cell therapy with respect to the transplant
• source and composition of stem cell product
• conditioning regimen and IST protocol
• modulation of IST according to immunological disparities (HLA, eplets) or chimerism results after the combined transplant
• duration of chimerism (i.e., transient, stable mixed) and graft survival.
Keywords: Immune tolerance, transplantation, hematopoietic chimerism, HLA, immunosuppressive treatment
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