脂肪基质血管成分的给药可减轻循环死亡后大鼠肾移植中的急性排斥反应。

Administration of adipose stromal vascular fraction attenuates acute rejection in donation after circulatory death rat renal transplantation.

机构信息

Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Center of Renal Transplantation, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Int J Urol. 2022 Mar;29(3):266-275. doi: 10.1111/iju.14757. Epub 2021 Dec 15.

DOI:10.1111/iju.14757

PMID:34908191

Abstract

OBJECTIVE

Stem cell therapy represents a new approach to induce immune tolerance in solid organ transplantation. However, the time-consuming process of stem cell expending limits the range of stem cell treatment. Uncultured adipose stromal vascular fraction is considered an attractive cell source for cell-based therapy. This study aimed to evaluate the effect of stromal vascular fraction on the immune system in donation after circulatory death rat renal transplantation.

METHODS

Stromal vascular fraction cells and splenocytes were co-cultured to evaluate the effect of stromal vascular fraction on splenocyte proliferation and viability. Sprague-Dawley rats were used as donors. and Wistar rats as recipients to establish a donation after a circulatory death rat renal transplantation model. Warm ischemia time was 5 min. Stromal vascular fraction was administered in the rat model following the intra-arterial route. The spleens and grafts of recipients were harvested on days 1, 3 and 7 post-transplantation for assessing acute rejection, infiltration of inflammatory cells, indoleamine 2, 3-dioxygenase expression and T-cell frequency in the spleen.

RESULTS

Stromal vascular fraction could inhibit proliferation and induce apoptosis of splenocytes in vitro (P < 0.05). The administration of stromal vascular fraction could significantly reduce acute rejection and infiltration of CD8 T cells and mononuclear macrophages in grafts, and increase indoleamine 2, 3-dioxygenase expression (P < 0.05). The frequency of CD8 T cells decreased, and the frequency of CD25 Foxp3 regulatory T cells increased in the spleen of the acute rejection + stromal vascular fraction group on day 7 post-transplantation (P < 0.05).

CONCLUSION

Administration of the adipose stromal vascular fraction could attenuate acute rejection in donation after circulatory death renal transplantation by increasing the ratio of regulatory T cells and enhancing indoleamine 2, 3-dioxygenase expression.

摘要

目的

干细胞治疗代表了一种诱导实体器官移植中免疫耐受的新方法。然而，干细胞扩增的耗时过程限制了干细胞治疗的范围。未培养的脂肪基质血管部分被认为是细胞治疗有吸引力的细胞来源。本研究旨在评估基质血管部分对死后循环大鼠肾移植中免疫系统的影响。

方法

将基质血管部分细胞和脾细胞共培养，以评估基质血管部分对脾细胞增殖和活力的影响。使用 Sprague-Dawley 大鼠作为供体，Wistar 大鼠作为受体建立死后循环大鼠肾移植模型。热缺血时间为 5 分钟。在动脉内途径给予基质血管部分。在移植后第 1、3 和 7 天收获受体的脾脏和移植物，以评估急性排斥反应、炎性细胞浸润、脾内吲哚胺 2,3-双加氧酶表达和 T 细胞频率。

结果

基质血管部分可在体外抑制脾细胞增殖并诱导其凋亡（P<0.05）。给予基质血管部分可显著减少移植物中的急性排斥反应和 CD8 T 细胞和单核巨噬细胞浸润，并增加吲哚胺 2,3-双加氧酶表达（P<0.05）。在移植后第 7 天，急性排斥反应+基质血管部分组脾脏中 CD8 T 细胞的频率降低，CD25 Foxp3 调节性 T 细胞的频率增加（P<0.05）。