Syngeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide to induce immune tolerance of allogenic skin graft survival in rat.
5 affiliations
- 1Chair and Department of Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland. [email protected].
- 2Department of Pathology, Medical University of Warsaw, Warsaw, Poland.
- 3Chair and Department of Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
- 4Central Laboratory of Experimental Animals, Medical University of Warsaw, Warsaw, Poland.
- 5Institute of Medical Sciences, University of Zielona Góra, Zielona Góra, Poland.
Abstract
In haploidentical hematopoietic stem cell transplantation (HSCT), the addition of post-transplantation cyclophosphamide (Cy) can help to induce immunotolerance between the donor and haploidentical immune system, preventing graft-versus-host disease between the haploidentical immune system and organs/ tissues of the recipient. We hypothesized that the situation could be reversed and replicated during the transplantation of allogenic tissue and syngeneic (autologous model) HSCT with post-HSCT Cy. We hypothesized that conditioning (pre-HSCT Cy) causes immunoablation of the recipient, and post-HSCT Cy deletes allo-reactive clones from transplanted HSC thus enabling immunotolerance to simultaneously transplanted tissue (organ). To test this hypothesis, we developed a model of autologous HSCT (syngeneic HSCT) with simultaneous transplantation of allogenic tissue in rat. The study rats received: first immunoablation, then allogenic skin graft and syngeneic HSCT, and later post-transplantation Cy. The administration of Cy before and after syngeneic HSCT with simultaneous transplantation of skin graft prolonged skin graft survival from 3 to 12 days and changed the pattern of rejection. The addition of Cy post-HSCT resulted in a statistically significant increase in TNFα secretion before rejection compared to acute rejection without Cy post-HSCT. The sole administration of Cy before and after syngeneic HSCT with simultaneous organ transplantation is not sufficient to achieve full tolerance to allogenic tissue. However, with changes to conditioning or additional immunosuppression, this goal could be achieved.
Related
- T-cell polyfunctionality reconstitution after modified anti-thymocyte globulin plus post-transplant cyclophosphamide in allogeneic hematopoietic stem cell transplantation
- Hematopoietic cell transplantation using treosulfan-based conditioning for IL-10 receptor deficiency
- Longitudinal plasma proteome profiling after allogeneic hematopoietic stem cell transplantation: heterogeneous development and associations with acute GvHD
- Recipient-driven metabolic and epigenetic remodeling of donor hematopoietic cells after transplantation in Fanconi Anemia.
- BCL10 deficiency: Long-term immune reconstitution following hematopoietic stem cell transplantation.
BibTeX
@article{kasarello2026syngeneic,
title = {{Syngeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide to induce immune tolerance of allogenic skin graft survival in rat.}},
author = {Kaja Kasarełło and Renata Podkowińska-Polak and Piotr Olejnik and Jacek Dziedziak and Robert Wrzesień and Agnieszka Cudnoch-Jędrzejewska and Emilian Snarski},
journal = {Immunologic research},
year = {2026},
month = oct,
doi = {10.1007/s12026-026-09862-3},
url = {https://europepmc.org/article/MED/42911302},
note = {CC BY},
}
RIS
TY - JOUR
TI - Syngeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide to induce immune tolerance of allogenic skin graft survival in rat.
AU - Kaja Kasarełło
AU - Renata Podkowińska-Polak
AU - Piotr Olejnik
AU - Jacek Dziedziak
AU - Robert Wrzesień
AU - Agnieszka Cudnoch-Jędrzejewska
AU - Emilian Snarski
PY - 2026
DA - 2026/10/22
JO - Immunologic research
DO - 10.1007/s12026-026-09862-3
UR - https://europepmc.org/article/MED/42911302
AB - In haploidentical hematopoietic stem cell transplantation (HSCT), the addition of post-transplantation cyclophosphamide (Cy) can help to induce immunotolerance between the donor and haploidentical immune system, preventing graft-versus-host disease between the haploidentical immune system and organs/ tissues of the recipient. We hypothesized that the situation could be reversed and replicated during the transplantation of allogenic tissue and syngeneic (autologous model) HSCT with post-HSCT Cy. We hypothesized that conditioning (pre-HSCT Cy) causes immunoablation of the recipient, and post-HSCT Cy deletes allo-reactive clones from transplanted HSC thus enabling immunotolerance to simultaneously transplanted tissue (organ). To test this hypothesis, we developed a model of autologous HSCT (syngeneic HSCT) with simultaneous transplantation of allogenic tissue in rat. The study rats received: first immunoablation, then allogenic skin graft and syngeneic HSCT, and later post-transplantation Cy. The administration of Cy before and after syngeneic HSCT with simultaneous transplantation of skin graft prolonged skin graft survival from 3 to 12 days and changed the pattern of rejection. The addition of Cy post-HSCT resulted in a statistically significant increase in TNFα secretion before rejection compared to acute rejection without Cy post-HSCT. The sole administration of Cy before and after syngeneic HSCT with simultaneous organ transplantation is not sufficient to achieve full tolerance to allogenic tissue. However, with changes to conditioning or additional immunosuppression, this goal could be achieved.
SN - 0257-277X
SN - 1559-0755
ER -