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

• US 7,153,501 B2
• Filed: 07/25/2003
• Issued: 12/26/2006
• Est. Priority Date: 07/25/2002
• Status: Expired due to Fees

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Da Silva, Karen, Otani, Atsushi, Friedlander, Martin
• Primary Examiner(s): Nguyen, Quang
• Application Number:
  US10/628,783
• Publication Number:
  US 20040197902A1
• Time in Patent Office: 1,250 Days
• Field of Search: 424/93.21, 435/455, 435/325, 435/320.1, 536/23.5
• US Class Current: 424/93.21
• 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 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
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• 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, bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin⁻ HSC) contain endothelial progenitor cells (EPC) capable of forming retinal blood vessels. At least about 50% of the cells in the isolated Lin⁻ HSC population include cell surface markers for CD31 and c-kit. Up to about 8% of the cells can include the Sca-1 cell marker, and up to about 4% of the cells can include the Flk-1/KDR marker. The isolated Lin⁻ HSC populations of the present invention are useful for treatment of ocular vascular diseases. The isolated Lin⁻ HSC populations that have been transfected with therapeutically useful genes are also provided, which are useful for delivering genes to the eye for cell-based gene therapy.

Claims

1. An isolated and transfected lineage negative hematopoietic stem cell population containing endothelial progenitor cells in which at least about 50% of all cells in said stem cell population express cell markers for CD31 and c-kit, and not more than about 1% of all cells in said stem cell population express the Tie-2 marker, and where the cells of said stem cell population are transfected with a DNA encoding an anti-angiogenic peptide, an anti-angiogenic protein or an anti-angiogenic protein fragment.

2. The transfected stem cell population of claim 1 wherein the anti-angiogenic protein fragment is an anti-angiogenic protein fragment of tryptophanyl-tRNA synthetase (TrpRS).

3. The transfected stem cell population of claim 2 wherein the anti-angiogenic protein fragment of TrpRS is T2-TrpRS.