Distal Airway Stem Cells Yield Alveoli In Vitro and during Lung Regeneration following H1N1 Influenza Infection

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Cell, Volume 147, Issue 3, 525-538, 28 October 2011
Copyright ? 2011 Elsevier Inc. All rights reserved.
10.1016/j.cell.2011.10.001

Referred to by: A Breath of Fresh Air in Lung Regenerati...
Authors
Pooja A. Kumar, Yuanyu Hu, Yusuke Yamamoto, Neo Boon Hoe, Tay Seok Wei, Dakai Mu, Yan Sun, Lim Siew Joo, Rania Dagher, Elisabeth M. Zielonka, De Yun Wang, Bing Lim, Vincent T. Chow, Christopher P. Crum, Wa Xiansend email, Frank McKeonsend emailSee Affiliations

Highlights
Lung regeneration after H1N1 influenza infection involves p63-expressing DASCs
Pedigrees of cloned DASCs are intrinsically committed to form alveoli in vitro
DASCs radiate to damaged lung to form ?Krt5 pods? that mature to incipient alveoli
Expression profile of Krt5+ pods reflects dynamic intermediates in lung regeneration

Summary

The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel finding that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease.

http://www.cell.com/abstract/S0092-8674(11)01173-1

 

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Re: Distal Airway Stem Cells Yield Alveoli In Vitro and during Lung Regeneration following H1N1 Influenza Infection

Regenerated Lungs from Stem Cells Bring Possible Therapy [/SIZE

Severe cases of the flu can trash lungs, leaving patients gasping for breath.

In a first, researchers used regenerative stem cells to repair fragile damaged lungs in mice previously infected by a nasty strain of H1N1 influenza. The results could lead to new therapies for asthma, chronic bronchitis and emphysema in humans.
The research will appear in the journal Cell on Friday.

"This virus is as close as you can get to the one responsible for the 1918 influenza pandemic," said Frank McKeon of the Genome Institute of Singapore and the Harvard Medical School, who led the study. The 1918 influenza virus killed nearly eight million people, according historic reports. "You get massive lung damage, infiltration of white cells, and loss of lung tissues. Two months out, the lungs miraculously look normal again."

The team of U.S., Singapore and French researchers captured stem cells that not only regenerated lung tissues inside mice, but also generated lung-like tissue in petri dishes.

Whether the research will lead to better lung therapies has detractors, McKeon among them.



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"The problem in the case of a pandemic is that people die quickly," McKeon said. "It is hard to imagine how a cell-based treatment will play in those time constraints."

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http://www.ibtimes.com/articles/238981/20111027/h1n1-influenza-stem-cells-regenerative-lung-mice.htm