Induced Pluripotent Stem Cells Suppress Cancer Proliferation through Mitochondrial Transfer in a 3D Bioprinting Model
Poster #: 120
Session/Time: A
Author:
Emilee Anne Peterson, BS
Mentor:
Robert Bruno, PhD
Research Type: Basic Science
Abstract
INTRODUCTION:
The regenerating mammary microenvironment has the unique ability to redirect non-mammary and cancer cells to a normal cell fate (1, 2). Our group has shown mitochondrial transfer from mammary epithelial cells to cancer cells contributes to this cancer fate redirection (3). We studied if mitochondrial transfer from induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSC) could redirect cancer cells without the mammary microenvironment, as studies have shown that embryonic stem cells (ESCs) have the extraordinary ability to redirect cancer cells without the mammary niche. The iMSCs transferred their mitochondria, however, it caused increased glycolysis in the cancer cells. This transfer did not suppress tumorigenicity in 3D tumoroid models, contrary to the findings seen with normal mammary epithelial cells (3). Our aim is to investigate if mitochondrial transfer from iPSCs could redirect cancer cells in the absence of the mammary niche.
METHODS:
To visualize mitochondrial transfer, we labeled active mitochondria in iPSCs with MitoTracker live cell stain. We investigated mitochondrial transfer in 2D and 3D cocultures using our novel 3D bioprinting system to print 3D chimeric tumoroid models of mammary cancer cells and iPSCs in collagen hydrogels.
RESULTS:
It was found that iPSCs transferred their mitochondria to mammary cancer cells in 2D and 3D, resulting in decreased growth rates in the cancer cells. The iPSCs did not induce apoptosis or alter the metabolic profile of the cancer cells. Finally, iPSC-derived extracellular vesicles (EVs) were found to transfer mitochondria and similarly decrease cancer growth in 2D and 3D.
CONCLUSION:
Overall, iPSCs have the capability to suppress tumorigenicity in mammary cancer cells through mitochondrial transfer, with a possibility of cancer redirection. Highly concentrated iPSC-derived EV transfer can mimic the anti-proliferative effects of the parent cells in 3D in vitro models, broadening the potential for cell-free approaches in cancer research.
The regenerating mammary microenvironment has the unique ability to redirect non-mammary and cancer cells to a normal cell fate (1, 2). Our group has shown mitochondrial transfer from mammary epithelial cells to cancer cells contributes to this cancer fate redirection (3). We studied if mitochondrial transfer from induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSC) could redirect cancer cells without the mammary microenvironment, as studies have shown that embryonic stem cells (ESCs) have the extraordinary ability to redirect cancer cells without the mammary niche. The iMSCs transferred their mitochondria, however, it caused increased glycolysis in the cancer cells. This transfer did not suppress tumorigenicity in 3D tumoroid models, contrary to the findings seen with normal mammary epithelial cells (3). Our aim is to investigate if mitochondrial transfer from iPSCs could redirect cancer cells in the absence of the mammary niche.
METHODS:
To visualize mitochondrial transfer, we labeled active mitochondria in iPSCs with MitoTracker live cell stain. We investigated mitochondrial transfer in 2D and 3D cocultures using our novel 3D bioprinting system to print 3D chimeric tumoroid models of mammary cancer cells and iPSCs in collagen hydrogels.
RESULTS:
It was found that iPSCs transferred their mitochondria to mammary cancer cells in 2D and 3D, resulting in decreased growth rates in the cancer cells. The iPSCs did not induce apoptosis or alter the metabolic profile of the cancer cells. Finally, iPSC-derived extracellular vesicles (EVs) were found to transfer mitochondria and similarly decrease cancer growth in 2D and 3D.
CONCLUSION:
Overall, iPSCs have the capability to suppress tumorigenicity in mammary cancer cells through mitochondrial transfer, with a possibility of cancer redirection. Highly concentrated iPSC-derived EV transfer can mimic the anti-proliferative effects of the parent cells in 3D in vitro models, broadening the potential for cell-free approaches in cancer research.