Human Lung Stem Cells?

Recently, Dr. Piero Anversa of Brigham and Women’s reported identification of human lung stem cells, appeared in May 12, 2011, issue of New England Journal of Medicine. The flow cytometric identification was based on c-kit antigen. The authors showed that the stem cells isolated were clonal and pluripotent. c-kit+ cells expressed KLF4, nanog,, oct4, and sox2. In a cryo injury mouse model, the authors showed that c-kit+  cells were, amazingly, able to promote lung regeneration!

In an editorial, Dr. Chapman of UCSF stated that "Kajstura et al. resets the starting point for clinical investigation into the role of stem cells and progenitor cells in lung disease". 

However, several scientists in the field were more skeptical. In Nature Medicine Community Corner, Dr. Stripp and Dr. Hogan of Duke questioned the experimental methodology (eg, RT-PCR and antibody staining) and proper controls.  They urged that more vigorous validation is needed. More importantly, the c-kit-CreER mice is needed to trace if the c-kit+ cells in the LUNG are pluripotent, hierarchical differentiation. Dr. Thannickal of UAB also suggested “The phenotype and fate of endogenous lung stem cells and associated alterations of their tissue niche in disease states will need to be characterized.” He also questioned if there is any deficiency in c-kit+ cells in COPD or IPF. In a reply, Dr. Anversa sounded very angry implying that the comments by Drs. Hogan and Stripp were "border on personal attacks".

Dr. Anversa's early work "Bone marrow cells regenerate infarcted myocardium" published in Nature 2001, stated that Lin- c-kit+ bone marrow cells were able to generate myocardium de novo. Dr. Weissman demonstrated that BM hematopoietic stem cells (KTLS) robustly reconstituted peripheral blood leukocytes, but did not contribute appreciably to any nonhematopoietic tissues, indicating that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all. 

References

Kajstura J, Rota M, Hall SR, Hosoda T, D'Amario D, Sanada F, Zheng H, Ogórek B, Rondon-Clavo C, Ferreira-Martins J, Matsuda A, Arranto C, Goichberg P, Giordano G, Haley KJ, Bardelli S, Rayatzadeh H, Liu X, Quaini F, Liao R, Leri A, Perrella MA, Loscalzo J, Anversa P. Evidence for human lung stem cells. N Engl J Med. 2011 May 12;364(19):1795-806. PubMed PMID: 21561345.

Chapman HA. Toward lung regeneration. N Engl J Med. 2011 May
12;364(19):1867-8. PubMed PMID: 21561353.

Hogan, B., Stripp, B. & Thannickal, V.J. Lung stem cells: looking beyond the hype. Nat Med. 2011 Jul 7;17(7):788-9. doi: 10.1038/nm0711-788. PubMed PMID: 21738157.

Anversa P, Kajstura J, Leri A, Loscalzo J. Tissue-specific adult stem cells in the human lung. Nat Med. 2011 Sep 7;17(9):1038-9. doi: 10.1038/nm.2463. PubMed PMID: 21900912.

Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J,
McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature. 2001 Apr 5;410(6829):701-5. PubMed PMID:11287958. 

Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002 Sep 27;297(5590):2256-9. Epub 2002 Sep 5. PubMed PMID: 12215650.