Diabetes, Vol 46, Issue 2 244-248, Copyright © 1997 by American Diabetes Association

ARTICLES

Functional beta-cell mass after transplantation of human fetal pancreatic cells: differentiation or proliferation?

GM Beattie, T Otonkoski, AD Lopez and A Hayek
Department of Pediatrics, The Whittier Institute, University of California San Diego, La Jolla 92037, USA.

The scarcity of human adult islets available for transplantation in IDDM makes the use of human fetal pancreatic cells desirable. Human fetal pancreatic cells grow and differentiate after transplantation in nude mice. It is unclear whether proliferation of preexisting endocrine cells or differentiation of precursor cells is mainly responsible for the increased islet mass and if beta-cell enrichment before transplantation enhances the functional outcome of the graft. To answer these questions, we transplanted purified human fetal islets, islet-like cell clusters (ICCs), and fresh tissue under the kidney capsule of nude mice. Insulin content was highest in the fresh tissue but fell rapidly during culture as either fetal islets or ICCs. Although fetal islets contained fourfold more insulin than ICCs before transplantation, the insulin content of the resulting grafts was the same after 3 months in vivo. The degree of stimulation after glucose challenge was comparable; however, more tissue was needed to generate the fetal islets. Grafts of fresh tissue also had similar total insulin contents, but when normalized to DNA, insulin concentration was significantly higher in the grafts from cultured tissue. Moreover, there were distinct morphological differences; the grafts from fresh tissue were more fibrous, with prominent ductal and cystic elements. Grafts from cultured tissue were two- to threefold enriched in endocrine tissue when compared with grafts originating from fresh tissue. These results suggest that islet cells identified in the grafted ICCs are mainly derived through differentiation of endocrine precursors and that cultured ICCs are more preferable than either fetal islets or uncultured tissue for transplantation.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L Banaei-Bouchareb, M Peuchmaur, P Czernichow, and M Polak A transient microenvironment loaded mainly with macrophages in the early developing human pancreas. J. Endocrinol., March 1, 2006; 188(3): 467 - 480. [Abstract] [Full Text] [PDF]

				W. L. Suarez-Pinzon, J. R. T. Lakey, S. J. Brand, and A. Rabinovitch Combination Therapy with Epidermal Growth Factor and Gastrin Induces Neogenesis of Human Islet {beta}-Cells from Pancreatic Duct Cells and an Increase in Functional {beta}-Cell Mass J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3401 - 3409. [Abstract] [Full Text] [PDF]

				S. Eventov-Friedman, H. Katchman, E. Shezen, A. Aronovich, D. Tchorsh, B. Dekel, E. Freud, and Y. Reisner Embryonic pig liver, pancreas, and lung as a source for transplantation: Optimal organogenesis without teratoma depends on distinct time windows PNAS, February 22, 2005; 102(8): 2928 - 2933. [Abstract] [Full Text] [PDF]

				J. C. Lopez-Talavera, A. Garcia-Ocana, I. Sipula, K. K. Takane, I. Cozar-Castellano, and A. F. Stewart Hepatocyte Growth Factor Gene Therapy for Pancreatic Islets in Diabetes: Reducing the Minimal Islet Transplant Mass Required in a Glucocorticoid-Free Rat Model of Allogeneic Portal Vein Islet Transplantation Endocrinology, February 1, 2004; 145(2): 467 - 474. [Abstract] [Full Text] [PDF]

				R. Gao, J. Ustinov, M.-A. Pulkkinen, K. Lundin, O. Korsgren, and T. Otonkoski Characterization of Endocrine Progenitor Cells and Critical Factors for Their Differentiation in Human Adult Pancreatic Cell Culture Diabetes, August 1, 2003; 52(8): 2007 - 2015. [Abstract] [Full Text] [PDF]

				B. R. Landau Methods for measuring glycogen cycling Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E413 - E419. [Abstract] [Full Text] [PDF]

				N. Trivedi, J. Hollister-Lock, M. D. Lopez-Avalos, J. J. O’Neil, M. Keegan, S. Bonner-Weir, and G. C. Weir Increase in {beta}-Cell Mass in Transplanted Porcine Neonatal Pancreatic Cell Clusters Is Due to Proliferation of {beta}-Cells and Differentiation of Duct Cells Endocrinology, May 1, 2001; 142(5): 2115 - 2122. [Abstract] [Full Text]

				C. Demeterco, G. M. Beattie, S. A. Dib, A. D. Lopez, and A. Hayek A Role for Activin A and Betacellulin in Human Fetal Pancreatic Cell Differentiation and Growth J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3892 - 3897. [Abstract] [Full Text]

				V. Cirulli, L. Crisa, G.M. Beattie, M.I. Mally, A.D. Lopez, A. Fannon, A. Ptasznik, L. Inverardi, C. Ricordi, T. Deerinck, et al. KSA Antigen Ep-CAM Mediates Cell-Cell Adhesion of Pancreatic Epithelial Cells: Morphoregulatory Roles in Pancreatic Islet Development J. Cell Biol., March 23, 1998; 140(6): 1519 - 1534. [Abstract] [Full Text] [PDF]

				A. Hayek and G. M. Beattie Experimental Transplantation of Human Fetal and Adult Pancreatic Islets J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2471 - 2475. [Abstract] [Full Text] [PDF]

				A. Ptasznik, G. M. Beattie, M. I. Mally, V. Cirulli, A. Lopez, and A. Hayek Phosphatidylinositol 3-Kinase Is a Negative Regulator of Cellular Differentiation J. Cell Biol., June 2, 1997; 137(5): 1127 - 1136. [Abstract] [Full Text] [PDF]