Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow, heart, liver, muscle, lung, derma, kidney, and fat

Abstract

Previously, we reported that a cell population derived from human fetal bone marrow (BM), termed here Flk1⁺CD34^- postembryonic pluripotent stem cells (PPSCs) that have the characteristics of mesenchymal stem cells (MSCs), could differentiate into ectodermal, endodermal and mesodermal cell types at the single cell level in vitro, and that these cells could also differentiate into the epithelium of liver, lung, gut, as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we further isolated pluripotent stem cells from human fetal heart, liver, muscle, lung, derma, kidney, and fat and then analyzed the characteristics and function of these stem cells. It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1⁺CD34^- PPSCs, i.e. Flk1 and CD44 positive, GlyA, CD34, CD45, class I-HLA and HLA-DR negative. Morphologically, these cells were fibroblast-like and the doubling time was about 30 h. More importantly, culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes, osteocytes, neurons, glial cells and hepatocytes. These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1⁺CD34^- PPSCs can be selected and cultured from tissues other than the BM. This phenomenon may help explain the stem cell plasticity  found in multiple human tissues. In addition, as fetal BM-derived Flk1⁺CD34^- PPSCs, these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage differentiation even after being expanded for more than 40 population doublings in vitro. Thus, they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.