Hematopoietic stem cells and methods of treatment of neovascular eye diseases therewith

• US 7,838,290 B2
• Filed: 04/28/2004
• Issued: 11/23/2010
• Est. Priority Date: 07/25/2002
• Status: Expired due to Fees

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Otani, Atsushi, Moreno, Stacey, Da Silva, Karen (Irvine, Friedlander, Martin
• Primary Examiner(s): Nguyen; Quang
• Application Number:
  US10/833,743
• Publication Number:
  US 20050063961A1
• Time in Patent Office: 2,400 Days
• Field of Search: None
• US Class Current: 435/372
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors
• CPC Class Codes: C12N 5/0692 Stem cells; Progenitor cells; Precursor cells

Abstract

Isolated, mammalian, adult bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin⁻ HSCs) contain endothelial progenitor cells (EPCs) capable of rescuing retinal blood vessels and neuronal networks in the eye. Preferably at least about 20% of the cells in the isolated Lin⁻ HSCs express the cell surface antigen CD31 and not more than about 1 percent of the cells express Tie-2. The isolated Lin⁻ HSC populations are useful for treatment of ocular vascular diseases.

Claims

1. An isolated, CD133 positive human lineage negative hematopoietic stem cell population, which comprises human hematopoietic stem cells and endothelial progenitor cells, wherein the stem cell population is isolated by the steps of:

(a) labeling a plurality of isolated human bone marrow monocytes with a panel of biotin-conjugated antibodies selective for lineage surface antigens CD2, CD3, CD4, CD11a, Mac-1, CD14, CD16, CD19, CD24, CD33, CD38, CD45RA, CD64, CD68, CD86, and CD235a;

(b) removing monocytes that are positive for said lineage surface antigens from the labeled plurality of isolated human bone marrow monocytes produced in step (a) to form a lineage negative stem cell population;

(c) labeling the lineage negative stem cell population with a CD133 antibody; and

(d) recovering a population of human CD133 positive, lineage negative hematopoietic stem cells containing endothelial progenitor cells therefrom.

2. The isolated stem cell population of claim 1 wherein the monocytes are obtained from adult human bone marrow.

3. The isolated stem cell population of claim 1 further including a cell culture medium.