Rezai Nana, Corbel Stephane Y, Dabiri Darya, Kerjner Alexandra, Rossi Fabio M V, McManus Bruce M, Podor Thomas J
Department of Pathology and Laboratory Medicine, The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St Paul's Hospital-University of British Columbia, Vancouver, BC, Canada.
Lab Invest. 2005 Aug;85(8):982-91. doi: 10.1038/labinvest.3700302.
Currently, there is intense debate regarding the origin of reparative cells in injured hearts and vasculature. To determine the contribution of recipient bone marrow (BM)-derived cells to the regeneration of cells in the vasculature of transplanted hearts and to examine the effect of immunosuppression on this phenomenon, we evaluated the fate of green fluorescent protein (GFP)-positive recipient BM cells in non-GFP-expressing cardiac allografts. C57BL/6 BM-GFP chimeric recipients underwent cardiac transplantation. Allografts were immunosuppressed with tacrolimus for 14 or 30 days post-transplantation or were saline treated. Hearts were excised and stained with markers for endothelial cells (EC) or smooth muscle cells (SMC). Colocalization with BM-derived recipient cells was evaluated using confocal microscopy with three-dimensional image analysis. Immunosuppression with tacrolimus did not affect the frequency of recipient BM-derived cell chimerism as EC or SMC phenotypes. A higher frequency of EC chimerism was found at 14 days as compared to 30 days post-transplantation in allograft hearts. BM-derived recipient cells are recruited to areas of donor vascular injury with intercalation of recipient EC and SMC in the setting of ongoing alloimmune recognition of the allograft. Our findings confirm that immunosuppression with tacrolimus does not affect the frequency of recipient BM-derived cell repopulation at an early time point 14 days post-transplantation. EC repopulation by BM-derived recipient cells was found to be an early event in transplanted allograft hearts, which decreased in frequency over time.
目前，关于受损心脏和血管中修复性细胞的起源存在激烈争论。为了确定受体骨髓（BM）来源的细胞对移植心脏血管中细胞再生的贡献，并研究免疫抑制对这一现象的影响，我们评估了绿色荧光蛋白（GFP）阳性的受体BM细胞在不表达GFP的心脏同种异体移植物中的命运。C57BL/6 BM-GFP嵌合受体接受了心脏移植。同种异体移植物在移植后用他克莫司免疫抑制14天或30天，或用生理盐水处理。切除心脏并用内皮细胞（EC）或平滑肌细胞（SMC）的标志物进行染色。使用共聚焦显微镜和三维图像分析评估与BM来源的受体细胞的共定位。用他克莫司进行免疫抑制并不影响受体BM来源的细胞嵌合作为EC或SMC表型的频率。与移植后30天相比，同种异体移植心脏在14天时发现EC嵌合的频率更高。在同种异体移植物持续进行同种异体免疫识别的情况下，BM来源的受体细胞被募集到供体血管损伤区域，受体EC和SMC发生嵌入。我们的研究结果证实，移植后14天的早期时间点，用他克莫司进行免疫抑制并不影响受体BM来源的细胞重新填充的频率。发现BM来源的受体细胞对EC的重新填充是移植的同种异体移植心脏中的一个早期事件，其频率随时间下降。
