Skip to main content
SpringerLink
Log in
Book cover

Islets of Langerhans, 2. ed. pp 1–23Cite as

Stem Cells in Pancreatic Islets

  • Living reference work entry
  • First Online:

  • 120 Accesses

Abstract

Adult stem cells are unspecialized cells with the capacity to differentiate into many different cell types in the body. These cells together with the progenitor cells involve in the tissue repair processes and maintain the functionality of the tissue in which they are found. During the onset and progression of the diabetes mellitus type 1, the beta cells in Langerhans islets undergo progressive and selective destruction. To restore the normal insulin levels to regulate glucose homeostasis, the dropping number of beta cells is replaced by progenitor/stem cells in the environment of pancreatic islets. Due to the complexity of the organ organization, these cells could originate from different sources. In this chapter, the types of the stem cells derived from pancreatic environment with the differentiation capacity into pancreatic islets and their cells were mainly focused. Some of these cells do not only involve in the regeneration of insulin-producing cells, but they also function in the preservation of beta cell viability. Besides providing an alternative renewable source for beta cell replacement, the interaction of pancreatic stem cells with immune system in diabetes mellitus type 1 is also discussed.

This is a preview of subscription content, log in via an institution.

Abbreviations

ACTA2:

Actin alpha 2 (smooth muscle actin)

CHIBs:

Cultured human islet buds

ECFP:

Cyan fluorescent protein

FACS:

Fluorescence-activated cell sorting

FGF:

Fibroblast growth factors

GLP-1:

Glucagon-like peptide-1

HGF:

Hepatocyte growth factor

ICAM-1:

Intercellular adhesion molecule 1 (CD54)

IFN-g:

Interferon gamma

IL-:

Interleukin

MSCs:

Mesenchymal stem cells

NG2:

Neuron-glial antigen 2

NOD:

Nonobese diabetic

PDGFRb:

Platelet-derived growth factor receptor, beta polypeptide

PDX-1:

Pancreatic duodenal homeobox-containing factor-1

PI-SCs:

Pancreatic islet-derived stem cells

TGF-a:

Transforming growth factor alpha

TGF-b:

Transforming growth factor beta

TNF-a:

Tumor necrosis factor alpha

VCAM-1:

Vascular cell adhesion molecule 1 (CD106)

References

  • Abraham EJ, Leech CA, Lin JC, Zulewski H, Habener JF (2002) Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells. Endocrinology 143:3152–3161

    PubMed  CAS  Google Scholar 

  • Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822

    PubMed  CAS  Google Scholar 

  • Atouf F, Park CH, Pechhold K, Ta M, Choi Y, Lumelsky NL (2007) No evidence for mouse pancreatic beta-cell epithelial-mesenchymal transition in vitro. Diabetes 56:699–702

    PubMed  CAS  Google Scholar 

  • Baeyens L, De Breuck S, Lardon J, Mfopou JK, Rooman I, Bouwens L (2005) İn vitro generation of insulin-producing β cells from adult exocrine pancreatic cells. Diabetologia 48:49–57

    PubMed  CAS  Google Scholar 

  • Banerjee M, Bhonde RR (2003) Islet generation from intra islet precursor cells of diabetic pancreas: in vitro studies depicting in vivo differentiation. JOP 4:137–145

    PubMed  Google Scholar 

  • Bonner-Weir S, Deery D, Leahy JL, Weir GC (1989) Compensatory growth of pancreatic beta-cells in adults after short-term glucose infusion. Diabetes 38:49–53

    PubMed  CAS  Google Scholar 

  • Bonner-Weir S, Baxter LA, Schuppin GT, Smith FE (1993) A second pathway for regeneration of adult exocrine and endocrine pancreas. A possible recapitulation of embryonic development. Diabetes 42:1715–1720

    PubMed  CAS  Google Scholar 

  • Bonner-Weir S, Taneja M, Weir GC, Tatarkiewicz K, Song KH, Sharma A, O’Neil JJ (2000) In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 97:7999–8004

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bonner-Weir S, Toschi E, Inada A, Reitz P, Fonseca SY, Aye T, Sharma A (2004) The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr Diabetes 5:16–22

    PubMed  Google Scholar 

  • Bouwens L, Rooman I (2005) Regulation of pancreatic β-cell mass. Physiol Rev 85:1255–1270

    PubMed  CAS  Google Scholar 

  • Brelje TC, Scharp DW, Lacy PE, Ogren L, Talamantes F, Robertson M, Friesen HG, Sorenson RL (1993) Effect of homologous placenta lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy. Endocrinology 132:879–887

    PubMed  CAS  Google Scholar 

  • Cantenys D, Portha B, Dutrillaux MC, Hollande E, Roze C, Picon L (1981) Histogenesis of the endocrine pancreas in newborn rats after destruction by streptozotosin. An immunocytochemical study. Virchows Arch B Cell Pathol Incl Mol Pathol 35:109–122

    PubMed  CAS  Google Scholar 

  • Carlotti F, Zaldumbide A, Loomans CJ, van Rossenberg E, Engelse M, de Koning EJ, Hoeben RC (2010) Isolated human islets contain a distinct population of mesenchymal stem cells. Islets 2:164–173

    PubMed  Google Scholar 

  • Chan JL, Tang KC, Patel AP, Bonilla LM, Pierobon N, Ponzio NM, Rameshwar P (2006) Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 107:4817–4824

    PubMed Central  PubMed  CAS  Google Scholar 

  • Chang CJ, Yen ML, Chen YC, Chien CC, Huang HI, Bai CH, Yen BL (2006) Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-γ. Stem Cells 24:2466–2477

    PubMed  CAS  Google Scholar 

  • Chentoufi AA, Gaudreau S, Nguyen A, Sabha M, Amrani A, Elghazali G (2011) Type I diabetes-associated tolerogenic properties of interleukin-2. Clin Dev Immunol 2011:289343

    PubMed Central  PubMed  Google Scholar 

  • Choi Y, Ta M, Atouf F, Lumelsky N (2004) Adult pancreas generates multipotent stem cells and pancreatic and nonpancreatic progeny. Stem Cells 22:1070–1084

    PubMed  CAS  Google Scholar 

  • Comoli P, Ginevri F, Maccario R, Avanzini MA, Marconi M, Groff A, Cometa A, Cioni M, Porretti L, Barberi W, Frassoni F, Locatelli F (2008) Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol Dial Transplant 23:1196–1202

    PubMed  CAS  Google Scholar 

  • Cornelius JG, Tchemev V, Kao KJ, Peck AB (1997) İn vitro generation of islets in long-term cultures of pluripotent stem cells from adult mouse pancreas. Horm Metab Res 29:271–277

    PubMed  CAS  Google Scholar 

  • Davani B, Ikonomou L, Raaka BM, Geras-Raaka E, Morton RA, Marcus-Samuels B, Gershengorn MC (2007) Human islet-derived precursor cells are mesenchymal stromal cells that differentiate and mature to hormone-expressing cells in vivo. Stem Cells 25:3215–3222

    PubMed  CAS  Google Scholar 

  • De Haro-Hernandez R, Cabrera-Munoz L, Mendez JD (2004) Regeneration of beta-cells and neogenesis from small ducts or acinar cells promote recovery of endocrine pancreatic function in alloxan-treated rats. Arch Med Res 35:114–120

    PubMed  Google Scholar 

  • Demoulin JB, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J, Renauld JC (1996) A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9. Mol Cell Biol 16:4710–4716

    PubMed Central  PubMed  CAS  Google Scholar 

  • Desai BM, Oliver-Krasinski J, De Leon DD, Farzad C, Hong N, Leach SD, Stoffers DA (2007) Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regeneration. J Clin Invest 117:971–977

    PubMed Central  PubMed  CAS  Google Scholar 

  • Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843

    PubMed  Google Scholar 

  • Dichmann S, Herouy Y, Purlis D, Rheinen H, Gebicke-Harter P, Norgauer J (2001) Fractalkine induces chemotaxis and actin polymerization in human dendritic cells. Inflamm Res 50:529–533

    PubMed  CAS  Google Scholar 

  • Dor Y, Melton DA (2004) How important are adult stem cells for tissue maintenance? Cell Cycle 3:1104–1106

    PubMed  CAS  Google Scholar 

  • Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46

    PubMed  CAS  Google Scholar 

  • Duvillie B, Attali M, Aiello V, Quemeneur E, Scharfmann R (2003) Label-retaining cells in the rat pancreas: location and differentiation potential in vitro. Diabetes 52:2035–2042

    PubMed  CAS  Google Scholar 

  • Elsässer HP, Adler G, Kern HF (1986) Time course and cellular source of pancreatic regeneration following acute pancreatitis in the rat. Pancreas 1:421–429

    Google Scholar 

  • English K, Ryan JM, Tobin L, Murphy MJ, Barry FP, Mahon BP (2009) Cell contact, prostaglandin E 2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4 CD25 high forkhead box P3 regulatory T cells. Clin Exp Immunol 156:149–160

    PubMed Central  PubMed  CAS  Google Scholar 

  • Fernandes A, King LC, Guz Y, Stein R, Wright CV, Teitelman G (1997) Differentiation of new insulin-producing cells is induced by injury in adult pancreatic islets. Endocrinology 138:1750–1762

    PubMed  CAS  Google Scholar 

  • Finegood DT, Scaglia L, Bonner-Weir S (1995) Dynamics of beta-cell mass in the growing rat pancreas. Estimation with a simple mathematical model. Diabetes 44:249–256

    PubMed  CAS  Google Scholar 

  • Finegood DT, Weir GC, Bonner-Weir S (1999) Prior streptozotocin treatment does not inhibit pancreas regeneration after 90% pancreatectomy in rats. Am J Physiol 276:E822–E827

    PubMed  CAS  Google Scholar 

  • Fraticelli P, Sironi M, Bianchi G, D’Ambrosio D, Albanesi C, Stoppacciaro A, Chieppa M, Allavena P, Ruco L, Girolomoni G, Sinigaglia F, Vecchi A, Mantovani A (2001) Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses. J Clin Invest 107:1173–1181

    PubMed Central  PubMed  CAS  Google Scholar 

  • Gallo R, Gambelli F, Gava B, Sasdelli F, Tellone V, Masini M, Marchetti P, Dotta F, Sorrentino V (2007) Generation and expansion of multipotent mesenchymal progenitor cells from cultured human pancreatic islets. Cell Death Differ 14:1860–1871

    PubMed  CAS  Google Scholar 

  • Gao R, Ustinov J, Pulkkinen MA, Lundin K, Korsgren O, Otonkoski T (2003) Characterization of endocrine progenitor cells and critical factors for their differentiation in human adult pancreatic cell culture. Diabetes 52:2007–2015

    PubMed  CAS  Google Scholar 

  • Georgia S, Bhushan A (2004) Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J Clin Invest 114:963–968

    PubMed Central  PubMed  CAS  Google Scholar 

  • Gershengorn MC, Hardikar AA, Wei C, Geras-Raaka E, Marcus-Samuels B, Raaka BM (2004) Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells. Science 306:2261–2264

    PubMed  CAS  Google Scholar 

  • Gershengorn MC, Geras-Raaka E, Hardikar AA, Raaka BM (2005) Are better islet cell precursors generated by epithelial-to-mesenchymal transition? Cell Cycle 4(3):380–382

    PubMed  CAS  Google Scholar 

  • Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F (2005) Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105:2821–2827

    PubMed  CAS  Google Scholar 

  • Gmyr V, Kerr-Conte J, Belaich S, Vandewalle B, Leteurtre E, Vantyghem MC, Lecomte-Houcke M, Proye C, Lefebvre J, Pattou F (2000) Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans. Diabetes 49:1671–1680

    PubMed  CAS  Google Scholar 

  • Gong J, Zhang G, Tian F, Wang Y (2012) Islet-derived stem cells from adult rats participate in the repair of islet damage. J Mol Histol 43:745–750

    PubMed  CAS  Google Scholar 

  • Gu D, Sarvetnick N (1993) Epithelial cell proliferation and islet neogenesis in IFN-g transgenic mice. Development 118:33–46

    PubMed  CAS  Google Scholar 

  • Gu D, Lee MS, Krahl T, Sarvetnick N (1994) Transitional cells in the regenerating pancreas. Development 120:1873–1881

    PubMed  CAS  Google Scholar 

  • Gu D, Arnush M, Sarvetnick N (1997) Endocrine/exocrine intermediate cells in streptozotocin-treated Ins-IFN-gamma transgenic mice. Pancreas 15:246–250

    PubMed  CAS  Google Scholar 

  • Guo Z, Li H, Li X, Yu X, Wang H, Tang P, Mao N (2006) In vitro characteristics and in vivo immunosuppressive activity of compact bone-derived murine mesenchymal progenitor cells. Stem Cells 24:992–1000

    PubMed  Google Scholar 

  • Guz Y, Nasir I, Teitelman G (2001) Regeneration of pancreatic beta cells from intra-islet precursor cells in an experimental model of diabetes. Endocrinology 142:4956–4968

    PubMed  CAS  Google Scholar 

  • Haber PS, Keogh GW, Apte MV, Moran CS, Stewart NL, Crawford DH, Pirola RC, McCaughan GW, Ramm GA, Wilson JS (1999) Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis. Am J Pathol 155:1087–1095

    PubMed Central  PubMed  CAS  Google Scholar 

  • Hao E, Tyrberg B, Itkin-Ansari P, Lakey JR, Geron I, Monosov EZ, Barcova M, Mercola M, Levine F (2006) Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas. Nat Med 12:310–316

    PubMed  CAS  Google Scholar 

  • Hayek A, Beattie GM, Cirulli V, Lopez AD, Ricordi C, Rubin JS (1995) Growth factor/matrix-induced proliferation of human adult beta cells. Diabetes 44:1458–1460

    PubMed  CAS  Google Scholar 

  • Holland AM, Gonez LJ, Harrison LC (2004) Progenitor cells in the adult pancreas. Diabetes Metab Res Rev 20:13–27

    PubMed  Google Scholar 

  • Holland AM, Góñez LJ, Naselli G, Macdonald RJ, Harrison LC (2005) Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of β-cells in the adult pancreas. Diabetes 54:2586–2595

    PubMed  CAS  Google Scholar 

  • Ikejiri N (1990) The vitamin A-storing cells in the human and rat pancreas. Kurume Med J 37:67–81

    PubMed  CAS  Google Scholar 

  • Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105:4120–4126

    PubMed  CAS  Google Scholar 

  • Joglekar MV, Parekh VS, Hardikar AA (2007) New pancreas from old: microregulators of pancreas regeneration. Trends Endocrinol Metab 18:393–400

    PubMed  CAS  Google Scholar 

  • Karaoz E, Ayhan S, Gacar G, Aksoy A, Duruksu G, Okçu A, Demircan PC, Sariboyaci AE, Kaymaz F, Kasap M (2010a) Isolation and characterization of stem cells from pancreatic islet: pluripotency, differentiation potential and ultrastructural characteristics. Cytotherapy 12:288–302

    PubMed  CAS  Google Scholar 

  • Karaoz E, Genç ZS, Demircan PÇ, Aksoy A, Duruksu G (2010b) Protection of rat pancreatic islet function and viability by coculture with rat bone marrow-derived mesenchymal stem cells. Cell Death Dis 1:e36

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kem H, Logothetopoulos J (1970) Steroid diabetes in the guinea pig. Studies on islet-cell ultrastructure and regeneration. Diabetes 19:145–154

    Google Scholar 

  • Kim BM, Kim SY, Lee S, Shin YJ, Min BH, Bendayan M, Park IS (2006) Clusterin induces differentiation of pancreatic duct cells into insulin-secreting cells. Diabetologia 49:311–320

    PubMed  CAS  Google Scholar 

  • Kim J, Breunig MJ, Escalante LE, Bhatia N, Denu RA, Dollar BA, Stein AP, Hanson SE, Naderi N, Radek J, Haughy D, Bloom DD, Assadi-Porter FM, Hematti P (2012) Biologic and immunomodulatory properties of mesenchymal stromal cells derived from human pancreatic islets. Cytotherapy 14:925–935

    PubMed Central  PubMed  CAS  Google Scholar 

  • Klein D, Barbé-Tuana F, Pugliese A, Ichii H, Garza D, Gonzalez M, Molano RD, Ricordi C, Pastori RL (2005) A functional CD40 receptor is expressed in pancreatic beta cells. Diabetologia 48:268–276

    PubMed  CAS  Google Scholar 

  • Korcakova L (1971) Mitotic division and its significance for regeneration of granulated B-cells in the islets of Langerhans in allozan-diabetic rats. Folia Morphol (Praha) 19:24–30

    CAS  Google Scholar 

  • Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F (2003) Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 101:3722–3729

    PubMed  CAS  Google Scholar 

  • Kruse C, Birth M, Rohwedel J, Assmuth K, Goepel A, Wedel T (2004) Pluripotency of adult stem cells derived from human and rat pancreas. Appl Phys A 79:1617–1624

    CAS  Google Scholar 

  • Lacy PE, Davie JM, Finke EH (1979) Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS. Science 204:312–313

    PubMed  CAS  Google Scholar 

  • Lardon J, Huyens N, Rooman I, Bouwens L (2004) Exocrine cell transdifferentiation in dexamethasone-treated rat pancreas. Virchows Arch 444:61–65

    PubMed  Google Scholar 

  • Lechene de la Porte P, Iovanna J, Odaira C, Choux R, Sarles H, Berger Z (1991) Involvement of tubular complexes in pancreatic regeneration after acute necrohemorrhagic pancreatitis. Pancreas 6:298–306

    PubMed  CAS  Google Scholar 

  • Lechner A, Habener JF (2003) Stem/progenitor cells derived from adult tissues: potential for the treatment of diabetes mellitus. Am J Physiol Endocrinol Metab 284:E259–E266

    PubMed  CAS  Google Scholar 

  • Lechner A, Leech CA, Abraham EJ, Nolan AL, Habener JF (2002) Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter. Biochem Biophys Res Commun 293:670–674

    PubMed  CAS  Google Scholar 

  • Lechner A, Nolan AL, Blacken RA, Habener JF (2005) Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue. Biochem Biophys Res Commun 327:581–588

    PubMed  CAS  Google Scholar 

  • Lei J, Cheng J, Li Y, Li S, Zhang L (2005) CD80, but not CD86, express on cultured murine keratinocyte stem cells. Transplant Proc 37:289–291

    PubMed  CAS  Google Scholar 

  • Leng SH, Lu FE (2005) Induction of pancreatic duct cells of neonatal rats into insulin-producing cells with fetal bovine serum: a natural protocol and its use for patch clamp experiments. World J Gastroenterol 11:6968–6974

    PubMed  Google Scholar 

  • Linning KD, Tai MH, Madhukar BV, Chang CC, Reed DN Jr, Ferber S, Trosko JE, Olson LK (2004) Redox-mediated enrichment of self-renewing adult human pancreatic cells that possess endocrine differentiation potential. Pancreas 29:e64–e76

    PubMed  Google Scholar 

  • Lipsett M, Finegood DT (2002) Beta-cell neogenesis during prolonged hyperglycemia in rats. Diabetes 51:1834–1841

    PubMed  CAS  Google Scholar 

  • List JF, Habener JF (2004) Glucagon-like peptide 1 agonists and the development and growth of pancreatic beta-cells. Am J Physiol Endocrinol Metab 286:E875–E881

    PubMed  CAS  Google Scholar 

  • Logothetopoulos J, Bell EG (1966) Histological and autoradiographic studies of the islets of mice injected with insulin antibody. Diabetes 15:205–211

    PubMed  CAS  Google Scholar 

  • Marynissen G, Aerts L, Van Assche FA (1983) The endocrine pancreas during pregnancy and lactation in the rat. J Dev Physiol 5:373–381

    PubMed  CAS  Google Scholar 

  • Means AL, Meszoely IM, Suzuki K, Miyamoto Y, Rustgi AK, Coffey RJ Jr, Wright CV, Stoffers DA, Leach SD (2005) Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. Development 132:3767–3776

    PubMed  CAS  Google Scholar 

  • Meier JJ, Ritzel RA, Maedler K, Gurlo T, Butler PC (2006) Increased vulnerability of newly forming beta cells to cytokine-induced cell death. Diabetologia 49:83–89

    PubMed  CAS  Google Scholar 

  • Meneilly GS, McIntosh CH, Pederson RA, Habener JF, Gingerich R, Egan JM, Finegood DT, Elahi D (2001) Effect of glucagon-like peptide 1 on non-insulin-mediated glucose uptake in the elderly patient with diabetes. Diabetes Care 24:1951–1956

    PubMed  CAS  Google Scholar 

  • Meneilly GS, Greig N, Tildesley H, Habener JF, Egan JM, Elahi D (2003a) Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes. Diabetes Care 26:2835–2841

    PubMed  CAS  Google Scholar 

  • Meneilly GS, McIntosh CH, Pederson RA, Habener JF, Ehlers MR, Egan JM, Elahi D (2003b) Effect of glucagon-like peptide 1 (7–36 amide) on insulin-mediated glucose uptake in patients with type 1 diabetes. Diabetes Care 26:837–842

    PubMed  CAS  Google Scholar 

  • Minami K, Okuno M, Miyawaki K, Okumachi A, Ishizaki K, Oyama K, Kawaguchi M, Ishizuka N, Iwanaga T, Seino S (2005) Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells. Proc Natl Acad Sci U S A 102:15116–15121

    PubMed Central  PubMed  CAS  Google Scholar 

  • Montanucci P, Pennoni I, Pescara T, Blasi P, Bistoni G, Basta G, Calafiore R (2011) The functional performance of microencapsulated human pancreatic islet-derived precursor cells. Biomaterials 32:9254–9262

    PubMed  CAS  Google Scholar 

  • Morandi F, Raffaghello L, Bianchi G, Meloni F, Salis A, Millo E, Ferrone S, Barnaba V, Pistoia V (2008) Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T-cell responses against viral or tumor-associated antigens. Stem Cells 26:1275–1287

    PubMed Central  PubMed  CAS  Google Scholar 

  • Morton RA, Geras-Raaka E, Wilson LM, Raaka BM, Gershengorn MC (2007) Endocrine precursor cells from mouse islets are not generated by epithelial-to-mesenchymal transition of mature beta cells. Mol Cell Endocrinol 270:87–93

    PubMed Central  PubMed  CAS  Google Scholar 

  • Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE (2006) Mesenchymal stem cells inhibit generation and function of both CD34+−derived and monocyte-derived dendritic cells. J Immunol 177:2080–2087

    PubMed  CAS  Google Scholar 

  • Nir T, Dor Y (2005) How to make pancreatic beta cells – prospects for cell therapy in diabetes. Curr Opin Biotechnol 16:524–529

    PubMed  CAS  Google Scholar 

  • Nishimura M, Umehara H, Nakayama T, Yoneda O, Hieshima K, Kakizaki M, Dohmae N, Yoshie O, Imai T (2002) Dual functions of fractalkine/CX3C ligand 1 in trafficking of perforin+/granzyme B+ cytotoxic effector lymphocytes that are defined by CX3CR1 expression. J Immunol 168:6173–6180

    PubMed  CAS  Google Scholar 

  • Noel D, Djouad F, Bouffı C, Mrugala D, Jorgensen C (2007) Multipotent mesenchymal stromal cells and immune tolerance. Leuk Lymphoma 48:1283–1289

    PubMed  CAS  Google Scholar 

  • Ogata T, Li L, Yamada S, Yamamoto Y, Tanaka Y, Takei I, Umezawa K, Kojima I (2004) Promotion of β-cell differentiation by conophylline in fetal and neonatal rat pancreas. Diabetes 53:2596–2602

    PubMed  CAS  Google Scholar 

  • Okuno M, Minami K, Okumachi A, Miyawaki K, Yokoi N, Toyokuni S, Seino S (2007) Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes. Am J Physiol Endocrinol Metab 292:E158–E165

    PubMed  CAS  Google Scholar 

  • Otonkoski T, Beattie GM, Rubin JS, Lopez AD, Baird A, Hayek A (1994) Hepatocyte growth factor/scatter factor has insulinotropic activity in human fetal pancreatic cells. Diabetes 43:947–953

    PubMed  CAS  Google Scholar 

  • Ouziel-Yahalom L, Zalzman M, Anker-Kitai L, Knoller S, Bar Y, Glandt M, Herold K, Efrat S (2006) Expansion and redifferentiation of adult human pancreatic islet cells. Biochem Biophys Res Commun 341:291–298

    PubMed  CAS  Google Scholar 

  • Oyama K, Minami K, Ishizaki K, Fuse M, Miki T, Seino S (2006) Spontaneous recovery from hyperglycemia by regeneration of pancreatic β-cells in Kir6.2G132S transgenic mice. Diabetes 55:1930–1938

    PubMed  CAS  Google Scholar 

  • Peck AB, Cornelius JG (1995) İn vitro growth of mature pancreatic islets of Langerhans from single, pluripotent stem cells isolated from pre-diabetic adult pancreas. Diabetes 44:10A

    Google Scholar 

  • Peck AB, Ramiya V (2004) İn vitro-generation of surrogate islets from adult stem cells. Transpl Immunol 12:259–272

    PubMed  CAS  Google Scholar 

  • Petropavlovskaia M, Rosenberg L (2002) Identification and characterization of small cells in the adult pancreas: potential progenitor cells? Cell Tissue Res 310:51–58

    PubMed  Google Scholar 

  • Poliakova L, Pirone A, Farese A, MacVittie T, Farney A (2004) Presence of nonhematopoietic side population cells in the adult human and nonhuman primate pancreas. Transplant Proc 36:1166–1168

    PubMed  CAS  Google Scholar 

  • Rabinovitch A, Suarez-Pinzon WL, Shapiro AM, Rajotte RV, Power R (2002) Combination therapy with sirolimus and interleukin-2 prevents spontaneous and recurrent autoimmune diabetes in NOD mice. Diabetes 51:638–645

    PubMed  CAS  Google Scholar 

  • Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG (2000) Reversal of insulin dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 6:278–282

    PubMed  CAS  Google Scholar 

  • Rao MS, Dwivedi RS, Yeldandi AV, Subbarao V, Tan XD, Usman MI, Thangada S, Nemali MR, Kumar S, Scarpelli DG, Reddy JK (1989) Role of periductal and ductular epithelial cells of the adult rat pancreas in pancreatic hepatocyte lineage. A change in the differentiation commitment. Am J Pathol 134:1069–1086

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rasmusson I (2006) Immun modulation by mesenchymal stem cells. Exp Cell Res 312:2169–2179

    PubMed  CAS  Google Scholar 

  • Rooman I, Bouwens L (2004) Combined gastrin and epidermal growth factor treatment induces islet regeneration and restores normoglycaemia in C57Bl6/J mice treated with alloxan. Diabetologia 47:259–265

    PubMed  CAS  Google Scholar 

  • Rosenberg L (1998) Induction of islet cell neogenesis in the adult pancreas: the partial duct obstruction model. Microsc Res Tech 43:337–346

    PubMed  CAS  Google Scholar 

  • Rosenberg L, Vinik AL (1992) Trophic stimulation of the ductular-islet cell axis: a new approach to the treatment of diabetes. Adv Exp Med Biol 321:95–104

    PubMed  CAS  Google Scholar 

  • Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC (1990) Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 61:1121–1135

    PubMed  CAS  Google Scholar 

  • Saotome T, Inoue H, Fujimiya M, Fujiyama Y, Bamba T (1997) Morphological and immunocytochemical identification of periacinar fibroblast-like cells derived from human pancreatic acini. Pancreas 14:373–382

    PubMed  CAS  Google Scholar 

  • Schmied BM, Ulrich A, Matsuzaki H, Ding X, Ricordi C, Weide L, Moyer MP, Batra SK, Adrian TE, Pour PM (2001) Transdifferentiation of human islet cells in a long-term culture. Pancreas 23:157–171

    PubMed  CAS  Google Scholar 

  • Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22:1115–1124

    PubMed  CAS  Google Scholar 

  • Sharma A, Zangen DH, Reitz P, Taneja M, Lissauer ME, Miller CP, Weir GC, Habener JF, Bonner-Weir S (1999) The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration. Diabetes 48:507–513

    PubMed  CAS  Google Scholar 

  • Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 111:1327–1333

    PubMed  CAS  Google Scholar 

  • Sphyris N, Logsdon CD, Harrison DJ (2005) Improved retention of zymogen granules in cultured murine pancreatic acinar cells and induction of acinar-ductal transdifferentiation in vitro. Pancreas 30:148–157

    PubMed  Google Scholar 

  • Stagg J, Pommey S, Eliopoulos N, Galipeau J (2006) Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell. Blood 107:2570–2577

    PubMed  CAS  Google Scholar 

  • Street CN, Sipione S, Helms L, Binette T, Rajotte RV, Bleackley RC, Korbutt GS (2004) Stem cell-based approaches to solving the problem of tissue supply for islet transplantation in type 1 diabetes. Int J Biochem Cell Biol 36:667–683

    PubMed  CAS  Google Scholar 

  • Suzuki A, Nakauchi H, Taniguchi H (2004) Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 53:2143–2152

    PubMed  CAS  Google Scholar 

  • Swenne I (1992) Pancreatic beta-cell growth and diabetes mellitus. Diabetologia 35:193–201

    PubMed  CAS  Google Scholar 

  • Tang Q, Adams JY, Penaranda C, Melli K, Piaggio E, Sgouroudis E, Piccirillo CA, Salomon BL, Bluestone JA (2008) Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 28:687–697

    PubMed Central  PubMed  CAS  Google Scholar 

  • von Mach MA, Hengstler JG, Brulport M, Eberhardt M, Schormann W, Hermes M, Prawitt D, Zabel B, Grosche J, Reichenbach A, Muller B, Weilemann LS, Zulewski H (2004) İn vitro cultured islet-derived progenitor cells of human origin express human albumin in severe combined immunodeficiency mouse liver in vivo. Stem Cells 22:1134–1141

    Google Scholar 

  • Wang RN, Kloppel G, Bouwens L (1995) Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia 38:1405–1411

    PubMed  CAS  Google Scholar 

  • Wang J, Song LJ, Gerber DA, Fair JH, Rice L, LaPaglia M, Andreoni KA (2004) A model utilizing adult murine stem cells for creation of personalized islets for transplantation. Transplant Proc 36:1188–1190

    PubMed  CAS  Google Scholar 

  • Wang ZV, Mu J, Schraw TD, Gautron L, Elmquist JK, Zhang BB, Brownlee M, Scherer PE (2008) PANIC-ATTAC: a mouse model for inducible and reversible β-cell ablation. Diabetes 57:2137–2148

    PubMed Central  PubMed  CAS  Google Scholar 

  • Watari N, Hotta Y, Mabuchi Y (1982) Morphological studies on a vitamin A-storing cell and its complex with macrophage observed in mouse pancreatic tissues following excess vitamin A administration. Okajimas Folia Anat Jpn 58:837–858

    PubMed  CAS  Google Scholar 

  • Weaver CV, Sorenson RL, Kaung HC (1985) Immunocytochemical localization of insulin-immunoreactive cells in the pancreatic ducts of rats treated with trypsin inhibitor. Diabetologia 28:781–785

    PubMed  CAS  Google Scholar 

  • Xu G, Stoffers DA, Habener JF, Bonner-Weir S (1999) Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats. Diabetes 48:2270–2276

    PubMed  CAS  Google Scholar 

  • Xu X, D’Hoker J, Stangé G, Bonné S, De Leu N, Xiao X, Van de Casteele M, Mellitzer G, Ling Z, Pipeleers D, Bouwens L, Scharfmann R, Gradwohl G, Heimberg H (2008) Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132:197–207

    PubMed  CAS  Google Scholar 

  • Yamamoto K, Miyagawa J, Waguri M, Sasada R, Igarashi K, Li M, Nammo T, Moriwaki M, Imagawa A, Yamagata K, Nakajima H, Namba M, Tochino Y, Hanafusa T, Matsuzawa Y (2000) Recombinant human betacellulin promotes the neogenesis of β-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion. Diabetes 49:2021–2027

    PubMed  CAS  Google Scholar 

  • Yamaoka T, Yoshino K, Yamada T, Idehara C, Hoque MO, Moritani M, Yoshimoto K, Hata J, Itakura M (2000) Diabetes and tumor formation in transgenic mice expressing Reg I. Biochem Biophys Res Commun 278:368–376

    PubMed  CAS  Google Scholar 

  • Ye Z, Wang Y, Xie HY, Zheng SS (2008) Immunosuppressive effects of rat mesenchymal stem cells: involvement of CD4+ CD25+ regulatory T cells. Hepatobiliary Pancreat Dis Int 7:608–614

    PubMed  Google Scholar 

  • Zhang L, Hong TP, Hu J, Liu YN, Wu YH, Li LS (2005) Nestin-positive progenitor cells isolated from human fetal pancreas have phenotypic markers identical to mesenchymal stem cells. World J Gastroenterol 11:2906–2911

    PubMed  CAS  Google Scholar 

  • Zheng SG, Wang JH, Koss MN, Quismorio F Jr, Gray JD, Horwitz DA (2004) CD4+ and CD8+ regulatory T cells generated ex-vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus host disease with lupus-like syndrome. J Immunol 172:1531–1539

    PubMed  CAS  Google Scholar 

  • Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455:627–632

    PubMed  CAS  Google Scholar 

  • Zimmermann A, Gloor B, Kappeler A, Uhl W, Friess H, Buchler MW (2002) Pancreatic stellate cells contribute to regeneration early after acute necrotising pancreatitis in humans. Gut 51:574–578

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB, Moritz W, Muller B, Vallejo M, Thomas MK, Habener JF (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50:521–533

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Stem Cell and Gene Therapies Research and Application, Kocaeli University, Kocaeli University Research Hospital C-Block, 41380, Kocaeli, Turkey

    Prof. Dr. Erdal Karaoz & Gokhan Duruksu

Authors
  1. Prof. Dr. Erdal Karaoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gokhan Duruksu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erdal Karaoz .

Editor information

Editors and Affiliations

  1. Södersjukhuset, Karolinska Institutet Dept. Clinical Research & Education, Stockholm, Sweden

    Md. Shahidul Islam

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Karaoz, E., Duruksu, G. (2013). Stem Cells in Pancreatic Islets. In: Islam, M. (eds) Islets of Langerhans, 2. ed.. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6884-0_31-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-6884-0_31-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-6884-0

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation