期刊
CELL TRANSPLANTATION
卷 23, 期 4-5, 页码 657-668出版社
SAGE PUBLICATIONS INC
DOI: 10.3727/096368914X678391
关键词
Embryonic stem cells (ESCs); Induced pluripotent stem cells (iPSCs); Salvia miltiorrhiza; Salvianolic acid B (Sal B)
资金
- Taiwan Department of Health Clinical Trial and Research Center of Excellence [DOH102-TD-B-111-004]
- China Medical University [CMU100-TS-16]
- Republic of China National Science Council [NSC 101-2314-B-039-009-MY2]
- Gwoxi Stem Cell Applied Technology Co., Ltd. [10242643]
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are considered the most powerful in terms of differentiating into three-germ-layer cells. However, maintaining self-renewing ESCs and iPSCs in vitro requires leukemia-induced factor (LIP), an expensive reagent. Here we describe a less expensive compound that may serve as a LIP substitute-salvianolic acid B (Sal B), a Salvia miltiorrhiza extract. We found that Sal B is capable of upregulating Oct4 and Sox2, two genes considered important for the maintenance of ESC pluripotency. Our MTT data indicate that instead of triggering cell death, Sal B induced cell proliferation, especially at optimum concentrations of 0.01 nM and 0.1 nM. Other results indicate that compared to non-LIF controls, Sal B-treated ESCs expressed higher levels of several stem cell markers while still maintaining differentiation into three-germ-layer cells after six passages. Further, we found that Sal B triggers the Jak2-Stat3 and EGFR ERK1/2 signaling pathways. Following Sal B treatment, (a) levels of phosphorylated (p)-Jak2, p-Stat3, p-EGFR, and p-ERK proteins all increased; (b) these increases were suppressed by AG490 (a Jak2 inhibitor) and ZD1839 (an EGFR inhibitor); and (c) cytokines associated with the Jak2 Stat3 signaling pathway were upregulated. Our findings suggest that Sal B can be used as a LIP replacement for maintaining ESC pluripotency while increasing cell proliferation.
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