Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Abstract 


Background

Recent reports have shown evidence of host derived parenchymal engraftment in several human allografts including the lung, leading to speculation that stem cell therapy may be useful for lung repair in diseases such as cystic fibrosis (CF). To date, previous studies have looked at single surgical or autopsy specimens and no longitudinal studies have been reported. The aim of this study was to assess whether transbronchial biopsies could be used to study the time course of chimerism following lung transplantation.

Methods

Specimens of archived transbronchial lung biopsies from five time points taken for clinical purposes from two boys who had received a sex mismatched heart-lung transplant for end stage CF were examined. Sections were dual stained for cytokeratin (epithelium) and a mixture of leucocyte common antigen and CD68 for inflammatory cells. Co-localisation of cells containing a Y chromosome was confirmed by fluorescent in situ hybridisation.

Results

Evidence of chimerism was found in up to 6.6% of epithelial cells in bronchial (median 1.4% (range 0-6.6)) and alveolar (median 3.6% (range 2.3-5.5) tissue without apparent evidence of fusion. This engraftment was seen as early as 3 weeks and remained relatively constant up to 37 months.

Conclusions

This study has demonstrated proof of principle for long term chimerism in lung epithelium. Transbronchial biopsies may provide a new method for studying the kinetics of stem cell engraftment in the lung.

Free full text 


Logo of thoraxLink to Publisher's site
Thorax. 2005 Jan; 60(1): 60–62.
PMCID: PMC1747166
PMID: 15618585

Transbronchial biopsies provide longitudinal evidence for epithelial chimerism in children following sex mismatched lung transplantation

Abstract

Background: Recent reports have shown evidence of host derived parenchymal engraftment in several human allografts including the lung, leading to speculation that stem cell therapy may be useful for lung repair in diseases such as cystic fibrosis (CF). To date, previous studies have looked at single surgical or autopsy specimens and no longitudinal studies have been reported. The aim of this study was to assess whether transbronchial biopsies could be used to study the time course of chimerism following lung transplantation.

Methods: Specimens of archived transbronchial lung biopsies from five time points taken for clinical purposes from two boys who had received a sex mismatched heart-lung transplant for end stage CF were examined. Sections were dual stained for cytokeratin (epithelium) and a mixture of leucocyte common antigen and CD68 for inflammatory cells. Co-localisation of cells containing a Y chromosome was confirmed by fluorescent in situ hybridisation.

Results: Evidence of chimerism was found in up to 6.6% of epithelial cells in bronchial (median 1.4% (range 0–6.6)) and alveolar (median 3.6% (range 2.3–5.5) tissue without apparent evidence of fusion. This engraftment was seen as early as 3 weeks and remained relatively constant up to 37 months.

Conclusions: This study has demonstrated proof of principle for long term chimerism in lung epithelium. Transbronchial biopsies may provide a new method for studying the kinetics of stem cell engraftment in the lung.

Full Text

The Full Text of this article is available as a PDF (153K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Grove Joanna E, Lutzko Carolyn, Priller Josef, Henegariu Octavian, Theise Neil D, Kohn Donald B, Krause Diane S. Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium. Am J Respir Cell Mol Biol. 2002 Dec;27(6):645–651. [Abstract] [Google Scholar]
  • Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 2001 May 4;105(3):369–377. [Abstract] [Google Scholar]
  • Kotton DN, Ma BY, Cardoso WV, Sanderson EA, Summer RS, Williams MC, Fine A. Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development. 2001 Dec;128(24):5181–5188. [Abstract] [Google Scholar]
  • Suratt Benjamin T, Cool Carlyne D, Serls Amanda E, Chen Lin, Varella-Garcia Marileila, Shpall Elizabeth J, Brown Kevin K, Worthen G Scott. Human pulmonary chimerism after hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2003 Aug 1;168(3):318–322. [Abstract] [Google Scholar]
  • Mattsson Jonas, Jansson Monika, Wernerson Annika, Hassan Moustapha. Lung epithelial cells and type II pneumocytes of donor origin after allogeneic hematopoietic stem cell transplantation. Transplantation. 2004 Jul 15;78(1):154–157. [Abstract] [Google Scholar]
  • Kleeberger Wolfram, Versmold Anne, Rothämel Thomas, Glöckner Sabine, Bredt Martin, Haverich Axel, Lehmann Ulrich, Kreipe Hans. Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury. Am J Pathol. 2003 May;162(5):1487–1494. [Europe PMC free article] [Abstract] [Google Scholar]
  • Johnson LG, Olsen JC, Sarkadi B, Moore KL, Swanstrom R, Boucher RC. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat Genet. 1992 Sep;2(1):21–25. [Abstract] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

Citations & impact 


Impact metrics

Jump to Citations

Citations of article over time

Article citations


Go to all (42) article citations