Can stem cells be used to transplant healthy mitochondrira?

This proposal seeks to explore the therapeutic potential of hematopoietic stem cell transplantation (HSCT) in a mouse model of FA and identify the mechanisms of metabolic correction by HSCT. For many years, HSCT has been used to treat severe neurodegenerative diseases in children. Recent studies in mice have shown that HSCT may also be beneficial for treating FA. The idea is that stem cells can become cells that act like microglia or macrophages (types of immune cells) in the body, which can help correct metabolic issues in cells affected by the disease by transferring healthy mitochondria. However, this idea is still controversial and needs more testing. The goal of this project is to test if HSCT can help treat FA using a mouse model of the disease and to investigate the role of the chemotherapy used before the transplant. Dr. Cho has shown that FA mice might require less chemotherapy before the transplant compared to mice with normal levels of frataxin, that cells with low frataxin expression have better mitochondrial transfer, and that low-dose chemotherapy before HSCT can improve symptoms in FA mice. The plan is to test HSCT’s potential effectiveness by looking at how it affects cells and molecules in the human FXN transgenic mouse model with more than 800 GAA trinucleotide repeats. Dr Cho will also study how cells transfer mitochondria in vitro and in vivo and identify potential mechanisms using unbiased approaches like single cell-RNA sequencing and proteomics. If successful, this study will provide more evidence to support the use of HSCT to treat FA and may offer new insights into how cells can correct metabolic issues by transferring mitochondria.