AUTHOR=Bejar Nada , Xiao Siyu , Iyer Dinakar , Muili Azeez , Adeleye Adeniyi , McConnell Bradley K. , Schwartz Robert J. 

TITLE=STEMIN and YAP5SA, the future of heart repair?

JOURNAL=Experimental Biology and Medicine

VOLUME=Volume 249 - 2024

YEAR=2024

URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2024.10246

DOI=10.3389/ebm.2024.10246

ISSN=1535-3699

ABSTRACT=This review outlines some of the many approaches taken over a decade or more to repair damaged hearts. We showcase the recent breakthroughs in organ regeneration elicited by reprogramming factors OCT3/4, SOX2, KLF4, and C-MYC (OKSM). Transient OKSM transgene expression rejuvenated senescent organs in mice. 1 OKSM transgenes also caused murine heart cell regeneration. 2 A triplet alanine mutation of the N-terminus of Serum Response Factor's MADS box SRF153(A3), termed STEMIN, and the YAP mutant, YAP5SA synergized and activated OKSM and NANOG in adult rat cardiac myocytes; thus, causing rapid nuclear proliferation and blocked myocyte differentiation. 3 In addition, ATAC seq showed induced expression of growth factor genes FGFs, BMPs, Notchs, IGFs, JAK, STATs and non-canonical Wnts. Injected STEMIN and YAP5SA synthetic modifying mRNA (mmRNA) into infarcted adult mouse hearts, brought damaged hearts back to near normal contractility without severe fibrosis. 4 Thus, STEMIN and YAP5SA mmRNA may exert additional regenerative potential than OKSM alone for treating heart diseases.