In Lung Research, Embryonic Stem Cells Again Play Catch-Up with Adult Stem Cells

Date: 09/12/2003

According to recent Australian media reports, scientists there have made a “revolutionary breakthrough” by coaxing embryonic stem cells to become cells that “resemble” lung cells. The reports say this is a major step forward in developing cures for numerous lung diseases, cystic fibrosis in particular.

But while these results have yet to be published in a peer-reviewed journal, peer reviewed studies do exist showing the promising use of adult stem cells to treat lung diseases …not just in a lab dish, but in actual animal models of lung damage and disease, and in actual human patients. Once again, it appears that a development hailed in the popular media as a major medical advance using embryonic stem cells, is one that actually lags well behind advances already achieved using adult stem cells.

Beneath all the rhetorical claims, there seems to be no evidence that the researchers achieved anything more than to get embryonic stem cells in a dish to resemble lung cells; no evidence is offered that the cells actually function as lung cells, or that they can repair any damage in an animal, let alone a human.

In the case of cystic fibrosis, simply replacing some lung cells with lung-like human embryonic stem cells will not alleviate the disease, because cystic fibrosis is a genetic disease. Lung epithelium turns over rapidly, so even if the lung-like cells could successfully be transplanted, they would soon die off without treating the underlying genetic disorder. Genetic engineering would be necessary to address the underlying cause of the disease.

In contrast, adult stem cells have already demonstrated the ability to bring in genetically engineered cells that could treat the underlying disease. Overall, at least four studies have already shown the use of adult stem cells to form new functioning lung tissue in animal models and in human patients:

  • J.E Grove, C. Lutzko, J. Priller, O. Henegariu, N.D. Theise, D.B. Kohn, D.S. Krause; “Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium” Am J Respir Cell Mol Bio l. 27, 645-651; Dec 2002.
  • This study showed that up to 20% of lung epithelium can be derived from bone marrow stem cells after lung injury, and that these adult stem cells can effectively deliver gene therapy to the lung while retaining the ability to differentiate into lung cells.
  • N.D. Theise, O. Henegariu, J.Grove, J. Jagirdar, P.N Kao, J.M. Crawford, S.Badve, R. Saxena, D.S. Krause “Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow” Exp Hematol. 30, 1333-1338; Nov 2002, showing that a large portion of lung damage can be repaired using bone marrow stem cells, including formation of entire alveoli (the small sacs that provide for oxygen absorption in the lungs.)
  • D.N. Kotton, B.Y. Ma, W.V.Cardoso, E.A. Sanderson, R.S.Summer, M.C. Williams, A. Fine “Bone marrow-derived cells as progenitors of lung alveolar epithelium” Development 128, 5181-5188; Dec 2001 showing that after lung injury, bone marrow stem cells injected intravenously can find their way to the lung and repair lung damage.
  • B.T. Suratt, C.D. Cool, A.E. Serls, L. Chen, M. Varella-Garcia, E.J. Shpall, K.K. Brown, G.S. Worthen; “Human pulmonary chimerism after hematopoietic stem cell transplantation”, Am. J. Respir. Crit. Care Med. 168, 318–322, 2003 (published online April 30, 2003) which showed that bone marrow stem cells can form lung tissue in human patients. Patients who had bone marrow stem cell transplantations showed up to 8% of differentiated lung cells and up to 42% of lung blood vessels formed from the bone marrow stem cells.