Perivascular mesenchymal precursor cell induced blood vessel formation
View Patent ↗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 neovascularization 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. A method of inducing formation or repair of blood vessels in an ischemic first tissue, comprising contacting the ischemic first tissue with a population of cells which has been enriched for mesenchymal precursor cells (MPCs) that express the markers STRO-1, CD146, and alpha smooth muscle actin but are negative for CD34, CD45, and glycophorin A, so as to thereby induce formation of blood vessels or repair of existing blood vessels in the ischemic first tissue.
2. The method of claim 1 wherein the population of cells comprises at least 0.01% MPCs capable of forming a clonogenic colony.
3. The method of claim 1 wherein the population of cells comprises at least 0.1% MPCs capable of forming a clonogenic colony.
4. The method of claim 1 wherein the population of cells comprises at least 0.01% STRO-1 bright MPCs.
5. The method of claim 1 wherein the population of cells comprises at least 0.1% STRO-1 bright MPCs.
6. The method of claim 1 wherein the population of cells comprises at least 1% STRO-1 bright MPCs.
7. The method of claim 1 wherein the MPCs that express the marker STRO-1 additionally co-express the marker VCAM-1.
8. The method of claim 1 wherein the population of cells is derived from a second tissue selected from the group consisting of skin, liver, kidney, heart, adipose tissue, teeth, dental pulp, retina, brain, hair follicles, intestine, lung, spleen, lymph node, thymus, pancreas, bone, ligament, bone marrow, tendon, and skeletal muscle.
9. The method of claim 1 wherein the population of cells is isolated from a perivascular niche within a vascularised tissue source.
10. The method of claim 1 wherein the population of cells is isolated from a perivascular niche within a non-haemopoietic vascularised tissue.
11. The method of claim 1 wherein the population of cells comprises at least 10% STRO-1 bright MPCs.
12. The method claim 1 wherein the MPCs that express the marker STRO-1 co-express any 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, CD10, CD13, SCF, PDGF-R, EGF-R, IGF-1R, NGF-R, FGF-R and Leptin-R (STRO-2).
13. A method of inducing neovascularisation in a target ischemic tissue of a patient, the method comprising the step of administering to the target ischemic tissue an effective amount of a population of human mesenchymal precursor cells (MPCs) which has been enriched for cells that express the markers STRO-1, CD146, and alpha smooth muscle actin but are negative for CD34, CD45, and glycophorin A.
14. The method according to claim 12 , wherein the target tissue is cardiac tissue.
15. The method of claim 1 , wherein the ischemic tissue is in a subject suffering from cerebrovascular ischemia, renal ischemia, pulmonary ischemia, limb ischemia, ischemic cardiomyopathy, or myocardial ischemia.
16. The method of claim 1 , wherein the MPCs that express the marker STRO-1 are human.
17. The method of claim 1 , further comprising seeding the purified populations of human cells in a matrix prior to contacting the first tissue.
18. The method of claim 17 , wherein the matrix is a scaffold.
19. The method of claim 18 , wherein the scaffold induces differentiation of the population of human cells.
20. The method of claim 1 , further comprising contacting the ischemic first tissue with a compound known to promote formation or repair of blood vessels.
21. The method of claim 13 , wherein the population of cells comprises at least 0.01% MPCs capable of forming a clonogenic colony.
22. The method of claim 13 , wherein the population of cells comprises at least 0.1% MPCs capable of forming a clonogenic colony.
23. The method of claim 21 , wherein the population of cells comprises at least 0.01% STRO-1 bright MPCs.
24. The method of claim 22 , wherein the population of cells comprises at least 0.1% STRO-1 bright MPCs.
25. The method of claim 13 , wherein the population of cells comprises at least 1% STRO-1 bright MPCs.
26. The method of claim 25 , wherein the MPCs that express the marker STRO-1 additionally co-express the marker VCAM-1.
27. The method of claim 25 , wherein the population of cells is derived from a second tissue of the patient selected from the group consisting of skin, liver, kidney, heart, adipose tissue, teeth, dental pulp, retina, brain, hair follicles, intestine, lung, spleen, lymph node, thymus, pancreas, bone, ligament, tendon, and skeletal muscle.
28. The method of claim 25 , wherein the population of cells is isolated from a perivascular niche within a vascularised tissue source.
29. The method of claim 25 , wherein the population of cells is isolated from a perivascular niche within a non-haemopoietic vascularised tissue.
30. The method of claim 25 , further comprising seeding the population of human cells in a matrix prior to contacting the first tissue.
31. The method of claim 30 , wherein the matrix is a scaffold.
32. The method of claim 31 , wherein the scaffold induces differentiation of the population of human cells.
33. The method of claim 25 , further comprising administering to the patient a compound known to promote formation or repair of blood vessels.
34. The method of claim 33 , wherein the population of human MPCs and the compound known to promote formation or repair of blood vessels are coadministered.
35. The method of claim 1 , wherein the enriched population is cultured and/or expanded prior to contacting the ischemic first tissue.
36. The method of claim 13 , wherein the enriched population is cultured and/or expanded prior to contacting the ischemic first tissue.