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

Abstract

Background Artificial 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 °C and then co-incubated at 37 °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. Results Using 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. Conclusion Our 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. Electronic supplementary material The online version of this article (10.1186/s12896-019-0534-6) contains supplementary material, which is available to authorized users.

Bases for Treating Skin Aging With Artificial Mitochondrial Transfer/Transplant (AMT/T)

“…Cells naturally exchange mitochondria as repairing mechanisms. This process has inspired the development of new therapies, some of which have been developed by several researchers and are currently used in vitro , in vivo , and in clinical applications ( Emani et al, 2017 ; Gollihue et al, 2018 ; Cabrera et al, 2019 ).…”

“…The use of mitochondria as a therapeutic agent by artificial mitochondria transfer/transplant (AMT/T) is gaining more evidence of its regenerative effects from in vitro to in vivo approaches, treating ischemic diseases in the majority of cases ( Caicedo et al, 2015 , 2017 ; Emani et al, 2017 ; Cabrera et al, 2019 ). This process aims to use mitochondria to repair damaged cells and tissue, alone or as a complement to current standards of therapy.…”

“…This process aims to use mitochondria to repair damaged cells and tissue, alone or as a complement to current standards of therapy. AMT/T could be applied to enhance proliferation, migration, tissue regeneration and stress resistance of recipient cells ( Caicedo et al, 2015 ; Lin et al, 2015 ; Emani et al, 2017 ; Cabrera et al, 2019 ). In vitro , Clark and Shay (1982) were the first to show that AMT/T is able to effectively transfer antibiotic resistance coded by the mtDNA to sensitive mammalian cells when they received exogenous mitochondria ( King and Attardi, 1988 ).…”

“…Mitochondrial dysfunction increases as age progresses. This organelle accumulates damage with age and through the constant exposure to external factors, like ultraviolet radiation (UVR), which harms its function and genetic patrimony ( Naidoo et al, 2018 ; Cabrera et al, 2019 ). The presence of dysfunctional mitochondria has been associated with neurological and degenerative disorders, obesity, type 2 diabetes, and cancer ( Angelova and Abramov, 2018 ; Porporato et al, 2018 ; Cantó, 2019 ).…”

“…For example, MitoCeption, one of many AMT/T techniques, induces cell proliferation, migration, and increased respiratory ATP production, processes needed to repair the damage in aged skin ( Caicedo et al, 2015 ). PAMM MitoCeption (Primary Allogeneic Mitochondria Mix Transfer by MitoCeption) repaired UVR damaged cells by recovering the loss of metabolic activity, mitochondrial mass, mtDNA sequence stability in addition to decreasing p53 expression ( Cabrera et al, 2019 ). Published data provided evidence that syngeneic or allogeneic AMT/T transfer of mitochondria was not immunogenic, and additionally that AMT/T to proinflammatory cells, such as TH17, induced cell conversion to Tregs and promoted immune regulation ( Luz-Crawford et al, 2019 ; Ramirez-Barbieri et al, 2019 ).…”