Chen Jingting, Wang Yinmin, Hu Haoyue, Xiong Yao, Wang Shoubao, Yang Jun
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Plastic and Reconstructive Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Stem Cell Res Ther. 2021 Jan 29;12(1):94. doi: 10.1186/s13287-021-02162-7.
The long-term survival after vascularized composite allotransplantation (VCA) is often limited by systemic rejection as well as the adverse effects of immunosuppressants. The stromal vascular fraction (SVF) can be expanded to produce adipose-derived stem cells (ADSC) which represents a combination of endothelial cells, preadipocytes, immune cells, and ADSC. It has been demonstrated that ADSC possess consistently reliable clinical results. However, literature is scarce regarding SVF in VCA. This study seeks to determine the impact of ex vivo allograft pretreatment in combination with SVF cells in the ability to promote composite tissue allotransplantation immunotolerance.
A rat hind limb allotransplant model was used to investigate the influence of ex vivo pretreatment of SVF and ADSC on VCA survival. Intravascular cell-free saline, ADSC, or SVF was infused into the models with immunosuppressants. The histopathological examination and duration that the allografts went without displaying symptoms of rejection was documented. Peripheral T lymphocytes and Tregs were quantified with flow cytometry while allotissue expressions of CD31 were quantified with immunohistochemical staining (IHC). ELISA was used to detect vascular endothelial growth factor (VEGF)-A as well as anti- and pro-inflammatory cytokines.
We demonstrated that ex vivo treatment of allografts with SVF or ADSC prolonged allograft survival in contrast to medium control cohorts. There were also enhanced levels of immunomodulatory cytokines and increased VEGF-A and CD31 expression as well as reduced infiltration and proliferation of T lymphocytes along with raised Treg expressions.
These studies demonstrated that adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model and have the potential to establish immunotolerance.
血管化复合组织异体移植（VCA）后的长期存活常受全身排斥反应以及免疫抑制剂不良反应的限制。基质血管成分（SVF）可经扩增产生脂肪来源干细胞（ADSC），后者是内皮细胞、前脂肪细胞、免疫细胞和ADSC的组合。已证实ADSC具有始终可靠的临床效果。然而，关于VCA中SVF的文献较少。本研究旨在确定异体移植物体外预处理联合SVF细胞对促进复合组织异体移植免疫耐受能力的影响。
采用大鼠后肢异体移植模型研究SVF和ADSC体外预处理对VCA存活的影响。将无细胞生理盐水、ADSC或SVF与免疫抑制剂注入模型。记录异体移植物无排斥症状出现的组织病理学检查结果及持续时间。用流式细胞术定量外周血T淋巴细胞和调节性T细胞（Tregs），用免疫组织化学染色（IHC）定量异体组织中CD31的表达。采用酶联免疫吸附测定（ELISA）检测血管内皮生长因子（VEGF）-A以及抗炎和促炎细胞因子。
我们证明，与培养基对照组相比，用SVF或ADSC对异体移植物进行体外处理可延长异体移植物存活时间。免疫调节细胞因子水平也有所提高，VEGF-A和CD31表达增加，T淋巴细胞浸润和增殖减少，Tregs表达升高。
这些研究表明，脂肪来源的细胞疗法可延长同种异体后肢移植模型中的移植物存活时间，并具有建立免疫耐受的潜力。
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