Contreras, Zelenia, 2015-2016

Zelenia Contreras
Zelenia
Contreras

"shRNA Knockdown of METTL3 in Human Mesenchymal Stem Cells (hMSCS) to Prolong Expansion and Regenerative Properties "

Host Mentor: Jan Nolta, Ph.D.
UC Davis Institute for Regenerative Cures

Mesenchymal stem cells (MSCs) are adult stem cells that have significant clinical implications due to their multipotent ability to differentiate into the mesodermal lineage, their involvement in tissue repair, and secretion of cytokines that promote healing. However, it is known that MSCs populate a small fraction of cells in the bone marrow, therefore necessitating in-vitro expansion and pooling different MSCs donor banks for treatment. Unfortunately, challenges arise with expansion of these cells due to the proliferation rate of MSCs decreasing with extended passaging along with the loss of regenerative properties. To overcome these issues, researchers pool multiple donor MSCs however, there is considerable donor-to-donor variability in MSC population in ability to respond to environmental cues, differentiate, and proliferate. The variability of MSCs may decrease the efficacy of these cells in clinical trials. In order to address these issues, this study aims to knockdown (KD) METTL3, a methyltransferase known to be involved in post-transcriptional RNA modification and a regulator of core self-renewal maintenance genes to elucidate the potential of KD METTL3 in MSCs in overcoming in-vitro expansion limits and in reducing the need to pool donor cells.