Adult cardiac uncommitted progenitor cells
The invention provides for adult cardiac uncommitted progenitor cells (UPCs), methods of making such cells, and methods of using such cells in the treatment, repair and/or regeneration of damaged cardiac tissue.
1 . A substantially pure population of adult cardiac uncommitted progenitor cells (UPCs), wherein said adult cardiac UPCs express the markers SSEA-1 and/or Oct-4.
2 . The adult cardiac UPCs of claim 1 , wherein said cells commit to a lineage of mesoderm cells under primary culture conditions.
3 . The adult cardiac UPCs of claim 2 , wherein said mesoderm cells express the marker flk-1 and do not express the marker CD31.
4 . The adult cardiac UPCs of claim 3 , wherein said mesoderm cells express the markers abcg-2, c-kit and sca-1.
5 . The adult cardiac UPCs of claim 3 , wherein said mesoderm cells do not express the markers VECD 1, CD45 or SSEA-4.
6 . The adult cardiac UPCs of claim 2 , wherein said mesoderm cells differentiate into cardiocyte precursor cells expressing the markers nk.x2.5, GATA-4 and/or isl-1 under differentiation culture conditions.
7 . The adult cardiac UPCs of claim 6 , wherein said cardiocyte precursor cells are ventricle cardiocyte precursor cells.
8 . The adult cardiac UPCs of claim 1 , wherein said UPCs are capable of differentiating into endothelial cells, smooth muscle cells, and cardiomyocyte cells.
9 . The adult cardiac UPCs of claim 8 , wherein said endothelial cells express the marker vWF.
10 . The adult cardiac UPCs of claim 8 , wherein said smooth muscle cells express the markers SMA and smoothelin.
11 . The adult cardiac UPCs of claim 8 , wherein said cardiomyocyte cells express the markers GATA-4 and MEF-2C.
12 . The adult cardiac UPCs of claim 1 , wherein the SSEA-1 and/or Oct-4 markers are downregulated under differentiation conditions.
13 . A method of reducing infarct size in the absence of teratoma production, comprising the steps of:
contacting an infarct region with the adult cardiac UPCs of claim 1 .
14 . The method of claim 13 , wherein said adult cardiac UPCs express the markers cardiac MHC and Cn43 following said administration.
15 . The method of claim 13 , further comprising monitoring the size of the infarct region before and after said contacting step.
16 . The method of claim 13 , further comprising monitoring ventricular function or performance, fractional shortening (FS), ejection fraction (EF), left ventricular remodeling, left ventricular end-diastolic diameter (LVEDD), and/or left ventricular end-diastolic volume (LVEDV).
17 . The method of claim 13 , wherein said method improves ventricular function or performance, increases fractional shortening (FS), increases the ejection fraction (EF), attenuates left ventricular remodeling, reduces left ventricular end-diastolic diameter (LVEDD), and/or reduces left ventricular end-diastolic volume (LVEDV).
18 . The method of claim 13 , wherein said adult cardiac UPCs are autologous to the patient that underwent said infarct.
19 . The method of claim 13 , wherein said contacting comprises injecting said cells.
20 . A method of repairing or regenerating cardiac tissue in the absence of teratoma production, comprising the steps of:
contacting cardiac tissue with the adult cardiac UPCs of claim 1.