Autologous C-kit+ cells robustly prolong cardiac allografts. As C-kit+ cells can transdifferentiate to hematopoietic cells as well as non-hematopoietic cells, we aimed to clarify the class(es) of C-kit-derived cell(s) required for cardiac allograft prolongation. Autologous C-kit+ cells were administered post-cardiac transplantation and allografts were evaluated for C-kit+ inoculum-derived cells. Results suggested that alloimmunity was a major signal for trafficking of C-kit-derived cells to the allograft and demonstrated that C-kit+ inoculum-derived cells expressed CD11b early after transfer. Allograft survival studies with CD11b-DTR C-kit+ cells demonstrated a requirement for C-kit+-derived CD11b+ cells. Co-therapy studies demonstrated near complete abrogation of acute rejection with concomitant CTLA4-Ig therapy and no loss of prolongation in combination with Cyclosporine A. These results strongly implicate a C-kit-derived myeloid population as critical for allograft preservation and demonstrate the potential therapeutic application of autologous C-kit+ progenitor cells as calcineurin inhibitor-sparing agents and possibly as co-therapeutics for durable graft survival.

中文翻译：

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C-kit衍生的CD11b +细胞对于自体C-kit +祖细胞对心脏同种异体移植的延长至关重要。

自体C-kit +细胞可强有力地延长心脏同种异体移植的时间。由于C-kit +细胞可以分化为造血细胞和非造血细胞，因此我们旨在阐明心脏同种异体移植所需的C-kit衍生细胞的类型。心脏移植后施用自体C-kit +细胞，并评估同种异体移植物中C-kit +接种物来源的细胞。结果表明，同种免疫是将C-kit来源的细胞运输到同种异体移植的主要信号，并证明C-kit +接种物的细胞在转移后早期表达CD11b。用CD11b-DTR C-kit +细胞进行的同种异体移植存活研究表明，需要C-kit +衍生的CD11b +细胞。