Purpose: To investigate the origin and localization of pancreatic stem cells in adult pancreatic tissues and to determine the primary mechanism underlying the participation of these cells in repairing pancreatic injuries. Methods: Sprague-Dawley rats were divided into experimental and control groups. The experimental group was given intraperitoneal injections of cerulein to induce acute pancreatitis. At 6 h, 1, 2, 3, 5 and 7 days, 5 rats from the experimental group and 2 rats from the control group were sacrificed; all sacrificed animals were intraperitoneally injected with 5-bromo-2′-deoxyuracil nucleotides (BrdU) 6 and 3 h prior to sacrifice. The pathological changes of pancreatic tissue were observed. The stem cell marker nestin and the cell proliferation marker BrdU were detected with immunohistochemistry. Pancreatic duodenal homeobox-1 (PDX-1) was determined by real-time PCR. Results: (1) The pathological changes of acute pancreatitis can be divided into three phases: the edema and apoptosis phase, the hemorrhagic necrosis phase, and the reconstruction phase. (2) Nestin-positive cells mainly appeared in the interlobular vascular lumen after cerulein injection, and they peaked at day 3 when the positive cells spread all over the pancreatic tissues. (3) BrdU-positive cells began to appear in the area surrounding the interlobular region, and the number of positive cells peaked on day 7. (4) The expression of PDX-1 mRNA initially increased, then decreased and gradually got close to a normal level. Conclusion: Primary pancreatic stem cells may not exist in the adult pancreatic tissues. The so-called pancreatic stem cells may actually originate from bone marrow stem cells. When pancreatic tissue is injured, bone marrow stem cells may participate in the repair.

1.
Brignier AC, Gewirtz AM: Embryonic and adult stem cell therapy. J Allergy Clin Immunol 2010;125(suppl 2):S336–S344.
2.
Hyun I: The bioethics of stem cell research and therapy. J Clin Invest 2010;120:71–75.
3.
Hviid Nielsen T: What happened to the stem cells? J Med Ethics 2008;34:852–857.
4.
Madsen OD: Pancreas phylogeny and ontogeny in relation to a ‘pancreatic stem cell’. C R Biol 2007;330:534–537.
5.
Yang C, Wang JM, Du CY, et al: Expression of stem cell markers CK-19 and PDX-1 mRNA in pancreatic islet samples of different purity from rats. Hepatobiliary Pancreat Dis Int 2007;6:544–548.
6.
Bhatia M, Wong FL, Cao Y, et al: Pathophysiology of acute pancreatitis. Pancreatology 2005;5:132–144.
7.
Gardner TB, Vege SS, Chari ST, et al: Faster rate of initial fluid resuscitation in severe acute pancreatitis diminishes in-hospital mortality. Pancreatology 2009;9:770–776.
8.
Dor Y, Brown J, Martinez OI, et al: Adult pancreatic β cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004;429:41–46.
9.
Levine F, Mercola M: No pancreatic endocrine stem cells? N Engl J Med 2005;351:1024–1026.
10.
Shi Y, Hou L, Tang F, et al: Inducing embryonic stem cells to differentiate into pancreatic β cells by a novel three-step approach with activin A and all-trans-retinoic acid. Stem Cells 2005;23:656–662.
11.
Oh SH, Muzzonigro TM, Bae SH, et al: Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab Invest 2004;84:607–617.
12.
Messam CA, Hou J, Berman JW, et al: Analysis of the temporal expression of nestin in human fetal brain derived neuronal and glial progenitor cells. Brain Res Dev Brain Res 2002;134:87–92.
13.
Lendahl U, Zimmerman LB, McKay RD: CNS stem cells express a new class of intermediate filament protein. Cell 1990;60:585–595.
14.
Dahlstrand J, Zimmerman LB, McKay RD, et al: Characterization of the human nestin gene reveals a close evolutionary relationship to neurofilaments. J Cell Sci 1992;103:589–597.
15.
Wislet-Gendebien S, Hans G, Leprince P, et al: Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells 2005;23:392–402.
16.
Abraham EJ, Leech CA, Lin JC, et al: Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells. Endocrinology 2002;143:3152–3161.
17.
Huang H, Tang X: Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas. Lab Invest 2003;83:539–547.
18.
Hunziker E, Stein M: Nestin-expressing cells in the pancreatic islets of Langerhans. Biochem Biophys Res Commun 2000;271:116–119.
19.
Humphrey RK, Bucay N, Beattie GM, et al: Characterization and isolation of promoter-defined nestin-positive cells from the human fetal pancreas. Diabetes 2003;52:2519–2525.
20.
Street CN, Lakey JR, Seeberger K, et al: Heterogenous expression of nestin in human pancreatic tissue precludes its use as an islet precursor marker. J Endocrinol 2004;180:213–225.
21.
Ishiwata T, Kudo M, Onda M, et al: Defined localization of nestin-expressing cells in L-arginine-induced acute pancreatitis. Pancreas 2006;32:360–368.
22.
Dutta S, Gannon M, Peers B, et al: PDX: PBX complexes are required for normal proliferation of pancreatic cells during development. Proc Natl Acad Sci USA 2001;98:1065–1070.
23.
Jonsson J, Carlsson L, Edlund T, et al: Insulin promoter-factor 1 is required for pancreas development in mice. Nature 1994;371:606–609.
24.
Taguchi M, Otsuki M: Co-localization of nestin and PDX-1 in small evaginations of the main pancreatic duct in adult rats. J Mol Histol 2004;35:785–789.
25.
Gagliardino JJ, Del Zotto H, Massa L, et al: Pancreatic duodenal homeobox-1 and islet neogenesis-associated protein: a possible combined marker of activateable pancreatic cell precursors. J Endocrinol 2003;177:249–259.
26.
Liu T, Wang CY, Gou SM, et al: PDX-1 expression and proliferation of duct epithelial cells after partial pancreatectomy in rats. Hepatobiliary Pancreat Dis Int 2007;6:424–429.
27.
Bhatia M: Apoptosis versus necrosis in acute pancreatitis. Am J Physiol 2004;286:G189–G196.
28.
Campo GM, Avenoso A, Campo S, et al: Chondroitin-4-sulphate reduced oxidative injury in caerulein-induced pancreatitis in mice: the involvement of NF-ĸB translocation and apoptosis activation. Exp Biol Med 2008;233:741–752.
29.
Zulewski H, Abraham EJ, Gerlach MJ, et al: Multipotential nest in positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001;50:521–533.
30.
Trulsson L, Sandström P, Sundqvist T, et al: The Influence of a load of L-arginine on serum amino acids and pancreatic apoptosis/proliferation and ATP levels in the rat. Pancreas 2004;29:113–120.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.