Abstract
Diabetes mellitus is one of the leading causes of morbidity and mortality in many countries and is considered as one of the epidemics of the twenty-first century. Current diabetes treatment is mostly based around daily insulin injection. Pancreas or islet transplantation first appeared as a good alternative, but lack of donor calls for more reliable clinical approaches. Recently, stem cell-based therapies have emerged as promising alternatives for pancreatic regenerative medicine. This chapter will review recent innovative clinical and preclinical applications used for diabetes treatment ranging from insulin injection to newly established cellular clinical trials with umbilical cord stem cells.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Limbert C, et al. Beta-cell replacement and regeneration: strategies of cell-based therapy for type 1 diabetes mellitus. Diabetes Res Clin Pract. 2008;79(3):389–99.
Sabin MA, Cameron FJ, Werther GA. Type 1 diabetes – still the commonest form of diabetes in children. Aust Fam Physician. 2009;38(9):695–7.
Sun B, et al. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure. Biochem Biophys Res Commun. 2007;354(4):919–23.
Montanya E. Islet- and stem-cell-based tissue engineering in diabetes. Curr Opin Biotechnol. 2004;15(5):435–40.
Wild S, et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047–53.
Mehers KL, Gillespie KM. The genetic basis for type 1 diabetes. Br Med Bull. 2008;88(1):115–29.
Aribi M. Candidate genes implicated in type 1 diabetes susceptibility. Curr Diabetes Rev. 2008;4(2):110–21.
MacFarlane AJ, Strom A, Scott FW. Epigenetics: deciphering how environmental factors may modify autoimmune type 1 diabetes. Mamm Genome. 2009;20(9–10):624–32.
Zipris D. Epidemiology of type 1 diabetes and what animal models teach us about the role of viruses in disease mechanisms. Clin Immunol. 2009;131(1):11–23.
Chowdhury TA, Mijovic CH, Barnett AH. The aetiology of type I diabetes. Baillieres Best Pract Res Clin Endocrinol Metab. 1999;13(2):181–95.
Kraine MR, Tisch RM. The role of environmental factors in insulin-dependent diabetes mellitus: an unresolved issue. Environ Health Perspect. 1999;107 Suppl 5:777–81.
Gremizzi C, et al. Impact of pancreas transplantation on type 1 diabetes-related complications. Curr Opin Organ Transplant. 2010;15(1):119–23.
de La Sierra A, Ruilope LM. Treatment of hypertension in diabetes mellitus. Curr Hypertens Rep. 2000;2(3):335–42.
Barrios V, Escobar C. Diabetes and hypertension. What is new? Minerva Cardioangiol. 2009;57(6):705–22.
Retnakaran R, Zinman B. Type 1 diabetes, hyperglycaemia, and the heart. Lancet. 2008;371(9626):1790–9.
Crawford TN, et al. Diabetic retinopathy and angiogenesis. Curr Diabetes Rev. 2009;5(1):8–13.
Sanchez AP, Sharma K. Transcription factors in the pathogenesis of diabetic nephropathy. Expert Rev Mol Med. 2009;11:e13.
Harris DT. Non-haematological uses of cord blood stem cells. Br J Haematol. 2009;147(2):177–84.
Liao YH, Verchere CB, Warnock GL. Adult stem or progenitor cells in treatment for type 1 diabetes: current progress. Can J Surg. 2007;50(2):137–42.
Clark PM. Assays for insulin, proinsulin(s) and C-peptide. Ann Clin Biochem. 1999;36(Pt 5):541–64.
Kelly WD, et al. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery. 1967;61(6):827–37.
Shapira Z, Yussim A, Mor E. Pancreas transplantation. J Pediatr Endocrinol Metab. 1999;12(1):3–15.
Lacy PE. Pancreatic transplantation as a means of insulin delivery. Diabetes Care. 1982;5 Suppl 1:93–7.
Ballinger WF, Lacy PE. Transplantation of intact pancreatic islets in rats. Surgery. 1972;72(2):175–86.
Shapiro AM, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230–8.
Azzi J, et al. Immunological aspects of pancreatic islet cell transplantation. Expert Rev Clin Immunol. 2010;6(1):111–24.
Close NC, Hering BJ, Eggerman TL. Results from the inaugural year of the Collaborative Islet Transplant Registry. Transplant Proc. 2005;37(2):1305–8.
Home PD, et al. A comparison of the activity and disposal of semi-synthetic human insulin and porcine insulin in normal man by the glucose clamp technique. Diabetologia. 1982;22(1):41–5.
Wilson ME, Scheel D, German MS. Gene expression cascades in pancreatic development. Mech Dev. 2003;120(1):65–80.
Bernardo AS, Hay CW, Docherty K. Pancreatic transcription factors and their role in the birth, life and survival of the pancreatic beta cell. Mol Cell Endocrinol. 2008;294(1–2):1–9.
Xu X, et al. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell. 2008;132(2):197–207.
Zaret KS. Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. Nat Rev Genet. 2008;9(5):329–40.
Sander M, German MS. The beta cell transcription factors and development of the pancreas. J Mol Med. 1997;75(5):327–40.
Zhou Q, et al. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008;455(7213):627–32.
Suzuki A, Nakauchi H, Taniguchi H. Glucagon-like peptide 1 (1–37) converts intestinal epithelial cells into insulin-producing cells. Proc Natl Acad Sci USA. 2003;100(9):5034–9.
Narushima M, et al. A human beta-cell line for transplantation therapy to control type 1 diabetes. Nat Biotechnol. 2005;23(10):1274–82.
Petropavlovskaia M, Rosenberg L. Identification and characterization of small cells in the adult pancreas: potential progenitor cells? Cell Tissue Res. 2002;310(1):51–8.
Bouwens L. Islet morphogenesis and stem cell markers. Cell Biochem Biophys. 2004;40(3 Suppl):81–8.
Bouwens L. Transdifferentiation versus stem cell hypothesis for the regeneration of islet beta-cells in the pancreas. Microsc Res Tech. 1998;43(4):332–6.
Wang RN, Kloppel G, Bouwens L. Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia. 1995;38(12):1405–11.
Rooman I, Lardon J, Bouwens L. Gastrin stimulates beta-cell neogenesis and increases islet mass from transdifferentiated but not from normal exocrine pancreas tissue. Diabetes. 2002;51(3):686–90.
Heremans Y, et al. Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3. J Cell Biol. 2002;159(2):303–12.
Taniguchi H, et al. beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther. 2003;10(1):15–23.
Zulewski H, et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes. 2001;50(3):521–33.
Hall PA, Lemoine NR. Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas. J Pathol. 1992;166(2):97–103.
Horb ME, et al. Experimental conversion of liver to pancreas. Curr Biol. 2003;13(2):105–15.
Ferber S, et al. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med. 2000;6(5):568–72.
Yang L, et al. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci USA. 2002;99(12):8078–83.
Yoshida S, et al. PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. Diabetes. 2002;51(8):2505–13.
Street CN, Rajotte RV, Korbutt GS. Stem cells: a promising source of pancreatic islets for transplantation in type 1 diabetes. Curr Top Dev Biol. 2003;58:111–36.
Mishra PK, et al. Stem cells as a therapeutic target for diabetes. Front Biosci. 2010;15:461–77.
Hori Y. Insulin-producing cells derived from stem/progenitor cells: therapeutic implications for diabetes mellitus. Med Mol Morphol. 2009;42(4):195–200.
Cai J, Weiss ML, Rao MS. In search of “stemness”. Exp Hematol. 2004;32(7):585–98.
McGuckin C, Forraz N. The umbilical cord: a rich and ethical stem cell source to advance regenerative medicine. Cell Prolif. 2011;44 Suppl 1:60–9.
McGuckin CP, Forraz N. Umbilical cord blood stem cells – an ethical source for regenerative medicine. Med Law. 2008;27(1):147–65.
McGuckin CP, Forraz N. Potential for access to embryonic-like cells from human umbilical cord blood. Cell Prolif. 2008;41 Suppl 1:31–40.
Kern S, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24(5):1294–301.
Leeb C, et al. Promising new sources for pluripotent stem cells. Stem Cell Rev. 2010;6(1):15–26.
Zhao Y, Wang H, Mazzone T. Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics. Exp Cell Res. 2006;312(13):2454–64.
Gao F, et al. Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells. Chin Med J (Engl). 2008;121(9):811–8.
Hu YH, et al. A secretory function of human insulin-producing cells in vivo. Hepatobiliary Pancreat Dis Int. 2009;8(3):255–60.
Beattie GM, et al. A novel approach to increase human islet cell mass while preserving beta-cell function. Diabetes. 2002;51(12):3435–9.
Itskovitz-Eldor J, et al. Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med. 2000;6(2):88–95.
Lumelsky N, et al. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science. 2001;292(5520):1389–94.
Jiang W, et al. In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Res. 2007;17(4):333–44.
Jiang Y, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418(6893):41–9.
Ianus A, et al. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest. 2003;111(6):843–50.
Oh 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(5):607–17.
Chen LB, Jiang XB, Yang L. Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World J Gastroenterol. 2004;10(20):3016–20.
Limbert C, Seufert J. In vitro (re)programming of human bone marrow stromal cells toward insulin-producing phenotypes. Pediatr Diabetes. 2009;10(6):413–9.
Karnieli O, et al. Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells. 2007;25(11):2837–44.
Koblas T, Harman SM, Saudek F. The application of umbilical cord blood cells in the treatment of diabetes mellitus. Rev Diabet Stud. 2005;2(4):228–34.
McGuckin CP, et al. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif. 2005;38(4):245–55.
McGuckin C, et al. Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro. Nat Protoc. 2008;3(6):1046–55.
Haller MJ, et al. Autologous umbilical cord blood infusion for type 1 diabetes. Exp Hematol. 2008;36(6):710–5.
Haller MJ, et al. Autologous umbilical cord blood transfusion in very young children with type 1 diabetes. Diabetes Care. 2009;32(11):2041–6.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag London
About this chapter
Cite this chapter
Le Roy, H., Forraz, N., Jurga, M., McGuckin, C.P. (2013). Umbilical Cord Stem Cells for Pancreatic Regenerative Medicine. In: Bhattacharya, N., Stubblefield, P. (eds) Human Fetal Tissue Transplantation. Springer, London. https://doi.org/10.1007/978-1-4471-4171-6_21
Download citation
DOI: https://doi.org/10.1007/978-1-4471-4171-6_21
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-4170-9
Online ISBN: 978-1-4471-4171-6
eBook Packages: MedicineMedicine (R0)