PT  - JOURNAL ARTICLE
AU  - Avani Yeola
AU  - Shruthi Subramanian
AU  - Rema A. Oliver
AU  - Christine A. Lucas
AU  - Julie A. I. Thoms
AU  - Feng Yan
AU  - Jake Olivier
AU  - Diego Chacon
AU  - Melinda L. Tursky
AU  - Tzongtyng Hung
AU  - Carl Power
AU  - Philip Hardy
AU  - David D. Ma
AU  - Joshua McCarroll
AU  - Maria Kavallaris
AU  - Luke B. Hesson
AU  - Dominik Beck
AU  - David J. Curtis
AU  - Jason W.H. Wong
AU  - Edna C. Hardeman
AU  - William R. Walsh
AU  - Ralph Mobbs
AU  - Vashe Chandrakanthan
AU  - John E. Pimanda
TI  - Induction of Muscle Regenerative Multipotent Stem Cells from Human Adipocytes by PDGF-AB and 5-Azacytidine
AID  - 10.1101/2020.06.04.130872
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.04.130872
4099  - http://biorxiv.org/content/early/2020/06/05/2020.06.04.130872.short
4100  - http://biorxiv.org/content/early/2020/06/05/2020.06.04.130872.full
AB  - Terminally differentiated murine osteocytes and adipocytes can be reprogrammed using platelet-derived growth factor–AB and 5-Azacytidine into multipotent stem cells with stromal cell characteristics. To generate a product that is amenable for therapeutic application, we have modified and optimised culture conditions to reprogram human adipocytes into induced multipotent stem cells (iMS) and expand them in vitro. The basal transcriptomes of adipocyte-derived iMS cells and matched adipose-tissue-derived mesenchymal stem cells were remarkably similar. However, there were distinct changes in histone modifications and CpG methylation at cis-regulatory regions consistent with an epigenetic landscape that was primed for tissue development and differentiation. In a non-specific tissue injury xenograft model, iMS cells contributed directly to new muscle, bone, cartilage and blood vessels with no evidence of teratogenic potential. In a cardiotoxin muscle injury model, iMS cells contributed specifically to satellite cells and myofibres without ectopic tissue formation. Taken together, human adipocyte derived iMS cells regenerate tissues in a context dependent manner without ectopic or neoplastic growth.Competing Interest StatementVC and JEP are named inventors on a patent &#039;A method of generating cells with multi-lineage potential&#039; (US 9982232, AUS 2013362880).