Poster #: 58A
Session/Time: A
Author:
Emilee Peterson, BS
Mentor:
Patrick Sachs, PhD
Research Type: Basic Science
Abstract
The regenerating mammary microenvironment has the unique ability to redirect non-mammary and cancer cells to a normal cell fate (1, 2). These redirected non-mammary cell types displayed normal mammary epithelial characteristics and contributed to the regeneration of a functional mammary gland epithelial tree. Our group has recently shown that mitochondrial transfer from mammary epithelial cells contributes to the microenvironmental redirection of breast cancer cells (3). We hypothesized that mitochondrial transfer from other cell types could contribute to cell fate redirection, as studies have shown that embryonic stem cells (ESCs) can redirect cancer cells and suppress tumorigenic phenotypes without the mammary niche present (4). Previously in our laboratory, breast adipose-derived stem cells (bASCs) were isolated from mammary fat tissue and reprogrammed into induced pluripotent stem cells (iPSCs), an embryonic-like stem cell. Our aim is to investigate if the intercellular transfer of mitochondria from iPSCs can redirect cancer cells through direct contact and extracellular vesicles (EVs). We studied mitochondrial transfer in 2D and 3D cocultures using our novel 3D bioprinting system to generate 3D chimeric tumoroid models of mammary cancer cells and iPSCs in collagen hydrogels. iPSC-derived EVs were isolated through differential centrifugation and microfiltration, then transferred to the 3D tumoroid models. The iPSCs transferred their mitochondria to mammary cancer cells in 2D and 3D, and coculture experiments resulted in decreased cancer growth rates. The iPSCs did not induce apoptosis or alter the metabolic profile of the cancer cells. Similarly, iPSC-derived EVs transferred mitochondria and decreased tumoroid growth in 3D. iPSCs have the capability to suppress tumorigenicity in mammary cancer cells, with a possibility of cancer redirection. Concentrated iPSC-derived EVs can mimic the anti-proliferative effects of the parent cells in 3D in vitro models, expanding the potential for cell-free approaches in cancer research.