This patent covers the use of agonists of LPL receptors to inhibit differentiation of embryonic stem cells.
The inhibition of embryonic stem cell differentiation is important since the innate tendency of these cells is to differentiate when grown in absence of specific feeder cells and cytokines. While companies such as Geron have patents on specific culture systems that inhibit differentiation using FGF and extracellular matrix formulations, the inventors of this patent have identified that chemicals such as Sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) may be used to inhibit differentiation of as an additive to culture media. Why?
S1P and LPA, as well as numerous other lysophospholipids mediate their biological activities by activating specific lysophospholipid G-protein coupled receptors (LPL receptors). The inventors found that these LPL receptors are involved in blocking differentiation events in embryonic stem cells.
There seems to be an increasing interest in the relation between varous lysophospholipids and stem cells. For example, patent # 7,241,812 covers S1P receptor modulating components and uses of these compounds in altering stem cell activity. Interestingly, direct administration of S1P has been demonstrated to induce chemoattraction of mesenchymal stem cells.
View this patent on the USPTO website.
Dear Renita,
This warburg effect is also the same way that ketone bodies can selectively kill glioma cells from what i remember. Also it is how ozone therapy works against cancer, by destroying the cells that use lactic acid for their metabolism instead of using the normal glycolytic cycle.
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Renita said...
The proliferation and differentiation of mesenchymal stem cells is influenced by the oxygen tension. To understand this effect and predict cell behaviour within 3D culture environments, this study measured the oxygen consumption, glucose consumption and lactate production. The mean consumption rate per cell for human mesenchymal stem cells ranged from 44.6 - 93 fmoles/hr/cell at passage 3. There was no significant difference in the oxygen consumption rate between P2-P4. The production of lactate suggests that these cells are preferentially glycolytic, despite the presence of oxygen, a phenomenon known as the Warburg effect.
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Renita
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