Sca-1+ Cells from Fetal Heart with High Aldehyde Dehydrogenase Activity Exhibit Enhanced Gene Expression for Self-Renewal, Proliferation, and Survival

摘要

Stem/progenitor cells from multiple tissues have been isolated based on enhanced activity of cytosolic aldehyde dehydrogenase (ALDH) enzyme. ALDH activity has emerged as a reliable marker for stem/progenitor cells, such that ALDHbright/high cells from multiple tissues have been shown to possess enhanced stemness properties (self-renewal and multipotency). So far though, not much is known about ALDH activity in specific fetal organs. In this study, we sought to analyze the presence and activity of the ALDH enzyme in the stem cell antigen-1-positive (Sca-1+) cells of fetal human heart. Biochemical assays showed that a subpopulation of Sca-1+ cells (15%) possess significantly high ALDH1 activity. This subpopulation showed increased expression of self-renewal markers compared to the ALDHlow fraction. The ALDHhigh fraction also exhibited significant increase in proliferation and pro-survival gene expression. In addition, only the ALDHhigh and not the ALDHlow fraction could give rise to all the cell types of the original population, demonstrating multipotency. ALDHhigh cells showed increased resistance against aldehyde challenge compared to ALDHlow cells. These results indicate that ALDHhigh subpopulation of the cultured human fetal cells has enhanced self-renewal, multipotency, high proliferation, and survival, indicating that this might represent a primitive stem cell population within the fetal human heart.