• 1 東南大學(xué)醫(yī)學(xué)院( 江蘇南京 210009);;
  • 2 東南大學(xué)附屬中大醫(yī)院( 江蘇南京 210009) 通訊作者: 邱海波, E-mail: haiboq2000@ yahoo. com. cn;

ARDS 是引起重癥患者呼吸衰竭的主要原因, 盡管醫(yī)療技術(shù)有了很大的進步, 但對ARDS 的治療只局限在器官支持層面, 其病死率仍高達40% [ 1] 。ARDS的主要病理改變?yōu)榉闻萆掀ぜ毎兔氀軆?nèi)皮細胞受損, 通透性增加, 富含蛋白質(zhì)的液體滲出積聚于肺間質(zhì)和肺泡。因此促進損傷肺毛細血管內(nèi)皮細胞和肺泡上皮細胞的有效修復(fù)可能是ARDS治療的關(guān)鍵所在。隨著干細胞工程學(xué)的發(fā)展, 間充質(zhì)干細胞( MSC) 作為一種理想的組織修復(fù)來源, 在ARDS 治療中的應(yīng)用受到越來越多的關(guān)注, 這可能為ARDS 的治療開辟一條新的途徑。

引用本文： 劉艾然 ,邱海波. 間充質(zhì)干細胞在ALI /ARDS中應(yīng)用的研究進展. 中國呼吸與危重監(jiān)護雜志, 2010, 9(3): 332-335. doi: 復(fù)制

1. Rubenfeld GD，Caldwell E，Peabody E，et al.Incidence and outcomes of acute lung injury.N Engl J Med，2005，353：1685-1693.
2. Dominici M，Le Blanc K，Mueller I，et al.Minimal criteria for defining multipotent mesenchymal stromal cells.The International Society for Cellular Therapy position statement.Cytotherapy，2006，8：315-317.
3. da Silva Meirelles L，Chagastelles PC，Nardi NB.Mesenchymal stem cells reside in virtually all post-natal organs and tissues.J Cell Sci，2006，119：2204-2213.
4. Lama VN，Smith L，Badri L，et al.Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts.J Clin Invest，2007，117：989-996.
5. Kubo H，Hegab AE，He M，et al.Endogenous lung stem cells increased after lung injury.Proc Am Thorac Soc，2008，5：362-363.
6. Rojas M，Xu J，Woods CR，et al.Bone marrow-derived mesenchymal stem cells in repair of the injured lung.Am J Respir Cell Mol Biol，2005，33：145-152.
7. Gupta N，Su X，Popov B，et al.Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice.J Immunol，2007，179：1855-1863.
8. Ortiz LA，Gambelli F，Mcbride C，et al.Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects.Proc Natl Acad Sci USA，2003，100：8407-8411.
9. Zhao F，Zhang YF，Liu YG，et al.Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats.Transplant Proc，2008，40：1700-1705.
10. Lee JW，F(xiàn)ang X，Gupta N，et al.Allogeneic human mesenchymal stem cells for treatment of E.coli endotoxin-induced acute lung injury in the ex vivo perfused human lung.Proc Natl Acad Sci USA，2009，106：16357-16362.
11. Wang Y，Johnsen HE，Mortensen S，et al.Changes in circulating mesenchymal stem cells，stem cell homing factor，and vascular growth factors in patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.Heart，2006，92：768-774.
12. Xu J，Woods CR，Mora AL，et al.Role of the SDF-1/CXCR4 axis in the pathogenesis of lung injury and ?brosis.Am J Respir Cell Mol Biol，2007，37：291-299.
13. Cho HJ，Kim HS，Lee MM，et al.Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation.Circulation，2003，108：2918-2925.
14. Hashimoto N，H Jin，T Liu，et al.Bone marrow-derived progenitor cells in pulmonary ?brosis.J Clin Invest，2004，113：243-252.
15. Moore BB，Kolodsick JE，Thannickal VJ，et al.CCR2-mediated recruitment of ?brocytes to the alveolar space after ?brotic injury.Am J Pathol，2005，166：675-684.
16. Rojas M，Xu J，Woods CR，et al.Bone marrow-derived mesenchymal stem cells in repair of the injured lung.Am J Respir Cell Mol Biol，2005，33：145-152.
17. Serikov VB，Popov B，Mikhailov VM，et al.Evidence of temporary airway epithelial repopulation and rare clonal formation by BM-derived cells following naphthalene injury in mice.Anat Rec （Hoboken），2007，290：1033-1045.
18. Mei SH，McCarter SD，Deng Y，et al.Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med，2007，4：e269.
19. Maccario R，Podesta M，Moretta A et al.Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T2 cell subsets expressing a regulatory/ suppressive phenotype.Haematologica，2005，90：516-525.
20. Xu J，Woods CR，Mora AL，et al.Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice.Am J Physiol Lung Cell Mol Physiol，2007，293：131-141.
21. Németh K，Leelahavanichkul A，Yuen PST，et al.Bone marrow stromal cells attenuate sepsis via prostaglandin E2—dependent reprogramming of host macrophages to increase their interleukin-10 production.Nat Med，2009，15：42-49.
22. Ortiz LA，Dutreil M，F(xiàn)attman C，et al.Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury.Proc Natl Acad Sci U S A. PNAS，2007，104：11002-11007.
23. Ware LB，Matthay MA.Alveolar ?uid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome.AmJ Respir Crit Care Med，2001，163：1376-1383.
24. Dagenais A，F(xiàn)réchette R，Yamagata Y，et al.Down regulation of ENaC activity and expression by TNF-α in alveolar epithelial cells.Am J Physiol Lung Cell Mol Physiol，2004，286：301-311.
25. Lee JW，Gupta N，Serikov V，et al.Potential application of mesenchymal stem cells in acute lung injury.Expert Opin Biol Ther，2009，9：1259-1270.
26. MurakamiM，Nguyen LT，Zhang ZW，et al.The FGF systemhas a key role in regulating vascular integrity.J Clin Invest，2008，118：3355-3366.
27. Liu XL，Sato S，Dai W，et al.The protective effect of hepatocye growth-promoting factor （pHGF） against hydrogen peroxide-induce acute lung in rats.Med Electron Microsc，2001，34：92-102.
28. 徐金富，瞿介明，宋琳，等.高表達促血管生成素1間充質(zhì)干細胞的構(gòu)建及其在肺損傷中的應(yīng)用.中國呼吸與危重監(jiān)護雜志，2009，8：575-579.
29. Leblond AL，Naud P，F(xiàn)orest V，et al.Developing cell therapy techniques for respiratory disease：intratracheal dDelivery of genetically engineered stem cells in a murine model of airway injury.Hum Gene Ther，2009，20：1329-1343.
30. Tolar J，Nauta AJ，Osborn MJ，et al.Sarcoma derived from cultured mesenchymal stem cells.Stem Cells，2007，25：371-379.
31. Corcoran KE，Trzaska KA，F(xiàn)ernandes H，et al.Mesenchymal stem cells in early entry of breast cancer into bone marrow.PLoS One，2008，3：e2563.
32. Epperly MW，Guo H，Gretton JE，et al.Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis.Am J Respir Cell Mol Biol，2003，29：213-224.
33. Yan X，Liu Y，Han Q，et al.Injured microenvironment directly guides the differentiation of engrafted Flk-1（+） mesenchymal stem cell in lung.Exp Hematol，2007，35：1466-1475.
  1. 1. Rubenfeld GD，Caldwell E，Peabody E，et al.Incidence and outcomes of acute lung injury.N Engl J Med，2005，353：1685-1693.
  2. 2. Dominici M，Le Blanc K，Mueller I，et al.Minimal criteria for defining multipotent mesenchymal stromal cells.The International Society for Cellular Therapy position statement.Cytotherapy，2006，8：315-317.
  3. 3. da Silva Meirelles L，Chagastelles PC，Nardi NB.Mesenchymal stem cells reside in virtually all post-natal organs and tissues.J Cell Sci，2006，119：2204-2213.
  4. 4. Lama VN，Smith L，Badri L，et al.Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts.J Clin Invest，2007，117：989-996.
  5. 5. Kubo H，Hegab AE，He M，et al.Endogenous lung stem cells increased after lung injury.Proc Am Thorac Soc，2008，5：362-363.
  6. 6. Rojas M，Xu J，Woods CR，et al.Bone marrow-derived mesenchymal stem cells in repair of the injured lung.Am J Respir Cell Mol Biol，2005，33：145-152.
  7. 7. Gupta N，Su X，Popov B，et al.Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice.J Immunol，2007，179：1855-1863.
  8. 8. Ortiz LA，Gambelli F，Mcbride C，et al.Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects.Proc Natl Acad Sci USA，2003，100：8407-8411.
  9. 9. Zhao F，Zhang YF，Liu YG，et al.Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats.Transplant Proc，2008，40：1700-1705.
  10. 10. Lee JW，F(xiàn)ang X，Gupta N，et al.Allogeneic human mesenchymal stem cells for treatment of E.coli endotoxin-induced acute lung injury in the ex vivo perfused human lung.Proc Natl Acad Sci USA，2009，106：16357-16362.
  11. 11. Wang Y，Johnsen HE，Mortensen S，et al.Changes in circulating mesenchymal stem cells，stem cell homing factor，and vascular growth factors in patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.Heart，2006，92：768-774.
  12. 12. Xu J，Woods CR，Mora AL，et al.Role of the SDF-1/CXCR4 axis in the pathogenesis of lung injury and ?brosis.Am J Respir Cell Mol Biol，2007，37：291-299.
  13. 13. Cho HJ，Kim HS，Lee MM，et al.Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation.Circulation，2003，108：2918-2925.
  14. 14. Hashimoto N，H Jin，T Liu，et al.Bone marrow-derived progenitor cells in pulmonary ?brosis.J Clin Invest，2004，113：243-252.
  15. 15. Moore BB，Kolodsick JE，Thannickal VJ，et al.CCR2-mediated recruitment of ?brocytes to the alveolar space after ?brotic injury.Am J Pathol，2005，166：675-684.
  16. 16. Rojas M，Xu J，Woods CR，et al.Bone marrow-derived mesenchymal stem cells in repair of the injured lung.Am J Respir Cell Mol Biol，2005，33：145-152.
  17. 17. Serikov VB，Popov B，Mikhailov VM，et al.Evidence of temporary airway epithelial repopulation and rare clonal formation by BM-derived cells following naphthalene injury in mice.Anat Rec （Hoboken），2007，290：1033-1045.
  18. 18. Mei SH，McCarter SD，Deng Y，et al.Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med，2007，4：e269.
  19. 19. Maccario R，Podesta M，Moretta A et al.Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T2 cell subsets expressing a regulatory/ suppressive phenotype.Haematologica，2005，90：516-525.
  20. 20. Xu J，Woods CR，Mora AL，et al.Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice.Am J Physiol Lung Cell Mol Physiol，2007，293：131-141.
  21. 21. Németh K，Leelahavanichkul A，Yuen PST，et al.Bone marrow stromal cells attenuate sepsis via prostaglandin E2—dependent reprogramming of host macrophages to increase their interleukin-10 production.Nat Med，2009，15：42-49.
  22. 22. Ortiz LA，Dutreil M，F(xiàn)attman C，et al.Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury.Proc Natl Acad Sci U S A. PNAS，2007，104：11002-11007.
  23. 23. Ware LB，Matthay MA.Alveolar ?uid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome.AmJ Respir Crit Care Med，2001，163：1376-1383.
  24. 24. Dagenais A，F(xiàn)réchette R，Yamagata Y，et al.Down regulation of ENaC activity and expression by TNF-α in alveolar epithelial cells.Am J Physiol Lung Cell Mol Physiol，2004，286：301-311.
  25. 25. Lee JW，Gupta N，Serikov V，et al.Potential application of mesenchymal stem cells in acute lung injury.Expert Opin Biol Ther，2009，9：1259-1270.
  26. 26. MurakamiM，Nguyen LT，Zhang ZW，et al.The FGF systemhas a key role in regulating vascular integrity.J Clin Invest，2008，118：3355-3366.
  27. 27. Liu XL，Sato S，Dai W，et al.The protective effect of hepatocye growth-promoting factor （pHGF） against hydrogen peroxide-induce acute lung in rats.Med Electron Microsc，2001，34：92-102.
  28. 28. 徐金富，瞿介明，宋琳，等.高表達促血管生成素1間充質(zhì)干細胞的構(gòu)建及其在肺損傷中的應(yīng)用.中國呼吸與危重監(jiān)護雜志，2009，8：575-579.
  29. 29. Leblond AL，Naud P，F(xiàn)orest V，et al.Developing cell therapy techniques for respiratory disease：intratracheal dDelivery of genetically engineered stem cells in a murine model of airway injury.Hum Gene Ther，2009，20：1329-1343.
  30. 30. Tolar J，Nauta AJ，Osborn MJ，et al.Sarcoma derived from cultured mesenchymal stem cells.Stem Cells，2007，25：371-379.
  31. 31. Corcoran KE，Trzaska KA，F(xiàn)ernandes H，et al.Mesenchymal stem cells in early entry of breast cancer into bone marrow.PLoS One，2008，3：e2563.
  32. 32. Epperly MW，Guo H，Gretton JE，et al.Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis.Am J Respir Cell Mol Biol，2003，29：213-224.
  33. 33. Yan X，Liu Y，Han Q，et al.Injured microenvironment directly guides the differentiation of engrafted Flk-1（+） mesenchymal stem cell in lung.Exp Hematol，2007，35：1466-1475.