Endothelial progenitor cells and methods of use thereof
Endothelial progenitor cells immunoreactive for VEGFR-2 or Tie-2, and CD45 are provided. Optionally the cell is immunoreactive with CD14. The cells are capable of differentiating in vivo into an endothelial cell or a smooth muscle cells. The cultures integrate well after transplantation into adult vasculature.
1 . An in vitro cell culture comprising cells derived from peripheral blood of a human, wherein said cells in the culture are
a. Tie-2 + or VEGFR-2 + ;
b. CD144 − and CD45 + ;
c. capable of cultivation in a culture; and
d. capable of proliferating and differentiating in vivo into endothelial cells and smooth muscle cells.
2 . The culture of claim 1 , wherein the cells in the culture are viable at least 2 weeks.
3 . The culture of claim 1 , wherein the cells in the culture are viable at least 4 weeks.
4 . The culture of claim 1 , wherein said culture is an adhesion culture.
5 . A method of producing a population of human progenitor cells which differentiate in vivo into endothelial cells or smooth muscle cells, comprising selecting from a population of human peripheral blood derived cells for cells that are CD144 − , CD45 + and Tie-2 + or VEGFR-2 +.
6 . A method transplanting multipotent progenitor cells into a subject comprising
a. providing an in vitro cell culture comprising multipotential human CD144 − , CD45 + and Tie-2 + or VEGFR-2 + progenitor cells wherein said cells maintain multipotential capacity to differentiate in vivo into endothelial cells or smooth muscle cells; and
b. transplanting said cells in said subject.
7 . The method of claim 6 , where is said subject suffers from a vascular disorder.
8 . A method of repopulating an injured blood vessel in a subject comprising administering to a subject a composition comprising a population of multipotential human CD144 − , CD45 + and Tie-2 + or VEGFR-2 + progenitor cells wherein said cells maintain multipotential capacity to differentiate in vivo into endothelial cells or smooth muscle cells.
9 . The method of claim 8 , wherein said composition is administered directly to the blood vessel.
10 . The method of claim 8 , wherein said composition is administered directly to an arterial bed.
11 . The method of claim 8 , wherein said blood vessel is a vein or an artery.
12 . The method of claim 8 , wherein said subject suffers from a vascular disorder.
13 . A method of endothelizing a vascular graft, comprising contacting said vascular graft with a composition comprising a population of multipotential human CD144 − , CD45 + and Tie-2 + or VEGFR-2 + progenitor cells wherein said cells maintain multipotential capacity to differentiate in vivo into endothelial cells or smooth muscle cells.
14 . The method of claim 13 , wherein said graft is an artificial vascular graft.
15 . The method of claim 13 , wherein said graft is an allograft.
16 . The method of claim 13 , wherein said graft is an isograft.
17 . The method of claim 13 , wherein said vascular graft is contacted in vitro, in vivo or ex vivo.
18 . The method of claim 13 , wherein said vascular graft is contacted with said composition prior to implantation into a subject.
19 . The method of claim 13 , wherein said vascular graft is contacted with said composition after implantation into a subject.
20 . The method of claim 13 , wherein said vascular graft is a vein or an artery.
21 . An in vitro cell culture comprising cells derived from peripheral blood of a human, wherein said cells in the culture are
a. VEGFR-2 + ; CD14 + , CD144 − and CD45 + ;
b. capable of cultivation in a culture; and
c. capable of proliferating and differentiating in vivo into endothelial cells.
22 . The culture of claim 21 , wherein the cells in the culture are viable at least 2 weeks.
23 . The culture of claim 21 , wherein the cells in the culture are viable at least 4 weeks.
24 . The culture of claim 21 , wherein said culture is an adhesion culture.
25 . A method of producing a population of human progenitor cells which differentiate in vivo into endothelial cells, comprising selecting from a population of human peripheral blood derived cells for cells that are CD144 − , CD45 + , CD14 + and VEGFR-2+.
26 . A method transplanting progenitor cell into a subject comprising
a. providing an in vitro cell culture comprising human CD144 − , CD45 + , CD14 + and VEGFR-2 + progenitor cells wherein said cells maintain capacity to differentiate in vivo into endothelial cells; and
b. transplanting said cells in said subject.
27 . The method of claim 26 , where is said subject suffers from a vascular disorder.
28 . A method of repopulating an injured blood vessel in a subject comprising administering to a subject a composition comprising a population of human CD144 31 , CD45 + , CD14 + and VEGFR-2 + progenitor cells wherein said cells maintain the capacity to differentiate in vivo into endothelial cells.
29 . The method of claim 28 , wherein said composition is administered directly to the blood vessel.
30 . The method of claim 28 , wherein said composition is administered directly to an arterial bed.
31 . The method of claim 28 , wherein said blood vessel is a vein or an artery.
32 . The method of claim 28 , wherein said subject suffers from a vascular disorder.
33 . A method of endothelizing a vascular graft, comprising contacting said vascular graft with a composition comprising a population of multipotential human CD144 − , CD45 + , CD14 + and VEGFR-2 + progenitor cells wherein said cells maintain the capacity to differentiate in vivo into endothelial cells.
34 . The method of claim 33 , wherein said graft is an artificial vascular graft.
35 . The method of claim 33 , wherein said graft is an allograft.
36 . The method of claim 33 , wherein said graft is an isograft.
37 . The method of claim 33 , wherein said vascular graft is contacted in vitro, in vivo or ex vivo.
38 . The method of claim 33 , wherein said vascular graft is contacted with said composition prior to implantation into a subject.
39 . The method of claim 33 , wherein said vascular graft is contacted with said composition after implantation into a subject.
40 . The method of claim 33 , wherein said vascular graft is a vein or an artery.