Title:
Regeneration of the pancreas: does it happen in adult?

Shigeru B.H. Ko, MD, PhD
Department of Systems Medicine, Sakaguchi Laboratory,
Keio University school of Medicine , Tokyo , Japan

Abstract:
Recent progress in regenerative medicine has made it possible to generate mature differentiated cells from embryonic stem (ES) cells or induced pluripotent stem (iPS) cells. Moreover, it has become possible to generate mature differentiated hepatocytes or cardiomyocytes directly from skin fibroblasts by a method called direct reprogramming with some defined transcription factors. Recent success of in-vitro cultivaion of intestinal tissue stem cells as an organoid support the notion that eventually, all types of tissue stem cells in our body will become cultivable and will be used in the future, cell replacement, regenerative medicine.

Pancreas is both a digestive and endocrine organ which plays pivotal roles in the digestion of foods and stabilization of blood glucose levels. Persistent or repeated inflammation, called chronic pancreatitis, destroys both exocrine and endocrine functions of the organ, and leads to disappearance of both exocrine and endocrine cells from the organ. Chronic pancreatitis are frequently associated with severe forms of malnutrition and diabetes mellitus. As these diseases require life-long treatment, it is desirable to develop more effective treatment for these diseases.

In this lecture, I will discuss a possibility of regeneration of adult pancreas based on our own findings: we first noticed the regeneration of adult pancreas, while we treated patients with chronic pancreatitis with severe malnutrition and diabetes mellitus. We found that an anti-inflammatory treatment with corticosteroids restored exocrine and endocrine functions in patients with autoimmune pancreatitis, one form of idiopathic chronic pancreatitis. Moreover, these functional recoveries are accompanied with massive regeneration of pancreatic parenchymal cells. I will discuss implication of these findings and provide perspectives in the field of pancreatic tissue regeneration and restoration.

References:
1. Ko SB, Azuma S, Yokoyama Y, Yamamoto A, Kyokane K, Niida S, Ishiguro H, Ko MS. Inflammation increases cells expressing ZSCAN4 and progenitor-cell markers in the adult pancreas. Am J Physiol. 2013 ;304(12):G1103-16.

2. Ko SB, Mizuno N, Yatabe Y, Yoshikawa T, Ishiguro H, Yamamoto A, Azuma S, Naruse S, Yamao K, Muallem S, Goto H. Corticosteroids correct aberrant CFTR localization in the duct and regenerate acinar cells in autoimmune pancreatitis. Gastroenterology. 2010 138(5):1988-96.