Compositions and method for manipulating pim-1 activity in circulatory system cells

Abstract

The invention provides compositions (e.g., pharmaceutical compositions) comprising nucleic acids encoding the serine/threonine kinase PIM-1, and methods for making and using them; including methods for inducing cellular proliferation, and protecting cardiac cells from hypoxia and cellular apoptosis. The invention provides compositions (e.g., pharmaceutical compositions) comprising nucleic acids encoding PIM-1, and methods for enhancing the regenerative potential of stem cells in the heart.

1 - 20 . (canceled) 
     
     
         21 . A composition for enhancing the regenerative potential of progenitor cardiac cells in a heart, the composition comprising:
 a cell population comprising, or a plurality of, isolated human cardiac progenitor cells comprising a recombinant expression vector encoding Pim-1 to overexpress Pim-1.   
     
     
         22 . The composition of  claim 21 , wherein the human cardiac progenitor cells comprise a DNA encoding human Pim-1 under control of a heterologous non-Pim-1 promoter. 
     
     
         23 . The composition of  claim 22 , wherein the promoter is a constitutive promoter. 
     
     
         24 . The composition of  claim 22 , wherein the promoter is a non-human promoter. 
     
     
         25 . The composition of  claim 21 , wherein the cell population is enriched in human cardiac progenitor cells. 
     
     
         26 . The composition of  claim 21 , wherein the composition is in a container in vitro. 
     
     
         27 . The composition of  claim 21 , wherein the composition is in a device suitable for injecting said composition into a cardiac tissue. 
     
     
         28 . The composition of  claim 21 , wherein the composition is formulated for administration to heart muscle in vivo. 
     
     
         29 . The composition of  claim 22 , wherein the DNA encoding human Pim-1 under control of a heterologous non-Pim-1 promoter is contained in a plasmid. 
     
     
         30 . The composition of  claim 22 , wherein the DNA encoding human Pim-1 under control of a heterologous non-Pim-1 promoter is contained in a recombinant virus or an artificial chromosome. 
     
     
         31 . The composition of  claim 22 , wherein the DNA encoding human Pim-1 under control of a heterologous non-Pim-1 promoter is contained in a recombinant adeno-associated viral vector; an adenovirus vector, a retroviral vector; or a lentiviral vector. 
     
     
         32 . A composition comprising:
 an isolated and genetically altered or engineered progenitor cardiac cell that overexpresses Pim-1,   wherein the altered or engineered progenitor cardiac cell is prepared by a process comprising:   (a) obtaining a cardiac tissue from a living mammalian subject;   (b) isolating from the cardiac tissue a cardiac progenitor cell capable of differentiating into a cardiomyocyte; and   (c) genetically altering or engineering an isolated cardiac progenitor cell to contain a recombinant expression vector encoding Pim-1 to overexpress Pim-1.