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.
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Interplays between Mesenchymal Stem Cells and Immune Responses
Mesenchymal stem cells (MSCs) exist in almost all tissues and are crucial in maintaining the cellular homeostasis of multicellular organisms. They provide the ultimate cell source for tissue repair and regeneration. Under pathological conditions, these cells are awakened, activated, and mobilized to damaged tissue sites. Since tissue damages are often accompanied by inflammatory factors, from both innate immune response and adaptive immune response, it is sensible that MSCs delicately interact with inflammatory factors at the sites of tissue damages.
Depending on the type and persistence of the inflammatory factors, the activated MSCs could lead either to complete or partial tissue repair, or to chronic inflammation and further tissue damage, such as cancer and fibrosis. Indeed, recent studies have shown that there is a bidirectional interaction between MSCs and inflammatory cells and cytokines. However, much information of this information remains to be elucidated. Further investigations in this newly emerging exciting research area will undoubtedly lead to better understanding of pathogenesis of various diseases and novel treatment strategies.
Cell and chemical biology of mitosis