New insights in the development of biological chimeras: Genomic instability and epithelial chimerism after hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in humans results in true biological chimeras. While circulating hematopoietic and immune cells and their tissue derivatives (e.g., Kupffer cells, Langerhans cells) become donor genotype after transplantation, other cells remain recipient in origin. This unphysiological formation of biological chimeras is not free of consequences. The first sequel which has been recognized in the development of chimerical organisms after allo-HSCT is the graft versus host reaction, in which the new developed immune cells from the graft recognize the host's epithelial cells as foreign and kill them. There is now accumulating evidence that there are also other consequences in the co-existence of two genetically distinct populations in the transplant recipient. First, epithelial cells with donor-derived genotype emerge. Second, epithelial tissues of the host acquire genomic alterations. The current chapter discusses existing data on these recently discovered phenomena and focuses on their pathogenesis, clinical significance and therapeutic implications.