help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Beattie, G. M.
Right arrow Articles by Hayek, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Beattie, G. M.
Right arrow Articles by Hayek, A.
The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 6 1852-1856
Copyright © 1997 by The Endocrine Society

Experimental Studies

Ex Vivo Expansion of Human Pancreatic Endocrine Cells1

Gillian M. Beattie, Vincenzo Cirulli2, Ana D. Lopez and Alberto Hayek

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

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

Cell transplantation as a therapy for type 1 diabetes is facilitated by ex vivo cell expansion of pancreatic ß-cells without loss of differentiative characteristics. The aim of this study was to determine the optimal conditions for in vitro growth of functional human pancreatic endocrine tissue. We examined the mitogenicity of matrixes from a variety of cell lines; proliferation was greater in cells growing on matrixes from bladder carcinoma cell lines, especially in monolayers grown on matrix from the human cell line HTB-9. After 14-day culture, there was a more than 100-fold proliferative increase, which was augmented to a more than 200-fold when hepatocyte growth factor/scatter factor was added; however, hepatocyte growth factor/scatter factor induced a rapid decrease in insulin content. Without the growth factor, fetal cell monolayers expanded 4-fold with no insulin loss; however, after 12-fold expansion, the insulin levels decreased to 40% of those in unexpanded cells. Adult islet cells expanded 3-fold without insulin loss. After 5-fold expansion, insulin levels decreased by 25% compared to those in free floating islets while retaining a normal response to secretagogues. Together, these results indicate that HTB-9 matrix provides the best stimulatory effect on replication of human endocrine cells, with little loss of in vitro function.




This article has been cited by other articles:


Home page
 Physiol. GenomicsHome page
B. Kutlu, A. G. Kayali, S. Jung, G. Parnaud, D. Baxter, G. Glusman, N. Goodman, L. A. Behie, A. Hayek, and L. Hood
Meta-analysis of gene expression in human pancreatic islets after in vitro expansion
Physiol Genomics, September 1, 2009; 39(1): 72 - 81.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
M. V Joglekar, V. M Joglekar, S. V Joglekar, and A. A Hardikar
Human fetal pancreatic insulin-producing cells proliferate in vitro
J. Endocrinol., April 1, 2009; 201(1): 27 - 36.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
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]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. J. Meier, R. Kayed, C.-Y. Lin, T. Gurlo, L. Haataja, S. Jayasinghe, R. Langen, C. G. Glabe, and P. C. Butler
Inhibition of human IAPP fibril formation does not prevent beta-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP
Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1317 - E1324.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
T. Kaido, M. Yebra, V. Cirulli, C. Rhodes, G. Diaferia, and A. M. Montgomery
Impact of Defined Matrix Interactions on Insulin Production by Cultured Human {beta}-Cells: Effect on Insulin Content, Secretion, and Gene Transcription.
Diabetes, October 1, 2006; 55(10): 2723 - 2729.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
A. S. Narang and R. I. Mahato
Biological and biomaterial approaches for improved islet transplantation.
Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C.-Y. Lin, T. Gurlo, L. Haataja, W. A. Hsueh, and P. C. Butler
Activation of Peroxisome Proliferator-Activated Receptor-{gamma} by Rosiglitazone Protects Human Islet Cells against Human Islet Amyloid Polypeptide Toxicity by a Phosphatidylinositol 3'-Kinase-Dependent Pathway
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6678 - 6686.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Kaido, M. Yebra, V. Cirulli, and A. M. Montgomery
Regulation of Human {beta}-Cell Adhesion, Motility, and Insulin Secretion by Collagen IV and Its Receptor {alpha}1{beta}1
J. Biol. Chem., December 17, 2004; 279(51): 53762 - 53769.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Kaido, B. Perez, M. Yebra, J. Hill, V. Cirulli, A. Hayek, and A. M. Montgomery
{alpha}v-Integrin Utilization in Human {beta}-Cell Adhesion, Spreading, and Motility
J. Biol. Chem., April 23, 2004; 279(17): 17731 - 17737.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
R. A. Ritzel and P. C. Butler
Replication Increases {beta}-Cell Vulnerability to Human Islet Amyloid Polypeptide-Induced Apoptosis
Diabetes, July 1, 2003; 52(7): 1701 - 1708.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. Demeterco, P. Itkin-Ansari, B. Tyrberg, L. P. Ford, R. A. Jarvis, and F. Levine
c-Myc Controls Proliferation Versus Differentiation in Human Pancreatic Endocrine Cells
J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3475 - 3485.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
V. Cirulli, G. M. Beattie, G. Klier, M. Ellisman, C. Ricordi, V. Quaranta, F. Frasier, J. K. Ishii, A. Hayek, and D. R. Salomon
Expression and Function of {alpha}v{beta}3 and {alpha}v{beta}5 Integrins in the Developing Pancreas: Roles in the Adhesion and Migration of Putative Endocrine Progenitor Cells
J. Cell Biol., September 18, 2000; 150(6): 1445 - 1460.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Bonner-Weir, M. Taneja, G. C. Weir, K. Tatarkiewicz, K.-H. Song, A. Sharma, and J. J. O'Neil
In vitro cultivation of human islets from expanded ductal tissue
PNAS, July 5, 2000; 97(14): 7999 - 8004.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society