Minimal evidence of transdifferentiation from recipient bone marrow to parenchymal cells in regenerating and long-surviving human allografts

Tong Wu, Kathleen Cieply, Michael A. Nalesnik, Parmjeet S. Randhawa, Aurelio Sonzogni, C. Bellamy, Kareem Abu-Elmagd, George K. Michalopolous, Ronald Jaffe, Robert L. Kormos, Bruno Gridelli, John J. Fung, Anthony J. Demetris

Research output: Contribution to journalArticlepeer-review

Abstract

Liver, small intestine, and heart allografts in residence for 4 days to 16 years were analyzed by simultaneous XY fluorescent in situ hybridization to search for evidence of the recently described process of transdifferentiation of recipient bone marrow stem cells to allograft parenchymal cells. These studies were carried out in an effort to find conditions associated with maximal levels of engraftment or expansion of the recipient parenchymal cells. Despite prolonged survival up to 16 years, regeneration after severe preservation injury or use of split livers, only rare, isolated and tentatively identified recipient hepatocytes were detected in liver allografts. In intestinal allografts, despite survival of up to 8 years and extensive mucosal regeneration because of severe damage from acute rejection, there was no crypt replacement by recipient epithelial cells. In cardiac allografts, no recipient myocytes were detected despite recipient survival for 2-3 days and 3-4 weeks after myocardial infarcts at 5 and 8 years after transplantation. Parenchymal cell transdifferentiation from recipient bone marrow stem cells was rare to nonexistent in severely injured, regenerating, and long-surviving allografts. The rare isolated recipient parenchymal cells tentatively identified did not appear to behave as stem cells: they did not form clusters and did not increase with time after transplantation. Because of the extremely low frequency, interpretation was difficult. Regardless of these results, a more vigorous search for conditions that promote transdifferentiation is warranted.

Original languageEnglish
Pages (from-to)1173-1181
Number of pages9
JournalAmerican Journal of Transplantation
Volume3
Issue number9
DOIs
Publication statusPublished - Sep 2003

Keywords

  • Allografts
  • Bone marrow
  • Stem cells
  • Transdifferentiation

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Minimal evidence of transdifferentiation from recipient bone marrow to parenchymal cells in regenerating and long-surviving human allografts'. Together they form a unique fingerprint.

Cite this