METHODS OF TREATING STROKE USING STEM CELL-LIKE MENSTRUAL BLOOD CELLS

• US 20110268710A1
• Filed: 05/13/2011
• Published: 11/03/2011
• Est. Priority Date: 11/13/2008
• Status: Active Grant

• Current Assignee: Cryo-Cell International Incorporated, The United States of America Represented by The Department of Veterans Affairs, Augusta University Research Institute, Inc. (University System of Georgia), Medical College of Georgia (University System of Georgia)
• Original Assignee: Saneron CCEL Therapeutics, Inc., University of South Florida (State University System of Florida), Medical College of Georgia (University System of Georgia)
• Inventors: Borlongan, Cesario V., Allickson, Julie, Sanberg, Paul R.
• Granted Patent: US 9,044,431 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 35/14 Blood; Artificial blood perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A cell type that is a complete match of the transplant recipient appears as an optimal scenario to open treatment options to a large patient population with minimal complications. The use of autologous bone marrow or umbilical cord blood has been proposed as a good source of stem cells for cell therapy. Menstrual blood is found to be another important source of stem cells. Assays of cultured menstrual blood reveal that they express embryonic like-stem cell phenotypic markers and neuronal phenotypic markers under appropriate conditioned media. Oxygen glucose deprivation stroke models show that OGD-exposed primary rat neurons, co-cultured with menstrual blood-derived stem cells or exposed to the media from cultured menstrual blood, exhibited significantly reduced cell death. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats.

Claims

1. A method of treatment of ischemia in a patient comprising administering a therapeutically effective amount of an isolated menstrual blood-derived stem cell enriched cell population into the patient.

2. The method of claim 1, wherein the isolated menstrual blood-derived stem cell enriched cell population was administered within 2 hours of stroke.

3. The method of claim 1, further comprising culturing the menstrual blood-derived stem cell enriched cell population prior to administration into the patient.

4. The method of claim 3, wherein the isolated menstrual blood-derived stem cell enriched cell population was selected for CD 117.

5. The method of claim 3, wherein the isolated menstrual blood-derived stem cell enriched cell population was selected for adherent cells.

6. The method of claim 1, wherein the isolated menstrual blood-derived stem cell enriched cell population was filtered with a 100 μ

m filter.

7. The method of claim 1, wherein the isolated menstrual blood-derived stem cell enriched cell population was treated with a plurality of antibiotics prior to administration.

8. The method of claim 1, wherein the isolated menstrual blood-derived stem cell enriched cell population excretes at least one trophic factor selected from the group consisting of vascular endothelial growth factor, brain-derived neurotrophic factor, and neurotrophin-3.

9. The method of claim 1, wherein the isolated menstrual blood-derived stem cell enriched cell population is administered intravenously or intracranially.

10. The method of claim 9, wherein the isolated menstrual blood-derived stem cell enriched cell population is implanted 0.5 mm anterior to the bregma, 2.8 mm lateral to midline, and 5.0 mm below the dural surface.

11. The method of claim 9, wherein the isolated menstrual blood-derived stem cell enriched cell population is administered into the jugular vein.

12. The method of claim 10, wherein the isolated menstrual blood-derived stem cell enriched cell population is administered at 4×

10⁵ cells.

13. The method of claim 11, wherein the isolated menstrual blood-derived stem cell enriched cell population is administered at 4×

10⁶ cells.

14. The method of claim 1, further comprising culturing the human menstrual blood-derived stem cell population in neural induction medium and retinoic acid.

15. The method of claim 14, wherein the human menstrual blood-derived stem cell population is cultured in DMEM/F12 supplemented with N2 and FGF-2.

16. A method of treatment of ischemia in a patient comprising:

isolating a population of menstrual blood-derived stem cells;

incubating the population of menstrual blood-derived stem cells, such that the population of menstrual blood-derived stem cells excrete at least one trophic factor selected from the group consisting of vascular endothelial growth factor, brain-derived neurotrophic factor, and neurotrophin-3;

collecting the excreted at least one trophic factor; and

administering the at least one trophic factor into the patient.

17. The method of claim 16, wherein the human menstrual blood-derived stem cell population is cultured in DMEM/F12 supplemented with N2 and FGF-2.