Primary allogeneic mitochondrial mix (PAMM) transfer/transplant by MitoCeption to address damage in PBMCs caused by ultraviolet radiation

Primary allogeneic mitochondrial mix (PAMM) transfer/transplant by MitoCeption to address damage in PBMCs caused by ultraviolet radiation
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DOI:
10.1186/s12896-019-0534-6
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发表时间:
2019-06-28
期刊:
影响因子:
3.5
通讯作者:
Caicedo, Andres
Caicedo, Andres
中科院分区:
工程技术3区
文献类型:
--
作者:
Cabrera, Francisco;Ortega, Mayra;Caicedo, Andres

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研究背景人工线粒体转移或移植(AMT/T)可用于减轻损伤细胞的应激和活力丧失。在MitoCeption(一种AMT/T)中,将分离的线粒体和受体细胞一起在4 ° C下离心,然后在正常培养条件下在37 ° C下共孵育,诱导转移。紫外线辐射(UVR)可以影响线粒体和其他细胞结构,导致组织应激,衰老和免疫抑制。AMT/T可修复UVR对细胞和线粒体的损伤。我们研究了如果从不同的捐助者(初级同种异体线粒体混合物,PAMM)的线粒体混合物可以修复紫外线辐射损伤和促进细胞survival.ResultsUsing一个简化的适应的MitoCeption协议,我们使用外周血单核细胞(PBMC)作为受体细胞模型的PAMM,以确定如果这个协议可以修复紫外线辐射损伤。我们的研究结果表明,当PBMCs暴露于紫外线辐射,有一个在代谢活动,线粒体质量和mtDNA序列的稳定性下降,以及增加p53的表达和死亡细胞的百分比。当PAMM MitoCeption被用于UVR损伤的细胞,它成功地将线粒体从不同的捐助者不同的PBMC群体和修复观察到的UVR damage.ConclusionOur结果代表了MitoCeption和其他AMT/T的应用程序的进步。我们表明,PBMC可以用作线粒体的PAMM来源。我们还表明,这些线粒体可以从不同的捐助者(PAMM)的混合转移到紫外线损伤,非贴壁原代细胞。此外,我们缩短了MitoCeption方案的持续时间。
BackgroundArtificial Mitochondrial Transfer or Transplant (AMT/T) can be used to reduce the stress and loss of viability of damaged cells. In MitoCeption, a type of AMT/T, the isolated mitochondria and recipient cells are centrifuged together at 4 degrees C and then co-incubated at 37 degrees C in normal culture conditions, inducing the transfer. Ultraviolet radiation (UVR) can affect mitochondria and other cell structures, resulting in tissue stress, aging, and immunosuppression. AMT/T could be used to repair UVR cellular and mitochondrial damage. We studied if a mitochondrial mix from different donors (Primary Allogeneic Mitochondrial Mix, PAMM) can repair UVR damage and promote cell survival.ResultsUsing a simplified adaption of the MitoCeption protocol, we used peripheral blood mononuclear cells (PBMCs) as the recipient cell model of the PAMM in order to determine if this protocol could repair UVR damage. Our results showed that when PBMCs are exposed to UVR, there is a decrease in metabolic activity, mitochondrial mass, and mtDNA sequence stability as well as an increase in p53 expression and the percentage of dead cells. When PAMM MitoCeption was used on UVR-damaged cells, it successfully transferred mitochondria from different donors to distinct PBMCs populations and repaired the observed UVR damage.ConclusionOur results represent an advancement in the applications of MitoCeption and other AMT/T. We showed that PBMCs could be used as a PAMM source of mitochondria. We also showed that these mitochondria can be transferred in a mix from different donors (PAMM) to UVR-damaged, non-adherent primary cells. Additionally, we decreased the duration of the MitoCeption protocol.