Plasticity after allogeneic hematopoietic stem cell transplantation

Abstract

The postulated almost unlimited potential of transplanted hematopoietic stem cells (HSCs) to transdifferentiate into cell types that do not belong to the hematopoietic system denotes a complete paradigm shift of the hierarchical hemopoietic tree. In several studies during the last few years, donor cells have been identified in almost all recipient tissues after allogeneic HSC transplantation (HSCT), supporting the theory that any failing organ could be accessible to regenerative cell therapy. However, the putative potential ability of the stem cells to cross beyond lineage barriers has been questioned by other studies which suggest that hematopoietic cells might fuse with non-hematopoietic cells and mimic the appearance of transdifferentiation. Proof that HSCs have preserved the capacity to transdifferentiate into other cell types remains to be demonstrated. In this review, we focus mainly on clinical studies addressing plasticity in humans who underwent allogeneic HSCT. We summarize the published data on non-hematopoietic chimerism, donor cell contribution to tissue repair, the controversies related to the methods used to detect donor-derived non-hematopoietic cells and the functional impact of this phenomenon in diverse specific target tissues and organs.

Persistence of recipient-type endothelium after allogeneic hematopoietic stem cell transplantation

“…1 In 1965, Medawar 2 hypothesized that longterm acceptance of solid organ transplants may be the result of replacement of their vascular endothelial cells by recipient-type cells leading to an endothelial cell chimerism. In particular, bone marrow-derived endothelial progenitor cells may replace damaged graft endothelium after rejection episodes.…”

PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

“…In skin, studies have shown that BM provides fibroblast-like cells in the dermis (of hematopoietic and mesenchymal lineages) and that the number of these cells increases after skin wounding (3,4). BM can also generate epithelial cells, i.e., keratinocytes, in the epithelia, although the precise derivations and mechanisms to raise BM-derived keratinocytes are not fully known (3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Human/mouse studies involving transplantation of sex-mismatched or genetically tagged BM cells have shown that keratin-positive bone marrow-derived cells can be found in skin epidermis, hair follicles, and sebaceous glands (6,8,9,11,12,14,16), sites that harbor skin stem cell niches (17).…”

Chimeric maternal cells in offspring do not respond to renal injury, inflammatory or repair signals

“…4 In healthy animals tissue injury induces cytokine expression to stimulate bone marrow-derived stem cells to emerge in the blood, migrate into injured tissues, and participate in tissue regeneration. [28][29][30][31] As autoimmune disease causes inflammation-mediated tissue injury, we hypothesized that elevated levels of MMc found in patients could be secondary to non-specific signals of inflammation or tissue injury, and thus a result, rather than a cause of chronic inflammation. We found in two distinct models of renal injury that maternal cells are not increased (either by expansion or recruitment) in response to tissue injury, inflammation, regeneration or fibrosis.…”