Abstract: Compositions containing an effective amount of mesodermal-like multipotent mammalian mononuclear cells that express both CD34 and M-cadherin cell surface markers are used for preventing, treating or reducing the severity of tissue ischemia or an ischemia associated disorder in a mammal. Such uses may include repopulating an in vivo site with new myocytes and/or vascularizing an ischemic or adjacent tissue. Detection of the level and/or distribution of CD34+/M-cadherin+ mesodermal-like precursor cells in a mammalian tissue sample is used to diagnose, among other things, whether transplantation of autologous CD34+/M-cadherin+ mesodermal-like precursor cells to an ischemic site is indicated.

Abstract: Compositions containing an effective amount of mesodermal-like multipotent mammalian mononuclear cells that express both CD34 and M-cadherin cell surface markers are used for preventing, treating or reducing the severity of tissue ischemia or an ischemia associated disorder in a mammal. Such uses may include repopulating an in vivo site with new myocytes and/or vascularizing an ischemic or adjacent tissue. Detection of the level and/or distribution of CD34+/M-cadherin+ mesodermal-like precursor cells in a mammalian tissue sample is used to diagnose, among other things, whether transplantation of autologous CD34+/M-cadherin+ mesodermal-like precursor cells to an ischemic site is indicated.

Abstract: A recombinant adeno-associated virus is used to transduce the cells of a tissue graft ex vivo. More specifically, rAAV encoding a therapeutic protein is delivered to a vascular graft to prevent smooth muscle cell proliferation or thrombosis in the graft. The cells are transfected ex vivo with the recombinant virus carrying a gene known to inhibit the proliferation and migration of vascular smooth muscle cells, thrombosis, and atherosclerosis. The methods can be used for the treatment of restenosis, vascular thrombosis, balloon injury or other vascular pathology.

Abstract: Compositions and methods for gene transfer of cyclooxygenase (COX) isoforms alone or in conjunction with administration of one or more fatty acid substrate for the COX isoform (e.g., dihommo-?-linoleic acid (DGLA)) are disclosed. Methods for enhancing synthesis of the prostaglandins E1 (PGE1) and prostacyclin (PGI2), without marked local production of pro-inflammatory prostaglandin E2 (PGE2) are also disclosed. The compositions and methods are valuable for protection of vascular conduits, kidney function, airway patency, and renal, cardiac, and other allografts, and promoting increased vascular flow, mucus secretion and bicarbonate secretion as protective factors against gastric and duodenal ulcers.

Abstract: A recombinant adeno-associated virus is used to transduce the cells of a tissue graft ex vivo. More specifically, rAAV encoding a therapeutic protein is delivered to a vascular graft to prevent smooth muscle cell proliferation or thrombosis in the graft. The cells are transfected ex vivo with the recombinant virus carrying a gene known to inhibit the proliferation and migration of vascular smooth muscle cells, thrombosis, and atherosclerosis. The methods can be used for the treatment of restenosis, vascular thrombosis, balloon injury or other vascular pathology.

Abstract: A recombinant adenoviral vector encoding the human tissue factor pathway inhibitor (TFPI) gene is disclosed which is useful for transduction of vascular smooth muscle cells at a selected blood vessel site to provide local vascular expression of TFPI. A method of using the transduced hTFPI cDNA as an in vivo antithrombotic agent to provide localized production of hTFPI for protecting an at-risk site against thrombus deposition is also disclosed. Gene therapy using the new TFPI expression vector is also expected to deter the development of chronic vascular stenosis in blood vessels (arteries, veins, arteriovenous shunts, and endovascular grafts) and deterring intimal hyperplasia.

Abstract: Methods for induction of E2F-1 related vascular smooth muscle cell (VSMC) death to limit vascular stenosis or restenosis, to regress atherosclerotic plaque and to prevent atherogenesis are disclosed. Also disclosed is an adenovirus vector containing the E2F-1 gene, and a method of transferring the gene to a vessel or graft. A method of limiting cell proliferation and/or reducing cell numbers includes transferring the E2F-1 gene into VSMC to achieve overexpression of E2F-1 gene product, which drives vascular cells into S-phase and thereby causes their subsequent death.