This is particularly evident when the recipient organ is damaged. Bone marrow derived cells can either engraft or fuse to adopt, or be reprogrammed, to the differentiated state of the particular epithelia. This suggests that the endogenous stem cell of an organ, and its role in growth and regeneration, is not confined to each specific organ but may be a dynamic system involving circulating BMDC with stem cell niche environments regulating recruitment, proliferation and differentiation. This may have significant implications concerning the evolution of cancers in many solid organs, including the pancreas. Houghton et al demonstrated that in a model of Helicobacter felis induced gastric carcinogenesis, the development of metaplasia and dysplasia was linked to the engraftment and expansion of the BMDC population, eventually giving rise to gastric adenocarcinoma. Observations in women who received bone marrow transplants from male donors, and who subsequently developed a cancer, identified that myofibroblasts within these tumors were derived from donor bone marrow. The majority of previous studies assessing the role of BMDC in pancreatic regeneration and repair have concentrated on restoring endocrine function following islet cell injury. Few studies have focussed on the contribution of BMDC to growth and regeneration of the exocrine pancreas, or their role in pancreatic cancer. Wang et al describe the contribution of BMDC to pancreatic duct formation in neonatal mice, Marrache et al, and Watanabe et al demonstrate in a model of caerulein induced chronic pancreatitis that BMDC contribute to the pancreatic stellate cell population suggesting a role in tissue repair, while more recently Pan et al identified a contribution of BMDC to the pancreatic stellate cell population in a rat model of chemical carcinogenesis. Here we generate a robust model of whole bone marrow transplantation to show that in pancreatic carcinogenesis, and in chronic pancreatitis, BMDC contribute significantly to the activated pancreatic stellate cell population. From 1 month after DMBA treatment, pancreatic precursor lesions with varying degrees of dysplasia were Z-VAD-FMK present. Foci of adenocarcinoma in relation to mPanIN were seen in the pancreas from 2 months after DMBA, while ductal adenocarcinoma developed at 3–4 months. This phenotype closely resembled that seen in a similar model used by Kimura et al. We assessed the contribution of BMDC to the desmoplastic stroma, in particular to the population of pancreatic stellate cells, by assessing co-expression of GFP and the stellate cell selective markers desmin, glial fibrillary acidic protein, a-smooth muscle actin, the co-expression of which defines activated stellate cells. These markers, originally identified as PaSC specific, are used to distinguish PaSC’s from normal fibroblasts due to the co-expression of the intermediate filament proteins desmin and GFAP, while expression of aSMA in PaSC’s was originally described as a source of fibrosis in chronic pancreatitis and pancreatic cancer, designating activated PaSC’s. There was significant BMDC recruitment to the stroma surrounding precursor lesions following DMBA treatment.