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Collaborative Studies on Lung Stem Cell Biology and Cell Based Therapy

Edward Ingenito, MD, Ph.D
Brigham and Women’s Hospital

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Dr. Edward Ingenito is an Assistant Professor of Medicine at Harvard Medical School and an Associate Physician at Brigham and Women’s Hospital.

He received his medical degree from Harvard Medical School.

Consortium Research Title: Pneumografting- A Novel Cell-Based Therapy for Emphysema

Consortium Research Description:

Recent studies suggest that reparative cells which contribute to healing in the lung following injury also possess regenerative capacity. Although the biology of post-natal lung regeneration is not well understood, mechanical pre-stress appears to be an absolute requirement for tissue regeneration to occur. Emphysema, a disease characterized by tissue destruction, is a potential target for cell-based therapy. This disease is associated with: 1) loss of resident reparative cells; 2) loss of the extracellular matrix that transmits pre-stress signaling; 3) and loss of pre-stress itself, the very signal required to trigger regenerative responses. Although these factors represent obstacles to the development of regenerative therapeutic strategies for emphysema, preliminary studies in our lab show that modulation of mesenchymal and epithelial cell proliferation using members of the fibroblast growth factor family complexed to carrier molecules in a biocompatible polymer can promote expansion of parenchymal tissues. The polymer scaffold, an air containing foam with mechanical properties similar to healthy lung tissue, effectively transmits stress to reparative/progenitor cells to promote proliferation and remodeling. Studies proposed here will test the hypothesis that 1) therapeutic post-natal lung tissue growth in emphysema can be achieved by augmenting the lung's innate healing response using growth factors to direct endogenous reparative lung cells following a localized mild injury; and that 2) the magnitude of this response can be modulated by altering pre-stress using concomitant bronchoscopic lung volume reduction therapy to increase transpulmonary pressures. We intend to advance this approach, known as pneumografting, into human trials under a physician-sponsored Investigation New Drug Application.

Ingenito Lab Information: 
75 Francis St., Boston, MA 02115

Recent Publications

  • Ingenito EP, Sen E, Tsai LW, Murthy S, Hoffman A. Design and testing of biological scaffolds for delivering reparative cells to target sites in the lung. J Tissue Eng Regen Med. 2009 Dec 17. [Epub ahead of print]
  • Hoffman AM, Shifren A, Mazan MR, Gruntman AM, Lascola KM, Nolen-Walston RD, Kim CF, Tsai L, Pierce RA, Mecham RP, Ingenito EP. Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in mice. Am J Physiol Lung Cell Mol Physiol. 2010 Feb; 298(2):L158-68. Epub 2009 Nov 13.
  • Paxson, Julia A; Parkin, Christopher D; Iyer, Lakshmanan K; Mazan, Melissa R; Ingenito, Edward P; Hoffman, Andrew M. Global gene expression patterns in the post-pneumonectomy lung of adult mice. Respiratory Research. 2009; 10 :92