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

被引:26
作者
Cabrera, Francisco [1 ,5 ,9 ,10 ]
Ortega, Mayra [2 ,9 ,10 ]
Velarde, Francesca [9 ,10 ]
Parra, Eliseo [6 ,7 ,8 ]
Gallardo, Stephany [2 ]
Barba, Diego [3 ]
Soto, Lina [3 ]
Pena, Gabriela [3 ]
Alberto Pedroza, Luis [3 ,4 ]
Jorgensen, Christian [5 ,10 ]
Khoury, Maroun [6 ,7 ,8 ,10 ]
Caicedo, Andres [3 ,9 ,10 ,11 ]
机构
[1] Univ San Francisco Quito, Escuela Med Vet, Colegio Ciencias Salud, Quito 1712841, Ecuador
[2] Univ San Francisco Quito, Escuela Biotecnol, Colegio Ciencias Biol & Ambientales, Quito 1712841, Ecuador
[3] Univ San Francisco Quito, Escuela Med, Colegio Ciencias Salud, Quito 1712841, Ecuador
[4] Baylor Coll Med, Dept Pediat, Sect Immunol Allergy & Rheumatol, Houston, TX 77030 USA
[5] Univ Montpellier, IRMB CHU St Eloi, 80 Rue Augustin Fliche, F-34295 Montpellier 5, France
[6] Univ Los Andes, Lab Nanoregenerat Med, Fac Med, Santiago, Chile
[7] Chilean Consortium Regenerat Med, Consorcio Regenero, Santiago, Chile
[8] Cells Cells, Santiago, Chile
[9] Univ San Francisco Quito, Inst Invest Biomed, Quito 1712841, Ecuador
[10] Mito Act Res Consortium, Quito, Ecuador
[11] Univ San Francisco Quito, SIME, Sistemas Med, Quito 1712841, Ecuador
关键词
Mitochondria; MitoCeption; Artificial mitochondria transfer; transplant (AMTT); Primary allogeneic mitochondrial mix (PAMM); Ultraviolet radiation (UVR); Cellular damage; p53; Primary immune cells; Cell repair; CAR-T CELLS; TUNNELING NANOTUBES; IN-VITRO; DNA; TRANSPLANTATION; TRANSFORMATION; BIOMARKER; THERAPY; ASSAYS;
D O I
10.1186/s12896-019-0534-6
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
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页数:14
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