Hematopoietic chimerisms: friends or foes?

Abstract

In humans, chimerisms (Chs) can occur naturally or be induced through artificial means. Feto-maternal Chs are natural and result from the spontaneous trafficking of hematopoietic or other types of cells across the placenta during pregnancy. These Chs can be transient or persist for many years and even decades. Mixed hematopoietic Chs (MHChs) can also be artificially induced, and they might have profound effects on the modulation of the immune system, which can be used for inducing donor-specific tolerance in recipients of allogeneic organ transplantation. Nonetheless, the main obstacle for the establishment of such Chs is that they require the engraftment of donor hematopoietic cells, which at present can only be accomplished using relatively toxic regimens that preclude its widespread use and currently restricts its application to some special patients, in which both a solid organ (e.g. a renal allograft) and a marrow transplantation are necessary. However, it is likely that less toxic strategies are developed that can be clinically applicable in the next decade to induce tolerance in organ transplantation. A variant of Chs is the molecular Chs, in which a proportion of the hematopoietic cells would be transduced to express a transgene (e.g. encoding a therapeutic protein, an auto-antigen, or an allergen), so that specific tolerance to these molecules is induced. This might have therapeutic applications in fields such as replacement and genetic therapies, autoimmune diseases, or allergy.