Treatment of lung and pulmonary diseases and disorders
Compositions and methods of using cells derived from umbilical cord tissue to stimulate and support lung tissue angiogenesis, to improve blood flow to lung tissue, to regenerate, repair, and improve lung tissue damaged by lung disease, disorder and/or injury, and to protect lung tissue from damage caused by lung disease, disorder and/or injury in a patient.
1. A method of reducing vascular leak, edema, or inflammation in a lung of a patient having hyperoxia or acute lung injury comprising systemically administering to the patient an effective amount of umbilical cord tissue-derived cells, wherein the umbilical cord tissue-derived cells are isolated from human umbilical cord tissue substantially free of blood, are capable of self-renewal and expansion in culture, have the potential to differentiate into cells of at least a lung tissue, and do not express CD117, hTERT or telomerase, and
wherein the levels of keratinocyte factor, gamma interferon-inducible cytokine, interleukin 1-alpha and monocyte chemotactic factor-1 are reduced in the lung of the patient having hyperoxia or acute lung injury.
2. The method of claim 1 , wherein the cells are induced in vitro to differentiate into a lung tissue.
3. The method of claim 1 , wherein the cells are administered with at least one other cell type.
4. The method of claim 3 , wherein the other cell type is a lung tissue cell selected from the group consisting of lung progenitor cell, vascular smooth muscle cell, vascular smooth muscle progenitor cell, pericyte, vascular endothelial cell, vascular endothelium progenitor cell, and other multipotent or pluripotent stem cell.
5. The method of claim 1 , wherein the cells are administered with at least one other agent.
6. The method of claim 5 , wherein the agent is selected from the group consisting of an antithrombogenic agent, an anti-inflammatory agent, an immunosuppressive agent, an immunomodulatory agent, a pro-angiogenic agent, and an antiapoptotic agent.
7. The method of claim 1 , wherein the umbilical cord tissue-derived cells are administered by injection, infusion, a device implanted in the patient, or by implantation of a matrix or scaffold containing the cells.
8. The method of claim 1 , wherein the cells exert a trophic effect on the lung tissue of the patient.
9. The method of claim 1 , wherein the cells exert a trophic effect on the vascular smooth muscle of the patient.
10. The method of claim 9 , wherein the trophic effect is proliferation of the vascular smooth muscle cells.
11. The method of claim 1 , wherein the cells exert a trophic effect on the vascular endothelium of the patient.
12. The method of claim 11 , wherein the trophic effect is proliferation of the vascular endothelial cells.
13. The method of claim 1 , wherein the cells induce migration of vascular endothelial cells to the sites of the lung disease, disorder or injury.
14. The method of claim 1 , wherein the cells induce migration of vascular endothelium progenitor cells to the sites of the lung disease, disorder or injury.
15. The method of claim 1 , wherein the cells induce migration of vascular smooth muscle cells to the sites of the lung disease, disorder or injury.
16. The method of claim 1 , wherein the cells induce migration of vascular smooth muscle progenitor cells to the sites of the lung disease, disorder or injury.
17. The method of claim 1 , wherein the cells induce migration of pericytes to the sites of the lung disease, disorder or injury.
18. The method of claim 1 , wherein the cells further comprise the following characteristics:
increased expression for a gene encoding interleukin 8 or reticulon 1, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell;
express CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B,C; and
do not express CD31, CD34, CD45, CD80, CD86, CD141, CD178, B7-H2, HLA-G and HLA-DR,DP,DQ.
19. The method of claim 1 , wherein the method reduces edema.
20. The method of claim 1 , wherein the method reduces vascular leak.
21. A method of reducing vascular leak, edema, or inflammation in a lung of a patient having hyperoxia or acute lung injury comprising administering umbilical cord tissue-derived cells to the patient, wherein the umbilical cord tissue-derived cells are isolated from human umbilical cord tissue substantially free of blood, are capable of self-renewal and expansion in culture, have the potential to differentiate into cells of at least a lung tissue, and do not express CD117, hTERT or telomerase, wherein the cells exert a trophic effect on the lung tissue of the patient, and wherein the levels of keratinocyte factor, gamma interferon-inducible cytokine, interleukin 1-alpha and monocyte chemotactic factor-1 are reduced in the lung of the patient having hyperoxia or acute lung injury.
22. The method of claim 21 , wherein the method reduces vascular leak.
23. The method of claim 21 , wherein the method reduces edema.
24. The method of claim 21 , wherein the cells further comprise the following characteristics:
increased expression for a gene encoding interleukin 8 or reticulon 1, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell;
express CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A,B,C; and
do not express CD31, CD34, CD45, CD80, CD86, CD141, CD178, B7-H2, HLA-G and HLA-G, DR,DP,DQ.
25. The method of claim 1 , wherein the cells are allogeneic.
26. The method of claim 21 , wherein the cells are allogeneic.
27. The method of claim 1 , wherein the patient has hyperoxia.
28. The method of claim 1 , wherein the patient has acute lung injury.
29. The method of claim 21 , wherein the patient has hyperoxia.
30. The method of claim 21 , wherein the patient has acute lung injury.
31. The method of claim 1 , wherein the method reduces inflammation in a lung of the patient having hyperoxia or acute lung injury.
32. The method of claim 21 , wherein the method reduces inflammation in a lung of the patient having hyperoxia or acute lung injury.