sRNA Induces the Large-scale Transdetermination of Mesenchymal Stem Cells into HEMAtopoietic Stem Cells in Human.

Mesenchymal stem cells (MSCs) can differentiate into cells of bone, endothelium, adipose tissue, cartilage, muscle, and brain. However, whether they can transdeterminate into hEMAtopoietic stem cells (HSCs) rEMAins unsolved. We report here that a subpopulation of human MSCs that are CD44+,CD29+, CD105+, CD166+,CD133-,CD34- could differentiate into hEMAtopoietic stem cells (CD150+/CD133+/CD34+) and their descending blood cells in vitro, when transfected with new endogenous shRNAs The sRNA was high-effectively delivered into MSCs by a novel peptide means. These induced MSC-HSCs could form different types of hEMAtopoietic colonies as nature-occurring HSCs did. Upon transplantation into sublethally irradiated NOD/SCID mice, these MSC-HSCs engrafted and differentiated into all hEMAtopoietic lineages such as erythrocytes, lymphocytes, myelocytes and thrombocyte. More importantly, these induced HSCs could successfully engraft and effectively function in patients with severe aplastic anemia. Furthermore, we demonstrated the first evidence that the transdetermination of MSCs was induced by acetylation of histone proteins and activation of many transcriptional factors. Together, our findings identify the sRNAs that dictates a directed differentiation of MSCs toward HSCs and open up a new source for HSCs used for the treatment of blood diseases and artificial stem cell-made blood.