Medical Research

Sanford Burnham Prebys Medical Discovery Institute

Duc Dong, Clyde Campbell, Joseph Lancman, Sean Zeng
La Jolla
$1,000,000
June 2017

The prevailing strategy for regenerative medicine is to transplant into patients, replacement cells that have been derived outside the body (in vitro), from pluripotent stem cells. However low survival and functional integration of these cultured cells, as well as the inherent risks associated with the process of transplantation and the use of differentiated stem cells which may have acquired tumorigenic defects, remain formidable obstacles for this approach to be considered effective and safe.  To bypass these obstacles, Sanford Burnham Prebys investigators plan to generate replacement cells by directly converting any cell of choice, while they remain in the body (in vivo).  To do this, the investigators must push the boundaries of induced in vivo lineage conversion, challenging the dogma that cells are lineage restricted in their native microenvironment.  Leveraging zebrafish genetics, they have developed a novel in vivo vertebrate platform to rapidly identify and optimize transcription factors that can induce differentiated cells to change into lineages of interest.  Using this in vivo platform, the researchers have been able to directly induce several differentiated vertebrate cells, including skeletal muscle and skin epidermal cells, to directly convert into unrelated gut lineages, disputing the longstanding model that differentiated cells in vivo are lineage restricted.  In this project, the investigators plan to determine whether most cells in the body, at any age, have the potential to be directly converted into any other cell types, and to uncover and exploit the molecular mechanisms involved in this in vivo cell lineage conversion process.  These studies may pave the way towards a vast new in vivo supply of replacement cells/organs: shifting the paradigm of using an in vitro derivation, stem cell-dependent approach to using an in vivo lineage conversion, stem cell-independent approach to advancing regenerative medicine.

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