Smooth muscle progenitor cells

Abstract

Purified populations of smooth muscle progenitor cells are provided as well as methods of making and using the cells.

What is claimed is:  
     
         1 . An enriched population of adult smooth muscle progenitor cells.  
     
     
         2 . The enriched population of adult smooth muscle progenitor cells of  claim 1 , wherein said cells are positive for VEGF receptors.  
     
     
         3 . The enriched population of adult smooth muscle progenitor cells of  claim 1 , wherein said cells are positive for CD34.  
     
     
         4 . The enriched population of adult smooth muscle progenitor cells of  claim 2 , wherein said cells are positive for CD34, Flt1, and Flk receptor, and negative for the Tie-2 receptor, CD31, vWF, and VE-cadherin.  
     
     
         5 . The enriched population of adult smooth muscle progenitor cells of  claim 1 , wherein said cells are positive for α-actin, myosin heavy chain, and calponin.  
     
     
         6 . The enriched population of adult smooth muscle progenitor cells of  claim 1 , wherein said cells comprise an exogenous nucleic acid encoding an angiogenic growth factor.  
     
     
         7 . The enriched population of adult smooth muscle progenitor cells of  claim 1 , wherein said cell comprise an exogenous nucleic acid encoding VEGF, fibroblast growth factor-4 (FGF-4), a natiuretic peptide, prostacyclin synthase, nitric oxide synthase, angiostatin, endostatin, erythropoietin (EPO), granulocyte/macrophage colony stimulating factor (GM-CSF), an integrin, or an interleukin.  
     
     
         8 . The enriched population of adult smooth muscle progenitor cells of  claim 1 , wherein said cells are human cells.  
     
     
         9 . A method for isolating an enriched population of adult smooth muscle progenitor cells, said method comprising contacting a mixture of mononuclear cells with platelet-derived growth factor and isolating said population of smooth muscle progenitor cells, wherein said cells are positive for CD34, Flt1, and Flk receptor, and negative for the Tie-2 receptor, CD31, vWF, and VE-cadherin.  
     
     
         10 . The method of  claim 9 , wherein said contacting step is performed on a collagen coated substrate.  
     
     
         11 . A method for obtaining an enriched population of adult smooth muscle progenitor cells, said method comprising 
 a) administering a cytokine to a subject to recruit multipotent cells to the peripheral blood of said subject;    b) obtaining mononuclear cells from said subject; and    c) contacting said mononuclear cells with platelet-derived growth factor to enrich said population of adult smooth muscle progenitor cells, wherein said cells are positive for CD34, Flt1, and Flk receptor, and negative for the Tie-2 receptor, CD31, vWF, and VE-cadherin.    
     
     
         12 . The method of  claim 11 , wherein said cytokine is VEGF, FGF, IGF-1, or SDF.  
     
     
         13 . The method of  claim 1   1 , wherein said contacting step is performed on a collagen coated substrate.  
     
     
         14 . A method for stabilizing vulnerable plaques in a patient, said method comprising administering an amount of an enriched population of adult smooth muscle progenitor cells to said patient effective to stabilize vulnerable plaques.  
     
     
         15 . The method of  claim 14 , wherein said enriched population of adult smooth muscle progenitor cells is autologous to said patient.  
     
     
         16 . The method of  claim 14 , wherein said enriched population of adult smooth muscle progenitor cells comprise an exogenous nucleic acid encoding an adhesion molecule, wherein said adhesion molecule is expressed on the cell surface.  
     
     
         17 . The method of  claim 16 , wherein said adhesion molecule is selected from the group consisting of a selectin, an intracellular adhesion molecule, and an extracellular matrix protein.  
     
     
         18 . The method of  claim 17 , wherein said extracellular matrix protein is collagen, fibronectin, laminin, or vitronectin.  
     
     
         19 . The method of  claim 17 , wherein said intracellular adhesion molecule is ICAM or VCAM.  
     
     
         20 . The method of  claim 14 , wherein said population of adult smooth muscle progenitor cells is pretreated with an extracellular matrix protein before administration to said patient.  
     
     
         21 . An implantable medical device comprising an enriched population of adult smooth muscle progenitor cells.  
     
     
         22 . The device of  claim 21 , wherein said cells are positive for CD34, Flt1, and Flk receptor, and negative for Tie-2 receptor, CD31, vWF, and VE-cadherin.  
     
     
         23 . The device of  claim 21 , wherein said device is a stent.  
     
     
         24 . The device of  claim 23 , wherein said stent is coated.  
     
     
         25 . The device of  claim 21 , wherein said device is a vascular graft.  
     
     
         26 . The device of  claim 21 , wherein said device is a hollow tube.  
     
     
         27 . The device of  claim 21 , wherein said cells are human cells.  
     
     
         28 . The device of  claim 21 , wherein said cells comprise an exogenous nucleic acid encoding an angiogenic growth factor.  
     
     
         29 . The device of  claim 21 , wherein said cell comprises an exogenous nucleic acid encoding VEGF, fibroblast growth factor-4 (FGF-4), a natiuretic peptide, prostacyclin synthase, nitric oxide synthase, angiostatin, endostatin, erythropoietin (EPO), granulocyte/macrophage colony stimulating factor (GM-CSF), an integrin, or an interleukin.  
     
     
         30 . A method for monitoring vascular disease in an adult mammal, said method comprising determining the number of smooth muscle progenitor cells in the peripheral blood of said adult mammal, and comparing the number of smooth muscle progenitor cells with a baseline number of smooth muscle progenitor cells in a corresponding control population, wherein an altered number of said smooth muscle progenitor cells relative to said baseline number is indicative of a change in said vascular disease.  
     
     
         31 . The method of  claim 30 , wherein said vascular disease is atherosclerosis.  
     
     
         32 . The method of  claim 30 , wherein said vascular disease comprises vulnerable plaque.  
     
     
         33 . The method of  claim 30 , wherein said vascular disease comprises unstable plaque.