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=249

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=<p>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. OKSM transgenes also caused murine heart cell regeneration. 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. In addition, ATAC seq showed induced expression of growth factor genes <italic>FGFs</italic>, <italic>BMPs</italic>, <italic>Notchs</italic>, <italic>IGFs, JAK, STATs</italic> and non-canonical <italic>Wnts.</italic> Injected STEMIN and YAP5SA synthetic modifying mRNA (mmRNA) into infarcted adult mouse hearts, brought damaged hearts back to near normal contractility without severe fibrosis. Thus, STEMIN and YAP5SA mmRNA may exert additional regenerative potential than OKSM alone for treating heart diseases.</p>