Methods of treating stroke using stem cell-like menstrual blood cells

• US 9,044,431 B2
• Filed: 05/13/2011
• Issued: 06/02/2015
• Est. Priority Date: 11/13/2008
• Status: Active Grant

• Current Assignee: Augusta University Research Institute, Inc., Cryo-Cell International Incorporated, The United States of America as represented by the Department of Veterans Affairs, Office of the Gen, Medical College of Georgia (University System of Georgia)
• Original Assignee: Cryo-Cell International Incorporated, University of South Florida (State University System of Florida), Medical College of Georgia (University System of Georgia)
• Inventors: Sanberg, Paul R., Borlongan, Cesario V., Allickson, Julie
• Primary Examiner(s): HAYES, ROBERT CLINTON
• Application Number:
  US13/107,391
• Publication Number:
  US 20110268710A1
• Time in Patent Office: 1,481 Days
• US Class Current: 1/1
• 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 cerebral ischemia in a patient comprising:

selecting for CD 117⁺ cells from menstrual blood to form an isolated menstrual blood-derived stem cell enriched cell population;

culturing the menstrual blood-derived stem cell enriched cell population to form an expanded, isolated menstrual blood-derived stem cell population;

selecting the expanded, isolated menstrual blood-derived stem cell population for CXCR4 to form a menstrual blood-derived therapeutic; and

administering a therapeutically effective amount of the menstrual blood-derived therapeutic 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 selecting adherent cells from the isolated menstrual blood-derived stem cell enriched cell population, wherein the adherent cells are selected by

culturing the isolated menstrual blood-derived stem cell enriched cell population;

removing the non-adherent cells from the culture;

wherein the adherent cells remain in the isolated menstrual blood-derived stem cell enriched cell population.

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

m filter.

5. 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 into the patient.

6. 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.

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

8. The method of claim 7, 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.

9. The method of claim 7, wherein the isolated menstrual blood-derived stem cell enriched cell population is administered into the jugular vein.

10. The method of claim 8, wherein the isolated menstrual blood-derived stem cell enriched cell population is administered at 4×

10⁵ cells.

11. The method of claim 9, wherein the isolated menstrual blood-derived stem cell enriched cell population is administered at 4×

10⁶ cells.

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

13. The method of claim 12, wherein the human menstrual blood-derived stem cell population is cultured in DMEM/F12 supplemented with N2 and FGF-2.