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

BMC Biotechnol. 2019 Jun 28;19(1):42. doi: 10.1186/s12896-019-0534-6.

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.

Keywords: Artificial mitochondria transfer / transplant (AMTT); Cell repair; Cellular damage; MitoCeption; Mitochondria; Primary allogeneic mitochondrial mix (PAMM); Primary immune cells; Ultraviolet radiation (UVR); p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Survival / genetics
  • Cells, Cultured
  • DNA Damage*
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Female
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / radiation effects
  • Male
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / transplantation*
  • Reactive Oxygen Species / metabolism
  • Transplantation, Homologous / methods
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ultraviolet Rays*

Substances

  • DNA, Mitochondrial
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53