Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model.
Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model.
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脂肪源性细胞疗法可延长同种异体后肢移植模型中的移植物存活率
DOI：
10.1186/s13287-021-02162-7
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发表时间：
2021-01-29
影响因子：
7.5
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Chen J;Wang Y;Hu H;Xiong Y;Wang S;Yang J
血管化复合同种异体移植（VCA）后的长期生存常受到全身排斥反应和免疫抑制剂不良反应的限制。基质血管部分（SVF）可以扩增以产生脂肪源性干细胞（ADSC），其代表内皮细胞、前脂肪细胞、免疫细胞和ADSC的组合。已证明ADSC具有一致可靠的临床结果。然而，文献是稀缺的VCA SVF。本研究旨在确定的影响，离体移植物预处理结合SVF细胞的能力，以促进复合组织同种异体移植immunotolerance.MethodsA大鼠后肢同种异体移植模型的影响进行了调查，离体预处理的SVF和ADSC对VCA的生存。将血管内无细胞盐水、ADSC或SVF注入具有免疫抑制剂的模型中。记录组织病理学检查和移植物未出现排斥反应症状的持续时间。外周血T淋巴细胞和T淋巴细胞计数用流式细胞术定量，而同种异体组织表达的CD 31用免疫组化染色（IHC）定量。ELISA被用来检测血管内皮生长因子（VEGF）-A，以及抗-和促炎cytokines.ResultsWe证明，体外治疗的同种异体移植物与SVF或ADSC延长同种异体移植物的存活率相比，中对照组。也有免疫调节细胞因子和VEGF-A和CD 31的表达水平增加，以及减少浸润和T淋巴细胞增殖沿着与提高Treg expressions.ConclusionThese研究表明，脂肪衍生的细胞疗法延长移植物存活在同种异体后肢移植模型，并有可能建立免疫耐受。
BackgroundThe 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.MethodsA 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.ResultsWe 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.ConclusionThese studies demonstrated that adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model and have the potential to establish immunotolerance.
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