Perivascular mesenchymal precursor cell induced blood vessel formation

Abstract

Mesenchymal precursors cells have been isolated from perivascular niches from a range of tissues utilizing a perivascular marker. A new mesenchymal precursor cell phenotype is described characterized by the presence of the perivascular marker 3G5, and preferably also alpha smooth muscle actin together with early developmental markers such as STRO-1 and CD146/MUC18. The perivascular mesenchymal precursor cell is shown to induce neovascularisation and improvement in cardiac function. Suitable administration of preparations of the mesenchymal precursor cells are useful for treatment of cardiovascular diseases, cerebrovascular diseases and peripheral vascular diseases.

1 .- 40 . (canceled) 
     
     
         41 . A method of repairing damaged tissue in a human subject in need of such repair, the method comprising:
 (a) providing an enriched population of MPC, and   (b) administering to the subject an amount of the enriched population of MPCs effective to repair the damaged tissue, wherein said tissue is not a cardiac tissue.   
     
     
         42 . A method of repairing damaged tissue in a human subject in need of such repair, the method comprising:
 (a) expanding the enriched MPC of  claim 41  in culture, and   (b) contacting an effective amount of the expanded cells with the damaged tissue of said subject.   
     
     
         43 . The method of  claim 41  or  42  wherein the damaged tissue is selected from the group consisting of muscle, brain, kidney and lung. 
     
     
         44 . The method of  claim 41  wherein said subject suffers from cerebrovascular ischemia, renal ischemia, pulmonary ischemia, limb ischemia, a burn, a wound, a chronic sore, or an ulceration. 
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 41  wherein the cells are administered by localized injection, systemic injection, in a patch, or on a stent. 
     
     
         47 . The method of  claim 41  wherein the effective amount of the enriched population of MPCs is administered by topical application. 
     
     
         48 - 49 . (canceled) 
     
     
         50 . The method of  claim 41 , wherein administering the enriched population of MPCs results in increased numbers of blood vessels, arterioles, capillaries and venules in the damaged tissue. 
     
     
         51 . (canceled) 
     
     
         52 . The method of  claim 41  wherein the enriched population of MPC assemble into new blood vessel structures. 
     
     
         53 . (canceled) 
     
     
         54 . The method of  claim 41 , wherein the MPCs are autologous. 
     
     
         55 . The method of  claim 41 , wherein the MPCs are allogeneic. 
     
     
         56 . The method of  claim 41  wherein the MPCs are positive for one or more of the markers STRO-1, 3G5, MUC18/CD146, alpha-smooth muscle action, or VCAM-1. 
     
     
         57 - 62 . (canceled) 
     
     
         63 . The method of  claim 56  wherein the MPCs co-express one or more of the markers selected from the group consisting of THY-1, VCAM-1, ICAM-1, PECAM-1, CD49a/CD49b/CD29, CD49c/CD29, CD49d/CD29, CD29, CD61, integrin beta5, 6-19, thrombomodulin, CDIO, CD13, SCF, PDGF-R, EGF-R, IGF-1R, NGF-R, FGF-R, and Leptin-R (STRO-2). 
     
     
         64 . The method of  claim 41  wherein the MPCs are negative for the markers CD34, CD45, and glycophorin-A. 
     
     
         65 . The method of  claim 41  wherein the enriched population comprises at least 0.01% MPCs capable of forming a clonogenic colony and differentiating to three or more mesenchymal tissue types. 
     
     
         66 . The method of  claim 41  wherein the enriched population comprises at least 0.1% MPCs capable of forming a clonogenic colony and differentiating to three or more mesenchymal tissue types. 
     
     
         67 - 70 . (canceled) 
     
     
         71 . The method  claim 41  wherein the enriched population is a population enriched from a tissue selected from the group consisting of adipose tissue, teeth, dental pulp, skin, liver, kidney, heart, retina, brain, hair follicles, intestine, lung, spleen, lymph node, thymus, pancreas, bone, ligament, bone marrow, tendon, and skeletal muscle. 
     
     
         72 . The method of  claim 41  wherein the enriched population is a culture-expanded enriched population. 
     
     
         73 . The method of  claim 72  wherein the expanded population comprises at least 0.01% MPCs capable of forming a clonogenic colony and differentiating to three or more mesenchymal tissue types. 
     
     
         74 . The method of  claim 72  wherein the expanded population comprises at least 0.1% MPCs capable of forming a clonogenic colony and differentiating to three or more mesenchymal tissue types. 
     
     
         75 . (canceled) 
     
     
         76 . The method of  claim 72  wherein the expanded population comprises at least 0.1% STRO-1 bright MPCs. 
     
     
         77 .- 89 . (canceled) 
     
     
         90 . A composition for use in repairing tissue damage comprising a population of mesenchymal precursor cells (MCPs) in a pharmaceutically acceptable carrier, said MPCs carrying a perivascular marker and being a vascular progenitor. 
     
     
         91 . (canceled) 
     
     
         92 . The composition of  claim 90  wherein the MPCs are positive for the marker STRO-1. 
     
     
         93 .- 97 . (canceled) 
     
     
         98 . The composition of  claim 92  wherein the MPC co-expresses one or more markers selected from the group consisting of THY-1, VCAM-1, ICAM-1, PECAM-1, CD49a/CD49b/CD29, CD49c/CD29, CD49d/CD29, CD29, CD61, integrin beta5, thrombomodulin, CD10, CD13, SCF, PDGF-R, EGF-R, IGF-1R, NGF-R, FGF-R, and Leptin-R (STRO-2). 
     
     
         99 . The composition of  claim 90  wherein the MPCs are negative for the markers CD34, CD45, and glycophorin-A. 
     
     
         100 .- 106 . (canceled) 
     
     
         107 . The composition of  claim 90  wherein the enriched population is a culture-expanded enriched population. 
     
     
         108 .- 110 . (canceled) 
     
     
         111 . The composition of  claim 107  wherein the expanded population comprises at least 0.1% STRO-1 bright MPCs. 
     
     
         112 - 114 . (canceled) 
     
     
         115 . The composition of  claim 90  wherein the MPCs allogeneic MPCs. 
     
     
         116 - 125 . (canceled) 
     
     
         126 . The composition of  claim 90  wherein the MPCs are genetically modified to express an exogenous gene. 
     
     
         127 - 128 . (canceled) 
     
     
         129 . The composition of  claim 90  further comprising one or more blood vessel promoting compounds. 
     
     
         130 . (canceled)