Claims for Patent: 7,410,797

Summary for Patent: 7,410,797

Title:	Meningeal-derived stem cells
Abstract:	Stem cell lines derived from meningeal tissue such as dura mater, pia mater, or arachnoid mater, are disclosed. In various embodiments, the stem cell lines include greater than 80%, greater than 90%, or greater than 99% of pluripotent meningeal-derived stem cells. In other embodiments, the stem cell lines are induced to form nerve cells, bone cells, cartilage cells, Schwann cells, adipocytes, fibroblasts, or melanocytes with various inducing agents, such as antioxidants, steroid hormones, laminin, or various growth factors. Derivation of the current stem cell lines is accomplished through explantation or enzymatic dissociation of meningeal tissue, followed by expansion to large populations using growth media.
Inventor(s):	Ogle; Roy C. (Earlysville, VA), Tholpady; Sunil (Charlottesville, VA)
Assignee:
Application Number:	10/458,102
Patent Claims:	1. A composition, comprising: a population of differentiated cells of a cell type selected from the group consisting of a nerve cell, a bone cell, a cartilage cell, a Schwann cell, an adipocyte, a fibroblast, a melanocyte and combinations thereof; and a population of adult stem cells isolated from the meninges, wherein said population of differentiated cells is obtained by a process, comprising: providing a population of adult stem cells isolated from the meninges; and inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate into said population of differentiated cells. 2. The composition of claim 1, wherein said cell type is a nerve cell and wherein inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate comprises culturing said population of stem cells isolated from the meninges with a nerve cell inducing agent selected from the group consisting of antioxidant treatment, steroid hormone, vitamin A, retinal, retinaldehyde, retinoic acid, 1,25-dihydroxy vitamin D.sub.3, an agent capable of stimulating intracellular cyclic AMP and combinations thereof. 3. The composition of claim 2, wherein said nerve cell inducing agent is an antioxidant treatment comprising an antioxidant selected from the group consisting of .beta.-mercaptoethanol, butylated hydroxyanisole (BHA), dithiothreitol (DTT), dithioerythritol, tributylphosphine, iodoacetamide, tris-phosphine HCl, deoxythymidine-triphosphate trilithium salt, diethylthiatricarbocyanine perchiorate, diethylthiatricarbocyanine iodide and combinations thereof. 4. The composition of claim 2, wherein said nerve cell inducing agent is a steroid hormone selected from the group consisting of dexamethasone, pregnenolone, aldosterone, testosterone, estrad iol, cortisol and combinations thereof. 5. The composition of claim 4, wherein said steroid hormone is dexamethasone. 6. The composition of claim 2, wherein said nerve cell inducing agent is selected from the group consisting of vitamin A, retinol, retinaldehyde, retinoic acid, 1,25-dihydroxy vitamin D.sub.3 and combinations thereof. 7. The composition of claim 1, wherein said cell type is a bone cell, and wherein inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate comprises culturing said population of stem cells isolated from the meninges with a bone cell inducing agent comprising laminin. 8. The composition of claim 1, wherein said cell type is a bone cell, and wherein inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate comprises culturing said population of stem cells isolated from the meninges with a bone cell inducing agent selected from the group consisting of organic phosphates, inorganic phosphates, ascorbic acid and combinations thereof. 9. The composition of claim 1, wherein said cell type is a cartilage cell, and wherein inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate comprises culturing said population of stem cells isolated from the meninges with a cartilage cell inducing agent selected from the group consisting of an insulin-selenium-transferrin composition, transforming growth factor (TGF)-.beta.1 and combinations thereof. 10. The composition of claim 1, wherein said cell type is a Schwann cell, and wherein inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate comprises using a Schwann cell inducing treatment regimen, comprising: administering to said population of stem cells isolated from the meninges a first treatment, comprising Dulbecco's modified eagle medium (DMEM) and basal medium eagle (BME); and administering to said population of stem cells isolated from the meninges a second treatment, comprising DMEM, fetal bovine serum (FBS) and retinoid acid. 11. The composition of claim 10, wherein said treatment regimen further comprises: administering to said population of stem cells isolated from the meninges a third treatment, comprising DMEM, FBS, forskolin (FSK), heregulin (HER), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF). 12. The composition of claim 11, wherein said first treatment is administered for about one day, said second treatment is administered for about three days and said third treatment is administered for about five days. 13. The composition of claim 1, wherein said cell type is a Schwann cell, and wherein inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate comprises culturing said population of stem cells isolated from the meninges with a Schwann cell inducing agent that stimulates intracellular cyclic AMP. 14. The composition of claim 1, wherein said cell type is an adipocyte, and wherein inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate comprises culturing said population of stem cells isolated from the meninges with an adipocyte inducing agent comprising dexamethasone, insulin, indomethacin and isobutyl-methylxanthine (IBMX). 15. The composition of claim 1, wherein said cell type is a fibroblast, and wherein inducing greater than 60% of said population of stem cells isolated from the meninges to differentiate comprises culturing said population of stem cells isolated from the meninges with a fibroblast inducing agent comprising ascorbic acid. 16. The composition of claim 1, wherein said population of stem cells isolated from the meninges is obtained by a method, comprising: obtaining meningeal tissue from a subject; washing said meningeal tissue in a physiologic buffer to produce washed meningeal tissue; and placing said washed meningeal tissue on a culture substrate comprising a growth medium to culture said meningeal-derived stem cells. 17. The composition of claim 16, wherein said method further comprises: placing said washed meningeal tissue in a solution comprising said physiologic buffer and collagenase to produce dissociated meningeal tissue; and recovering said dissociated meningeal tissue, and wherein placing said washed meningeal tissue on a culture substrate comprising a growth medium to culture said stem cells isolated from the meninges comprises plating said dissociated meningeal tissue onto a culture substrate comprising a growth medium. 18. The composition of claim 16, wherein obtaining said meningeal tissue is performed by biopsy from said subject, aseptic removal from said subject or both. 19. The composition of claim 16, wherein said physiologic buffer is selected from the group consisting of phosphate buffered saline (PBS), Hanks balanced salt solution and combinations thereof. 20. The composition of claim 17, wherein said culture substrate is selected from the group consisting of a tissue culture plate plastic, a laminin-covered substrate, a polyamino acid, a fibronectin, a type I collagen and combinations thereof. 21. The composition of claim 16, wherein said growth medium comprises Dulbecco's modified eagle medium (DMEM), about 10% fetal bovine serum (FBS) and about 1% glutamine.

Details for Patent 7,410,797

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2022-06-11