In vitro study | Despite having little effect on cell proliferation, Thiazovivin treatment significantly enhanced the survival of human embryonic stem cells (hESCs) by more than 30 times after enzymolysis, at the same time, the pluripotency of unique colony morphology, and the expression of typical pluripotency markers, such as alkaline phosphatase (ALP), and normal karyotype, are uniformly maintained. Treatment of dissociated hESCs with Thiazovivin significantly increased their adhesion to artificial basement membrane-or laminin-coated plates within a few hours, while there was no effect on gelatin-coated plates. Thiazovivin treatment increased cell-ECM adhesion-mediated β1 integrin activity, which synergizes with growth factors to promote cell survival. In addition to activating integrins, Thiazovivin, but not Tyrintegin (Ptn), is also able to mediate cell-cell interactions through E-cadherin, protect hESCs from death in ECM-deficient suspensions. Thiazovivin treatment effectively inhibits E-Cadherin Endocytosis, thereby stabilizing cell-surface E-cadherin and restoring cell-cell interactions, this is necessary for hESC to survive in an ECM-free environment. Thiazovivin, but not Tyrintegin (Ptn), inhibits Rho-associated kinase (ROCK) activity at a concentration of 2 μm and protects hESCs, similar to the effect of the widely used selective ROCK Inhibitor Y-27632 at a concentration of 10 μm, Rho-ROCK signaling is shown to regulate cell-ECM and cell-cell adhesion. 1 μm Thiazovivin increased the recombination potency of CB monocytes to induce more than 10-fold pluripotent stem cells (iPSCs). |