Intercellular Mitochondrial Transfer Using 3D Bioprinting

Intercellular Mitochondrial Transfer Using 3D Bioprinting

College

College of Health Sciences

Department

Medical Diagnostic & Translational Sciences

Graduate Level

Doctoral

Graduate Program/Concentration

Biomedical Sciences

Publication Date

4-2022

DOI

10.25883/mbdn-s255

Abstract

Mitochondria are one of the most complex and vital organelles in eukaryotic cells. In recent years, it has been shown that through intercellular mitochondrial transfer, this important organelle provides a critical role in tissue homeostasis, damaged tissue repair, and tumor progression under physiological conditions. However, the mechanism of mitochondrial transfer and its effect on various cellular microenvironments has not yet been defined. Understanding the metabolic effects of mitochondrial transfer between cells and exploring the signaling leading to the intercellular mechanisms could provide advancements in both translational medicine and cell therapy for cancer progression and age-related diseases. Our group has studied the ability of the normal mammary microenvironment to redirect cancer cells to a normal mammary epithelial cell fate both in vivo and in vitro using our 3D bioprinting system. Therefore, we sought to determine if mitochondrial transfer may play a role in mammary epithelium induced redirection of cancer cells. We used MCF-7 breast cancer cells and MCF-12a epithelial breast cells for experimentation. Using a fluorescent GFP-MITO lentivirus, we were able to mark mitochondrial protein in the MCF-12a epithelial cells to track mitochondrial transfer activity. The MCF-7 cells were labeled red to distinguish the two cell types. The cells were then co-cultured in 2D tissue flasks and printed into hydrogels using the 3D bioprinter. Using fluorescent microscopy, mitochondrial protein was observed traveling from epithelial to mammary cancer cells. We hypothesize this is done for cancer cells to stabilize mitochondria and improve metabolic function and ATP production. Further research to establish mitochondrial transfer, its mechanism(s), and molecular effects could lead insight into how this cellular communication rescues and normalizes metabolic factors of the mammary and stem cell microenvironment leading to potential fate redirection and cellular revitalization.

Keywords

Bioprinting, Mitochondria, Mitochondrial transfer, Cancer, 3D Culture, Microenvironment

Disciplines

Medical Biotechnology | Medical Cell Biology | Medical Molecular Biology | Other Medical Sciences

Intercellular Mitochondrial Transfer Using 3D Bioprinting


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