Patent
Method for selecting mevalonate synthesis modulators using cells derived from human pluripotent cells
| العنوان: | Method for selecting mevalonate synthesis modulators using cells derived from human pluripotent cells |
|---|---|
| Patent Number: | 8,759,022 |
| تاريخ النشر: | June 24, 2014 |
| Appl. No: | 13/805547 |
| Application Filed: | June 20, 2011 |
| مستخلص: | The invention provides a method for selecting pharmaceutical compounds affecting mevalonate or cholesterol. The method having a step for putting into contact with the pharmaceutical compounds to be tested, cells of the MSC type obtained by a method for producing cells of the MSC type from human pluripotent cells or from induced stem cells, including a step for cultivating human pluripotent cells or induced stem cells in a culture medium of: 1) one or more growth factors selected from FGFs, HGF, PDGFs, EGF, herugulins and VEGFs; and 2) one or more antioxidants selected from ascorbic acid and its derivatives, vitamin E and N-acetylcysteine. |
| Inventors: | Pinset, Christian (Paris, FR) |
| Assignees: | Centre d'Etude des Cellules Souches (Evry, FR) |
| Claim: | 1. A method for selecting pharmaceutical compounds enhancing effects of inhibition of synthesis of mevalonate wherein the selected compounds can enhance cell toxicity in the presence of inhibitors of the synthesis of mevalonate comprising a step for contacting the cells with the pharmaceutical compounds to be tested, wherein the cells are obtained by a method for producing cells of the MSC type from human pluripotent cells or from induced stem cells comprising cultivating human pluripotent cells or induced stem cells in a culture medium comprising a) one or more growth factors selected from FGFs, HGF, PDGFs, EGF, herugulins and VEGFs, and b) one or more antioxidants selected from ascorbic acid and its derivatives, vitamin E and N-acetylcysteine. |
| Claim: | 2. A method for selecting pharmaceutical compounds according to claim 1 , wherein the cells of the MSC type obtained from induced stem cells are cultivated in the presence of 1% of fetal calf serum. |
| Claim: | 3. A method for selecting pharmaceutical compounds according to claim 1 , wherein the cells are contacted with an inhibitor of HMG CoA reductase, and other reductases, or simvastatin. |
| Claim: | 4. A method for selecting pharmaceutical compounds according to claim 1 , comprising a first screening that allows isolation of the molecules which enhance toxicity in the presence of cells treated with statins and then a counter-screening is performed on the thereby isolated molecules from the first screening in order to remove the molecules which have toxicity in the absence of statins. |
| Current U.S. Class: | 435/29 |
| Patent References Cited: | 2006/0258003 November 2006 Pinset 2009/0081784 March 2009 Vodyanyk et al. 2010/0166713 July 2010 Dalton et al. 2010/0267135 October 2010 Sakurada et al. WO-2004/055174 July 2004 WO-2005/111197 November 2005 WO-2008/094597 August 2008 WO-2008/150498 December 2008 |
| Other References: | McNeish John. Embryonic Stem Cells in Drug Discovery. Nature Reviews Drug Discovery 3:70-80, Jan. 2004. cited by examiner Takamizawa S. et al. Effects of Ascorbic Acid and Ascorbic Acid 2-Phosphate . . . Cell Biology International 28(4)255-265, 2004. cited by examiner Boyd, N. L., et al.; “Human Embryonic Stem Cell-Derived Mesoderm-like Epithelium Transitions to Mesenchymal Progenitor Cells;” Tissue Engineering Part A; vol. 15, No. 8; dated Jan. 15, 2009. cited by applicant De Peppo, G. M., et al.; “Human Embryonic Mesodermal Progenitors Highly Resemble Human Mesenchymal Stem Cells and Display High Potential for Tissue Engineering Applications;” Tissue Engineering Part A; vol. 16, No. 7; dated Mar. 10, 2010. cited by applicant International Search Report for Application No. PCT/IB2011/052680; dated Dec. 1, 2011. cited by applicant Karlsson, C., et al.; “Human embryonic stem cell-derived mesenchymal progenitors—Potential in regenerative medicine;” Stem Cell Research; vol. 3, No. 1; dated May 7, 2009. cited by applicant Kitagawa, M., et al.; “Differentiation of mesodermal cells from pluripotent stem cells;” International Journal of Hematology; vol. 91, No. 3; dated Mar. 12, 2010. cited by applicant |
| Primary Examiner: | Gitomer, Ralph |
| Attorney, Agent or Firm: | Alston & Bird LLP |
| رقم الانضمام: | edspgr.08759022 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |