Control of “reprogramming in vivo” might suppress organ failure progression?

Abstract

Recent progress of regenerative medicine is largely attributable to the discovery of genomic reprogramming. Reprogramming provides transdifferentiation capability and even pluripotency to mature cells. We have found a stem cell formation from mature pancreatic acinar cells by specific growth factor treatment in mouse. The changes in gene expression were somewhat suggestive of dedifferentiation or early phase of carcinogenesis. Epithelial-mesenchymal transition is also related to both embryogenesis and carcinogenesis. Pathology of chronic pancreatitis is typified by degenerative change of acinar area and granuloma formation. Pathologically granuloma is determined as newly-grown compensatory tissue, but here we propose another etiology, a consequence of epithelial-mesenchymal transition; i.e., the granulomatous tissue may be originated from reprogrammed somatic stem cells. Cylopamine, an inhibitor of Sonic hedgehogh(SHH) pathway, is an effective carcinostatic drug and its mechanism is thought to be a suppression of epithelial-mesenchymal transition. Metformin, a diabetic drug and SHH inhibitor, has also shown a hopeful anti-cancer effect. Clinical and research experiences lead us to a presumption that organ failure is an outcome of epithelial-mesenchymal transition caused by “reprogramming in vivo”. In other words, to control “reprogramming in vivo” may prevent the progress of organ failure. Japan Society for Organ Preservation and Biology consists of researchers in not only transplantation surgery but also basic medicine, precision engineering, pharmacy, and life sciences. Authors wish this review may open up a novel research filed of the Society member.