The Effect of Fetal Liver-Derived Cell Suspension Allotransplantation on Patients with Diabetes: First Year of Follow-up
Abstract
Stem cell-based therapies have recently opened up new horizons for treatment of various types of diseases including diabetes mellitus. However, long-term efficacy and safety of these novel modalities still remain a serious question. Hereby, we aim to report the one-year follow-up results in the diabetic patients who underwent fetal liver-derived hematopoietic stem cell allotransplantation. Fifty six patients with type one (n=30) and type two (n=26) diabetes, aged 10-58 years old (32.8 ± 16.3) were divided into the intervention and placebo group. The patients in the intervention group underwent fetal liver-derived hematopoietic stem cell transplantation while the patients in the placebo group received 5 ml of normal saline both via an intravenous route. The patients were visited at regular intervals to evaluate the efficacy of transplantation in glycemic control as well as possible complications. In the 6th month of the follow-up, there was a significant decrease in HbA1c levels in all groups without any rise in the fasting c-peptide. However, none of the precipitants transiently or continuously became insulin free in the first year after transplantation. It can be concluded that, in this study, fetal liver-derived hematopoietic stem cell transplantation had no significant effects on glycemic control. The heterogeneity of our patients might account for the negative results. Hence, longer follow-up results will be reported in the near future.
Roep BO, Peakman M. Surrogate end points in the design of immunotherapy trials: emerging lessons from type 1 diabetes. Nat Rev Immunol 2010;10(2):145-52.
Narendran P, Estella E, Fourlanos S. Immunology of type
diabetes. QJM 2005;98(8):547-56.
Rewers M, Gottlieb P. Immunotherapy for the prevention and treatment of type 1 diabetes: human trials and a lookinto the future. Diabetes Care 2009;32(10):1769-82.
Bergman RN, Finegood DT, Kahn SE. The evolution of beta-cell dysfunction and insulin resistance in type 2 diabetes. Eur J Clin Invest 2002;32 (Suppl 3):35-45.
Fernández-Real JM, Pickup JC. Innate immunity, insulin resistance and type 2 diabetes. Trends Endocrinol Metab 2008;19(1):10-6.
Fernández-Real JM, Pickup JC. Innate immunity, insulin resistance and type 2 diabetes. Diabetologia 2012;55(2):273-8.
Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006;17(1):4-12.
Schertzer JD, Tamrakar AK, Magalhães JG, Pereira S, Bilan PJ, Fullerton MD, Liu Z, Steinberg GR, Giacca A, Philpott DJ, Klip A. NOD1 activators link innate immunity to insulin resistance. Diabetes 2011;60(9):2206-15.
Naik RG, Brooks-Worrell BM, Palmer JP. Latentautoimmune diabetes in adults. J Clin Endocrinol Metab 2009;94(12):4635-44.
Zatz M. Stem cell researches in Brazil: present and future challenges. Stem Cell Rev 2009;5(2):123-9.
Larijani B, Esfahani EN, Amini P, Nikbin B, Alimoghaddam K, Amiri S, Malekzadeh R, Yazdi NM, Ghodsi M, Dowlati Y, Sahraian MA, Ghavamzadeh A. Stem cell therapy in treatment of different diseases. Acta Med Iran 2012;50(2):79-96.
Blyszczuk P, Czyz J, Kania G, Wagner M, Roll U, St- Onge L, Wobus AM. Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci U S A 2003;100(3):998-1003.
Miyazaki S, Yamato E, Miyazaki J. Regulated expression of pdx-1 promotes in vitro differentiation of insulinproducingcells from embryonic stem cells. Diabetes2004;53(4):1030-7.
Hori Y, Rulifson IC, Tsai BC, Heit JJ, Cahoy JD, Kim SK.Growth inhibitors promote differentiation of insulinproducing tissue from embryonic stem cells. Proc Natl Acad Sci U S A 2002;99(25):16105-10.
Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets.Science 2001;292(5520):1389-94.
Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, D'Amour KA, CarpenterMK, Baetge EE. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulinsecreting cells in vivo. Nat Biotechnol 2008;26(4):443-52.
Burt RK, Testori A, Craig R, Cohen B, Suffit R, Barr W. Hematopoietic stem cell transplantation for autoimmune diseases: what have we learned? J Autoimmun 2008;30(3):116-20.
Rosengren AH, Renström E. Autologous hematopoietic stem cell transplantation in type 1-diabetes. Islets2009;1(1):81-3.
Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC,Moraes DA, Pieroni F, Coutinho M, Malmegrim KC,Foss-Freitas MC, Simões BP, Foss MC, Squiers E, Burt RK. Autologous nonmyeloablative hematopoietic stem celltransplantation in newly diagnosed type 1 diabetesmellitus. JAMA 2007;297(14):1568-76.
Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simões BP, Martinez EZ, Foss MC, Burt RK,Voltarelli JC. C-peptide levels and insulin independencefollowing autologous nonmyeloablative hematopoieticstem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 2009;301(15):1573-9.
Bhansali A, Upreti V, Khandelwal N, Marwaha N, GuptaV, Sachdeva N, Sharma RR, Saluja K, Dutta P, Walia R, Minz R, Bhadada S, Das S, Ramakrishnan S. Efficacy ofautologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cells Dev 2009;18(10):1407-16.
Marcus AJ, Woodbury D. Fetal stem cells from extraembryonic tissues: do not discard. J Cell Mol Med 2008;12(3):730-42.
O'Donoghue K, Fisk NM. Fetal stem cells. Best Pract Res Clin Obstet Gynaecol 2004;18(6):853-75.
Hess PG. Risk of tumorigenesis in first-in-human trials of embryonic stem cell neural derivatives: Ethics in the faceof long-term uncertainty. Account Res 2009;16(4):175-98.
Mayhew CN, Wells JM. Converting human pluripotent stem cells into beta-cells: recent advances and future challenges. Curr Opin Organ Transplant 2010;15(1):54-60.
Watt FM, Driskell RR. The therapeutic potential of stemcells. Philos Trans R Soc Lond B Biol Sci 2010;365(1537):155-63.
Denker HW. Induced pluripotent stem cells: how to deal with the developmental potential. Reprod Biomed Online 2009;19 Suppl 1:34-7.
Fiorina P, Jurewicz M, Augello A, Vergani A, Dada S, La Rosa S, Selig M, Godwin J, Law K, Placidi C, Smith RN, Capella C, Rodig S, Adra CN, Atkinson M, Sayegh MH, etal. Immunomodulatory function of bone marrow-derivedmesenchymal stem cells in experimental autoimmune type1 diabetes. J Immunol 2009;183(2):993-1004.
Couri CE, Voltarelli JC. Potential role of stem cell therapy in type 1 diabetes mellitus. Arq Bras Endocrinol Metabol 2008;52(2):407-15.
Götherström C, Ringdén O, Tammik C, Zetterberg E,Westgren M, Le Blanc K. Immunologic properties of human fetal mesenchymal stem cells. Am J Obstet Gynecol 2004;190(1):239-45.
Lewis JA, Jonsson B, Kreutz G, Sampaio C, van Zwieten- Boot B. Placebo-controlled trials and the Declaration of Helsinki. Lancet 2002;359(9314):1337-40.
Rickham PP: Human experimentation. code of ethics ofthe world medical association. Declaration of Helsinki. BrMed J 1964;2(5402):177.
Saniei M, De Vries R. Embryonic stem cell research in Iran: status and ethics. Indian J Med Ethics 2008;5(4):181-4.
Arjmand B, Aghayan HR, Nasli-Esfahani E, et al: Clinicalisolation and purification of fetal hematopoietic stem cells= for treatment of diabetes mellitus. Rev Diabet Stud 2011;8:174
Kromer P, Korzeniowska-Kromer E. Anal canal development in the embryonic and early foetal period. Folia Morphol (Warsz) 2003;62(3):285-7.
Waldron-Lynch F, Herold KC. Advances in Type 1 diabetes therapeutics: immunomodulation and beta-cell salvage. Endocrinol Metab Clin North Am 2009;38(2):303-17, viii.
Palmer JP. C-peptide in the natural history of type 1diabetes. Diabetes Metab Res Rev 2009;25(4):325-8.
Voltarelli JC, Couri CEB. Stem cell transplantation for type 1 diabetes mellitus. Diabetol Metab Syndr 2009;1:4.
Le Blanc K, Ringdén O. Mesenchymal stem cells:properties and role in clinical bone marrow transplantation. Curr Opin Immunol 2006;18(5):586-91.
Thirabanjasak D, Tantiwongse K, Thorner PS. Angiomyeloproliferative lesions following autologous stem cell therapy. J Am Soc Nephrol 2010;21(7):1218-22.
Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, Paz N, Koren-Michowitz M, Waldman D, Leider-Trejo L, Toren A, Constantini S, Rechavi G. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 2009;6(2):e1000029.
Files | ||
Issue | Vol 50, No 8 (2012) | |
Section | Original Article(s) | |
Keywords | ||
Diabetes mellitus Fetal hematopoietic stem cells Cell therapy |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |