Potent Skin Allograft Survival Prolongation Using a Committed Progenitor Fraction of Bone Marrow in Mice

Abstract

Cells enriched for C-kit+lin+ constitute approximately 5% of murine BM cells and are more potent than whole BM at prolonging skin allograft survival in mice treated with ALS and Sir.

Bone Marrow Lin-/Sca-1+/C-Kit+ and Lin-/Sca-1-/C-Kit+ cells Induce Stable Mixed Chimerism and Permanent Skin Graft Acceptance in a Mouse Model

“…The third cell population (G1), lin -/Sca-1 + /c-kit -, prolonged the survival just up to the level observed in the control mice that were only subjected to the induction protocol and not cell transplantation. The costimulatory blockade used in our induction method without bone marrow transplantation has been reported to prolong skin graft survival, which we found in the CP control group as well, but it has not been shown to create tolerance [5]. As we confirmed in our experiment, each graft rejection was preceded by a decrease in chimerism rate, which is consistent with previous studies [5,12].…”

“…To date, diverse cells have been studied. Because mixed chimerism is defined as the coexistence of donor and recipient hematopoietic cells, hematopoietic stem/progenitor cells have become the populations of major interest [4,5]. Finding the appropriate cell population could help to increase the level of mixed chimerism, lower the number of transplanted bone marrow cells required for mixed chimerism induction and promote tolerance to donor antigens.…”

“…Furthermore, mouse embryonic cells, which were shown to induce mixed chimerism and tolerance to cardiac allografts, express these antigens [14]. To date, only c-kit + and lin -/Sca-1 + cells individually were examined in mixed chimerism experiments [5,26]. Taking these facts into consideration, we assessed for the first time the efficacy of lin CB -37d CB -37d The experimental (G1-G3) and control (CP-mice exposed to induction protocol without bone marrow transplantation, CW-mice with skin allografts without any other treatment, CB-mice with syngeneic skin grafts without any other treatment) groups are shown.…”

“…Consequently, the induction protocol, which should be effective but non-toxic to the recipient, is of great importance. Donor cell populations that can help to create stable mixed chimerism with the lowest possible dose of transplanted cells are also under investigation [4,5]. Various cells have been suggested to create tolerance in mixed chimerism studies.…”

“…Because the transplantation of hematopoietic cells has been known to induce tolerance to donor antigens for over half a century [6], bone marrow stem cells have attracted the interest of many scientists. These are cell populations enriched in hematopoietic stem/ progenitor cells: CD34 + cells in humans [4,7,8] and c-kit + cells in mice [5]. Moreover, diverse cell populations have been tested as additions to unfractionated bone marrow to support tolerance induction.…”