Simultaneous bone marrow and intestine transplantation promotes marrow-derived hematopoietic stem cell engraftment and chimerism

Abstract

Organ allografts have been shown to provide a syngeneic microenvironment for organ-based donor hematopoietic stem cells to maintain long-lasting chimerism after transplantation. We hypothesized that organ allografts would also support engraftment and hematopoiesis of adjunctively infused donor marrow stem cells, syngeneic to organ grafts, in nonmyeloablated recipients. In BN-to-LEW and GFPto-ACI rat combinations, donor bone marrow (BM) infusion together with small intestine transplantation (SITx) under short-course tacrolimus immunosuppression resulted in persistent macrochimerism (more than 5%) for 150 days. In contrast, after BM infusion or SITx alone, chimerism was temporary and disappeared by day 100. Y-chromosome polymerase chain reaction (PCR) in sexmismatched male BM plus female intestine or female BM plus male intestine transplantation into female recipients suggested that persistent macrochimerism was derived from infused BM. BM infusion together with lymphoid-depleted intestine grafts also supported macrochimerism development; however, thirdparty intestine grafts did not.

Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD

“…Should larger studies reproduce our findings, routine monitoring of mixed chimerism may become a very useful tool for treatment tailoring after intestinal and multivisceral transplantation. These studies might also pave the way for pilot protocols combining bone marrow and intestinal transplantation, such as those established in rodents, to promote donor-specific tolerance (50). …”

CTGF, intestinal stellate cells and carcinoid fibrogenesis

“…These functional data, together with the immunohistochemical evidence of activated intestinal stellate cells in situ, strongly suggest that carcinoid-induced fibrosis is a stellate-cell induced phenomenon. It is possible that the "intestinal stellate" cell could be derived from precursor cells in blood stream and there is some evidence that bone marrow-derived cells can migrate into the SI [29] . A study of hepatic stellate cells, however, conclusively identified that these cells were not derived from bone marrow derived fibrocytes [30] .…”

Characterization of Transplanted Green Fluorescent Protein+ Bone Marrow Cells into Adipose Tissue

“…In 2002, Körbling et al reported that recipients of peripheral blood stem cells showed donor-derived hepatocytes up to 7% in liver tissue specimens endothelium by bone-marrow-derived cells [33]. Recently, Nakao et al reported that infused bone marrow stem cells engraft into both the allogeneic marrow environment and the syngeneic extramarrow environment (intestinal graft) [34].…”