This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hayek, A. Articles by Beattie, G. M. Search for Related Content PubMed PubMed Citation Articles by Hayek, A. Articles by Beattie, G. M.

Experimental Transplantation of Human Fetal and Adult Pancreatic Islets¹

Department of Pediatrics, The Whittier Institute, University of California-San Diego School of Medicine, La Jolla, California 92037

Address all correspondence and requests for reprints to: A. Hayek, M.D., Department of Pediatrics, The Whittier Institute, 9894 Genesee Avenue, La Jolla, California 92037. E-mail ahayek{at}ucsd.edu

We examined morphology and function following transplantation of human fetal islet-like clusters (ICCs) in nude mice and compared the functional efficiency of human adult islets and fetal ICCs after transplantation. To assess the optimal site we first transplanted ICCs under the kidney capsule, pancreas, lung, and liver in nude mice. Grafts to the kidney and pancreas matured functionally and morphologically, as evidenced by a 4-fold increase in C peptide after glucose stimulation and the presence of insulin in the grafts of all animals. Grafts to the lung, liver, and spleen did poorly; C peptide was only measurable in two of eight, two of five, or three of five of mice grafted to the lung, liver, or spleen, respectively. Using chemically diabetic nude rats as recipients, we were able to restore normoglycemia using 15,000 ICCs/kg. Lastly, when transplanted under the kidney capsule of normal nude mice, ICCs had significantly higher insulin contents and C peptide release than equivalent grafts of adult islets. In summary, ICCs are an efficient source of insulin-producing cells of potential use in clinical transplantation. In nude mice, both the kidney and the pancreas provide suitable environments for the growth and maturation of undifferentiated human ß-cells.

This article has been cited by other articles:

				N. Fiaschi-Taesch, T. A. Bigatel, B. Sicari, K. K. Takane, F. Salim, S. Velazquez-Garcia, G. Harb, K. Selk, I. Cozar-Castellano, and A. F. Stewart Survey of the Human Pancreatic {beta}-Cell G1/S Proteome Reveals a Potential Therapeutic Role for Cdk-6 and Cyclin D1 in Enhancing Human {beta}-Cell Replication and Function In Vivo Diabetes, April 1, 2009; 58(4): 882 - 893. [Abstract] [Full Text] [PDF]

				K. Brands, E. Colvin, L. J. Williams, R. Wang, R. B. Lock, and B. E. Tuch Reduced Immunogenicity of First-Trimester Human Fetal Pancreas Diabetes, March 1, 2008; 57(3): 627 - 634. [Abstract] [Full Text] [PDF]

				A. G. Kayali, L. E. Flores, A. D. Lopez, B. Kutlu, E. Baetge, R. Kitamura, E. Hao, G. M. Beattie, and A. Hayek Limited Capacity of Human Adult Islets Expanded In Vitro to Redifferentiate Into Insulin-Producing {beta}-Cells Diabetes, March 1, 2007; 56(3): 703 - 708. [Abstract] [Full Text] [PDF]

				R. K. Humphrey, N. Bucay, G. M. Beattie, A. Lopez, C. A. Messam, V. Cirulli, and A. Hayek Characterization and Isolation of Promoter-Defined Nestin-Positive Cells from the Human Fetal Pancreas Diabetes, October 1, 2003; 52(10): 2519 - 2525. [Abstract] [Full Text] [PDF]

				G. M. Beattie, A. M.P. Montgomery, A. D. Lopez, E. Hao, B. Perez, M. L. Just, J. R.T. Lakey, M. E. Hart, and A. Hayek A Novel Approach to Increase Human Islet Cell Mass While Preserving {beta}-Cell Function Diabetes, December 1, 2002; 51(12): 3435 - 3439. [Abstract] [Full Text] [PDF]

				J. Movassat, G. M. Beattie, A. D. Lopez, and A. Hayek Exendin 4 Up-Regulates Expression of PDX 1 and Hastens Differentiation and Maturation of Human Fetal Pancreatic Cells J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4775 - 4781. [Abstract] [Full Text] [PDF]

				D. Dufayet de la Tour, T. Halvorsen, C. Demeterco, B. Tyrberg, P. Itkin-Ansari, M. Loy, S.-J. Yoo, E. Hao, S. Bossie, and F. Levine {beta}-Cell Differentiation from a Human Pancreatic Cell Line in Vitro and in Vivo Mol. Endocrinol., March 1, 2001; 15(3): 476 - 483. [Abstract] [Full Text]