MEISi-2 is a specific MEISi inhibitor that inhibits the meis luciferase reporter gene in vitro and induces MEIS-dependent hematopoietic stem cell maintenance and self-renewal, which can be used in research areas such as cardiac injury, hematopoietic problems, bone marrow transplantation and cancer.

In studies of neonatal rat cardiomyocytes (RNCMs) and human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, treatment with MEISi-2 (5 μM) was performed. In RNCMs, the proportion of cells positive for the proliferation markers phospho-histone H3 (Ph3) and Aurora B significantly increased following treatment. Specifically, the proliferation rate of Ph3⁺/TnnT2⁺ cells increased by up to 4.5-fold, while the proportion of Aurora B⁺/TnnT2⁺ cells doubled. Meanwhile, the expression levels of MEIS1 target genes, including Hif-1α, Hif-2α, and p21, were significantly downregulated [1].

In a mouse model, MEISi-2 (at a concentration of 10µM) was administered intraperitoneally on days 1, 4, and 7 (100µL per injection), and bone marrow cells were collected on day 10 for analysis. The Results showed that this treatment significantly upregulated the expression of hematopoietic stem cell markers c-Kit+ and Sca-1+, with the numbers of c-Kit+, Sca-1+, and LSKCD34lowHSC cells increasing approximately 2-fold, 1.5-fold, and 3-fold, respectively. Meanwhile, MEISi-2 treatment downregulated the expression of key cell cycle inhibitors such as Meis1, Hif-2α, and p16. The study indicates that MEISi-2 effectively inhibits MEIS protein function and promotes an increase in hematopoietic stem cell numbers by modulating gene expression[2].