Pancreatic Endocrine and Exocrine Cell Ontogeny From Renal Capsule-transplanted Embryonic Stem Cells in Streptozocin-injured Mice

Maho Kodama ¹, Fumitaka Takeshita ¹, Shiro Kanegasaki ¹, Takahiro Ochiya ¹ and Gary Quinn ^1*

¹ Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo, Japan (MK,FT,TO,GQ), and Central Lab, Effector Cell Institute, Inc., Tokyo, Japan (SK,GQ)

^* To whom correspondence should be addressed. E-mail: garyquinn99{at}hotmail.com.

Submitted on May 15, 2007
Accepted on 31 August 2007

	Abstract

In this study we describe pancreatic cell ontogeny in renal capsule transplanted embryonic stem cells (ES) following injury by Streptozocin (STZ), demonstrating pancreatogenesis in situ. Seven week old female BALB/c nude mice were treated with either a single 175 or 200 mg/kg STZ dose, a regimen that induces substantial cell damage without overt hyperglycemia, and transplanted 24 hours later with 1x10⁵ ES. Immunohistochemistry was performed on ES tissue at 15, 21 and 28 days following transplantation using antibodies against stage- and lineage-specific pancreatic markers. After 21 days, PDX-1+ pancreatic foci first appeared in the renal capsule and expressed both amylase and endocrine hormones (insulin, glucagon and somatostatin). These foci increased in size by Day 28 due to acinar and duct cell proliferation, while endocrine cells remained non-dividing and comprised 2-4% of ES tumour volume. PDX-1, Nkx6.1, Ngn3 and ISL-1 protein localization patterns in pancreatic foci were comparable with embryonic pancreatogenesis. A prevalence of multihormonal endocrine cells, a characteristic of adult cell regeneration, indicated a possible divergence from embryonic islet cell development. The results indicate that cell damage, without overt hyperglycemia, induces a process of fetal-like pancreatogenesis in renal capsule transplanted ES, leading to cell neogenesis.

Key Words: regeneration, embryonic stem cells, pancreatic beta cells, pancreatogenesis, differentiation, diabetes, pancreas, hormone

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				M. Kodama, K. Tsukamoto, K. Yoshida, K. Aoki, S. Kanegasaki, and G. Quinn Embryonic Stem Cell Transplantation Correlates With Endogenous Neurogenin 3 Expression and Pancreas Regeneration in Streptozotocin-injured Mice J. Histochem. Cytochem., December 1, 2009; 57(12): 1149 - 1158. [Abstract] [Full Text] [PDF]

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