Role of stem cell trafficking and donor???recipient cellular chimerism in lung transplantation

Abstract

Purpose of review Since the introduction of modern immunosuppressive drugs, acute episodes of cellular allograft rejection can be resolved in most cases. The long-term success of organ transplantation is challenged by chronic allograft damage induced by immunologic and nonimmunologic injury. Because of the multifactorial pathogenesis, currently no causal therapy for chronically damaged transplants is available. The regeneration of irreversible damaged allografts by pluripotent stem cells represents an intriguing possibility to improve long-term function of solid organ transplants. Recent findings Numerous studies were able to demonstrate a simultaneous presence of donor- and recipient-derived organ-specific cells within an allograft, a phenomenon called in situ microchimerism. Pluripotent progenitor cells from the bone marrow of the recipient are most likely the source of intraorgan chimerism. Adult stem cells appear to be able to cross the boundaries of the original embryonic cell layers and may have the capacity to help restore damaged tissue in a variety of organs. However, it could be shown that a higher degree of intraorgan chimerism is not correlated with an improved graft prognosis, but indicates more severe organ damage. Summary Recipient-derived progenitor cells invade an allograft and differentiate into organ specific cells. This in situ microchimerism increases with the degree of tissue injury but is under current conditions not sufficient to prevent limited long-term function of most allografts. Because the detailed mechanisms of progenitor cell differentiation or stem cell transdifferentiation are not elucidated, much more must be known about the biology of these enigmatic cells to exploit their therapeutic capacity to injured organs.