期刊论文详细信息
Journal of Biomedical Science
Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats
Tien-Hua Chen5  Jia-Fwu Shyu3  Ling-Chen Tai5  Zen-Chung Weng4  Yi-Ming Shyr5  Hwai-Shi Wang1  Pei-Jiun Tsai2 
[1] Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, 201 Shih-Pai Road Section 2, Taipei, 112, Republic of China;Department of Emergency, Division of Surgery, Veteran General Hospital, Taipei, Republic of China;Department of Biology and Anatomy, National Defense Medical Center, 161 Ming Chuan E. Road Section 6, Taipei, 114, Republic of China;Division of Cardiovascular Surgery, Cardiovascular Center, Taipei Medical University Hospital, Taipei, Republic of China;Department of Surgery, Veteran General Hospital, Taipei, Republic of China
关键词: Transplant;    Insulin-producing cells;    Portal vein;    Mesenchymal stem cell;   
Others  :  825116
DOI  :  10.1186/1423-0127-19-47
 received in 2012-02-11, accepted in 2012-04-30,  发布年份 2012
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【 摘 要 】

Background

Although diabetes mellitus (DM) can be treated with islet transplantation, a scarcity of donors limits the utility of this technique. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord could be induced efficiently to differentiate into insulin-producing cells. Secondly, we evaluated the effect of portal vein transplantation of these differentiated cells in the treatment of streptozotocin-induced diabetes in rats.

Methods

MSCs from human umbilical cord were induced in three stages to differentiate into insulin-producing cells and evaluated by immunocytochemistry, reverse transcriptase, and real-time PCR, and ELISA. Differentiated cells were transplanted into the liver of diabetic rats using a Port-A catheter via the portal vein. Blood glucose levels were monitored weekly.

Results

Human nuclei and C-peptide were detected in the rat liver by immunohistochemistry. Pancreatic β-cell development-related genes were expressed in the differentiated cells. C-peptide release was increased after glucose challenge in vitro. Furthermore, after transplantation of differentiated cells into the diabetic rats, blood sugar level decreased. Insulin-producing cells containing human C-peptide and human nuclei were located in the liver.

Conclusion

Thus, a Port-A catheter can be used to transplant differentiated insulin-producing cells from human MSCs into the portal vein to alleviate hyperglycemia among diabetic rats.

【 授权许可】

   
2012 Tsai et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Bottazzo GF, Florin-Christensen A, Doniach D: Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 1974, 2:1279-1283.
  • [2]Gepts W: Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 1965, 14:619-633.
  • [3]Larsen JL: Pancreas transplantation: indications and consequences. Endocr Rev 2004, 25:919-946.
  • [4]Ryan EA, Lakey JR, Rajotte RV, Korbutt GS, Kin T, Imes S, Rabinovitch A, Elliott JF, Bigam D, Kneteman NM, Warnock GL, Larsen I, Shapiro AM: Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes 2001, 50:710-719.
  • [5]Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Eng J Med 2000, 343:230-238.
  • [6]Yamaoka T: Regeneration therapy of pancreatic beta cells: towards a cure for diabetes? Biochem Biophys Res Commun 2002, 296:1039-1043.
  • [7]Matsumoto S, Noguchi H, Hatanaka N, Shimoda M, Kobayashi N, Jackson A, Onaca N, Naziruddin B, Levy MF: Estimation of donor usability for islet transplantation in the United States with the kyoto islet isolation method. Cell Transplant 2009, 18:549-556.
  • [8]Kobayashi N, Yuasa T, Okitsu T: Regenerative medicine for diabetes mellitus. Cell Transplant 2009, 18:491-496.
  • [9]Friedenstein AJ, Piatetzky S, Petrakova KV: Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 1966, 16:381-390.
  • [10]Lennon DP, Edmison JM, Caplan AI: Cultivation of rat marrow-derived mesenchymal stem cells in reduced oxygen tension: effects on in vitro and in vivo osteochondrogenesis. J Cell Physiol 2001, 187:345-355.
  • [11]Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284:143-147.
  • [12]Sekiya I, Vuoristo JT, Larson BL, Prockop DJ: In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis. Proc Natl Acad Sci U S A 2002, 99:4397-4402.
  • [13]Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A: Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 2003, 425:968-973.
  • [14]Fukuda K: Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering. Artif Organs 2001, 25:187-193.
  • [15]Hakuno D, Fukuda K, Makino S, Konishi F, Tomita Y, Manabe T, Suzuki Y, Umezawa A, Ogawa S: Bone marrow-derived regenerated cardiomyocytes (CMG Cells) express functional adrenergic and muscarinic receptors. Circulation 2002, 105:380-386.
  • [16]Orlic D: Adult bone marrow stem cells regenerate myocardium in ischemic heart disease. Ann N Y Acad Sci 2003, 996:152-157.
  • [17]Jiang J, Au M, Lu K, Eshpeter A, Korbutt G, Fisk G, Majumdar AS: Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 2007, 25:1940-1953.
  • [18]Pereira RF, Hume EL, Halford KW, Prockop DJ: Bone fragility in transgenic mice expressing a mutated gene for type I procollagen (COL1A1) parallels the age-dependent phenotype of human osteogenesis imperfecta. J Bone Miner Res 1995, 10:1837-1843.
  • [19]Pereira RF, O’Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K, Prockop DJ: Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc Natl Acad Sci U S A 1998, 95:1142-1147.
  • [20]Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F: Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998, 279:1528-1530.
  • [21]Pereira RF, Halford KW, O’Hara MD, Leeper DB, Sokolov BP, Pollard MD, Bagasra O, Prockop DJ: Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A 1995, 92:4857-4861.
  • [22]Spees JL, Olson SD, Ylostalo J, Lynch PJ, Smith J, Perry A, Peister A, Wang MY, Prockop DJ: Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc Natl Acad Sci U S A 2003, 100:2397-2402.
  • [23]Karnieli O, Izhar-Prato Y, Bulvik S, Efrat S: Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells 2007, 25:2837-2844.
  • [24]Chandra V, Phadnis S, Nair PD, Bhonde RR: Generation of pancreatic hormone-expressing islet-like cell aggregates from murine adipose tissue-derived stem cells. Stem Cells 2009, 27:1941-1953.
  • [25]Parekh VS, Joglekar MV, Hardikar AA: Differentiation of human umbilical cord blood-derived mononuclear cells to endocrine pancreatic lineage. Differentiation 2009, 78:232-240.
  • [26]Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC: Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 2004, 22:1330-1337.
  • [27]Wang HS, Shyu JF, Shen WS, Hsu HC, Chi TC, Chen CP, Huang SW, Shyr YM, Tang KT, Chen TH: Transplantation of insulin producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice. Cell Transplant 2011, 20(3):455-466.
  • [28]Suen PM, Li K, Chan JC, Leung PS: In vivo treatment with glucagon-like peptide 1 promotes the graft function of fetal islet-like cell clusters in transplanted mice. Int J Biochem Cell Biol 2006, 38:951-960.
  • [29]Banerjee M, Kumar A, Bhonde RR: Reversal of experimental diabetes by multiple bone marrow transplantation. Biochem Biophys Res Commun 2005, 328:318-325.
  • [30]Hussain MA, Theise ND: Stem-cell therapy for diabetes mellitus. Lancet 2004, 364:203-205.
  • [31]Serup P, Madsen OD, Mandrup-Poulsen T: Islet and stem cell transplantation for treating diabetes. BMJ 2001, 322:29-32.
  • [32]Siminovitch L, McCulloch EA, Till JE: The distribution of colony-forming cells among Spleen colonies. J Cell Physiol 1963, 62:327-336.
  • [33]Yoshida S, Ishikawa F, Kawano N, Shimoda K, Nagafuchi S, Shimoda S, Yasukawa M, Kanemaru T, Ishibashi H, Shultz LD, Harada M: Human cord blood–derived cells generate insulin-producing cells in vivo. Stem Cells 2005, 23:1409-1416.
  • [34]Hansson M, Tonning A, Frandsen U, Petri A, Rajagopal J, Englund MC, Heller RS, Hakansson J, Fleckner J, Skold HN, Melton D, Semb H, Serup P: Artifactual insulin release from differentiated embryonic stem cells. Diabetes 2004, 53:2603-2609.
  • [35]Ryu S, Kodama S, Ryu K, Schoenfeld DA, Faustman DL: Reversal of established autoimmune diabetes by restoration of endogenous beta cell function. J Clin Invest 2001, 108:63-72.
  • [36]Shah R, Jindal RM: Reversal of diabetes in the rat by injection of hematopoietic stem cells infected with recombinant adeno-associated virus containing the preproinsulin II gene. Pancreatology 2003, 3:422-428.
  • [37]Golosow N, Grobstein C: Epitheliomesenchymal interaction in pancreatic morphogenesis. Dev Biol 1962, 4:242-255.
  • [38]Rajagopal J, Anderson WJ, Kume S, Martinez OI, Melton DA: Insulin staining of ES cell progeny from insulin uptake. Science 2003, 299:363.
  • [39]Lopez-Talavera JC, Garcia-Ocana A, Sipula I, Takane KK, Cozar-Castellano I, Stewart AF: Hepatocyte growth factor gene therapy for pancreatic islets in diabetes: reducing the minimal islet transplant mass required in a glucocorticoid-free rat model of allogeneic portal vein islet transplantation. Endocrinology 2004, 145:467-474.
  • [40]McEvoy RC, Hegre OD: Syngeneic transplantation of fetal rat pancreas. III. Effect of insulin treatment on the growth and differentiation of the pancreatic implants after reversal of diabetes. Diabetes 1979, 28:141-146.
  • [41]Chao KC, Chao KF, Fu YS, Liu SH: Islet-like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One 2008, 1:e1451.
  • [42]Beattie GM, Lopez AD, Otonkoski T, Hayek A: Transplantation of human fetal pancreas: fresh vs. cultured fetal islets or ICCS. J Mol Med 1999, 77:70-73.
  • [43]Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F: Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 2000, 49:157-162.
  • [44]Liu JC, Tseng HS, Chen CY, Chern MS, Chang CY: Percutaneous retrieval of 20 centrally dislodged Port-A catheter fragments. Clin Imaging 2004, 28:223-229.
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