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| Expression and Signaling in Mesenchymal and Hematopoietic Stem Cells |
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Adult stem cells have the potential to differentiate into a wide variety of tissue specific cells. These cells can therefore be used to treat a variety of disorders ranging from myocardial infarction to osteoporosis. Although hematopoietic stem cells found in the marrow have been well studied for many decades and are routinely used for treating hematological disorders, there is increased interest in mesenchymal stem cells which are the non hematopoietic stem cells found in the marrow. Although these cells are already being used clinically, we know very little about the mechanisms these cells use to differentiate to different lineages. My group aims to understand these mechanisms using gene expression analysis and use this information for designing better media suitable for targeted differentiation of mesenchymal stem cells.
The goal of my group is to understand mechanisms used by mesenchymal stem cells to differentiate into fat, cartilage and bone. Using detailed analysis of gene expression by microarray, we predicted three signaling pathways critical for differentiation and survival of mesenchymal stem cells. The significance of these pathways was then verified by inhibition of receptor kinases using specific small molecule inhibitors. The figure below shows the effect of TGF-β signaling on mesenchymal stem cells. The microarray data predicted that TGF-β pathway was downregulated in adipogenesis and upregulated in chondrogenesis. In keeping with this prediction, inhibition of TGF-β signaling by SB431542 enhanced the adipogenic differentiation of mesenchymal stem cells and blocked their chondrogenic differentiation. This is a good example of how a prediction made from the array analysis can be verified in an experimental system.
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| Oil Red Staining |
Alician Blue Staining |
-SB431542 +SB431542 |
-SB431542 +SB431542 |
| Adipogenesis |
Chrondrogenesis |
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| TGF-b pathway is downregulated in adipogenic differentiation & upregulated in chondrogenic differentiation of MSC |
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| This project was carried out in collaboration with Invitrogen and identification of these three pathways has led to the development of the first commercially available serum free medium for culturing mesenchymal stem cells. |
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