Uses and isolation of stem cells from bone marrow

• US 9,155,762 B2
• Filed: 10/30/2008
• Issued: 10/13/2015
• Est. Priority Date: 12/08/2005
• Status: Active Grant

• Current Assignee: University of Louisville
• Original Assignee: University of Louisville
• Inventors: Ratajczak, Mariusz, Kucia, Magdalena, Ratajczak, Janina, Bolli, Roberto
• Primary Examiner(s): Noble, Marcia S
• Application Number:
  US12/740,718
• Publication Number:
  US 20110189136A1
• Time in Patent Office: 2,539 Days
• US Class Current: 1/1
• CPC Class Codes: A61B 10/00 Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis vaccination prophylaxis, vaccination therapy A61B17/20; Sex determination; Ovulation-period determination menstruation tables G06C3/00; Throat striking implements
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/34 Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes vascular smooth muscle A61K35/44
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: C12N 5/0607 Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

The presently disclosed subject matter provides populations of stem cells that are purified from bone marrow, peripheral blood, and/or other sources. Also provided are methods of using the stem cells for treating tissue and/or organ damage in a subject.

Claims

1. A method of treating an injury to a cardiac tissue in a subject, the method comprising administering to the subject a composition comprising isolated CD34⁺/lin⁻

/CD45⁻

or Sca-1⁺/lin⁻

/CD45⁻

stem cells from bone marrow in a pharmaceutically acceptable carrier, in an amount and via a route sufficient to engraft at least a fraction of the stem cells in the cardiac tissue and differentiate therein, wherein the injury is myocardial ischemia or a myocardial infarction.

2. The method of claim 1, wherein the isolated stem cells are isolated from bone marrow or peripheral blood, wherein the stem cells isolated from peripheral blood are stems cells that have been mobilized into the peripheral blood from bone marrow.

3. The method of claim 1, wherein the stem cells comprise Sca-1⁺/lin⁻

/CD45⁻

and express at least one of SSEA-1, Oct-4, Rex-1, and Nanog, or comprise CD34⁺/lin⁻

/CD45⁻

and express at least one of SSEA-4, Oct-4, Rex-1, and Nanog.

4. The method of claim 1, wherein the stem cells comprise CXCR4⁺ and/or CD133⁺.

5. The method of claim 1, wherein the subject is a mammal.

6. The method of claim 5, wherein the mammal is a mouse or a human.

7. The method of claim 1, further comprising differentiating the CD34⁺/lin⁻

/CD45⁻

or Sca-1⁺/lin⁻

/CD45⁻

bone marrow stem cells in the composition to produce cardiomyocytes in the composition prior to administering the composition.

8. The method of claim 1, wherein the stem cells express one or more markers selected from the group consisting of Nsx2.5/Csx, and GATA-4.

9. The method of claim 1, wherein the stem cells comprise a stem cell for a myocardial cell.

10. The method of claim 1, wherein CD34⁺/lin⁻

/CD45⁻

or Sca-1⁻

/lin⁻

/CD45⁻

stem cells are administered directly to the myocardium.

11. The method of claim 1, wherein the route of administration is intramyocardial injection.

12. The method of claim 1, wherein at least 10,000 stem cells are administered.

13. The method of claim 1, wherein the route of administration is parenteral administration.

14. The method of claim 1, wherein at least 10,000 stem cells are administered and the route of administration is parenteral administration.

15. The method of claim 14, wherein the isolated stem cells are isolated from bone marrow or peripheral blood, wherein the stem cells isolated from peripheral blood are stems cells that have been mobilized into the peripheral blood from bone marrow.