C-peptide increase in chronic type 1 diabetic patients treated with autologous bone marrow cell transplantation through pancreatic artery catheterization: Three years follow-up


Background: Recent extensive clinical evidence demonstrated that autologous adult stem cell therapy was safe and effective as a treatment strategy for type 1 diabetes. Our initial work was designed to examine the safety and efficacy of the implantation technique on 20 subjects with six months of evolution. This new report analyzes the results from three years follow up. Methods: With the authorization from the Ministry of Health of Argentina, 20 subjects with type 1 diabetes were treated with single autologous bone marrow cell transplantation into pancreatic blood flow through pancreatic artery catheterization immediately after bone marrow aspiration. The primary endpoint was defined as normalization of C-peptide and glycated hemoglobin (HbA1c) with insulin independence at 3 years posttreatment. Results: 15 subjects (75%) achieved clinical improvements. 7 subjects (33%) reached the primary endpoint, in which 4 subjets with decreased C-peptide levels required insulin administration again at 3 years post-treatment. Other 8 subjects (34%) showed partial function at 3 years post-treatment. There were no serious adverse events observed. No increases of islet cell antibody (ICA) and glutamic acid decarboxylase (GAD) antibody. Conclusion: This procedure may be a safe and effective treatment for chronic type 1 diabetes. The follow-up results showed a significant increase of the pancreatic secretion of C-peptide and a decrease in the daily dose of exogenous insulin. This effect partially disappears by the three years follow-up without an increase of the level of the ICA and GAD antibodies.

Share and Cite:

Mesples, A. , Jiang, S. , Zhang, Y. , Luo, Z. and Hu, X. (2013) C-peptide increase in chronic type 1 diabetic patients treated with autologous bone marrow cell transplantation through pancreatic artery catheterization: Three years follow-up. Stem Cell Discovery, 3, 56-63. doi: 10.4236/scd.2013.31009.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Gianani, R., Campbell-Thompson, M., Sarkar, S.A., et al. (2010) Dimorphic histopathology of long-standing childhood-onset diabetes. Diabetologia, 53, 690-698. doi:10.1007/s00125-009-1642-y
[2] Madsbad, S., Krarup, T., Regeur, L., Faber, O.K. and Binder, C. (1980) Insulin secretory reserve in insulin dependent patients at time of diagnosis and the first 180 days of insulin treatment. Acta Endocrinologica, 95, 359-363.
[3] Steele, C., Hagopian, W.A., Gitelman, S., et al. (2004) Insulin secretion in type 1 diabetes. Diabetes, 53, 426-433. doi:10.2337/diabetes.53.2.426
[4] Eff, Ch., Faber, O. and Deckert, T. (1978) Persistent insulin secretion, assessed by plasma C-peptide estimation in long-term juvenile diabetics with a low insulin requirement. Diabetologia, 15, 169-172. doi:10.1007/BF00421234
[5] Nakanishi, K. and Watanabe, C. (2008) Rate of b-cell destruction in type 1 diabetes influences the development of diabetic retinopathy: protective effect of residual b-cell function for more than 10 years. The Journal of Clinical Endocrinology & Metabolism, 93, 4759-4766. doi:10.1210/jc.2008-1209
[6] Liu, E.H., Digon, B.J., Hirshberg, B., et al. (2009) Pancreatic beta cell function persists in many patients with chronic type 1 diabetes, but is not dramatically improved by prolonged immunosuppression and euglycaemia from a beta cell allograft. Diabetologia, 52, 1369-1380. doi:10.1007/s00125-009-1342-7
[7] Madsbad, S., Faber, O.K., Binder, C., McNair, P., Christiansen, C. and Transb?l, I. (1978) Prevalence of residual beta-cell function in insulin dependent diabetics in relation to age at onset and duration of diabetes. Diabetes, 27, 262-264.
[8] Ramiya, V.K., Maraist, M., Arfors, K.E., Schatz, D.A., Peck, A.B. and Cornelius, J.G. (2000) Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nature Medicine, 6, 278-282. doi:10.1038/73128
[9] Dor, Y., Brown, J., Martinez, O.I. and Melton, D.A. (2004) Adult pancreatic-cells are formed by self-duplication rather than stem-cell differentiation. Nature, 429, 41-46. doi:10.1038/nature02520
[10] de la Tour, D., Halvorsen, T., Demeterco, C., Tyrberg, B., Itkin-Ansari, P., Loy, M., Loo, S.J., Hao, E., Bossie, S. and Levine, F. (2001) Beta-cell differentiation from a human pancreatic cell line in vitro and in vivo. Molecular Endocrinology, 15, 476-483. doi:10.1210/me.15.3.476
[11] Chen, L.B., Jiang, X.B. and Yang, L. (2004) Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World Journal of Gastroenterology, 10, 3016-3020.
[12] Venstrom, J.M., McBride, M.A., Rother, K.I., Hirshberg, B., Orchard, T.J. and Harlan, D.M. (2003) Survival after pancreas transplantation in subjects with diabetes and preserved kidney function. JAMA, 290, 2817-2823. doi:10.1001/jama.290.21.2817
[13] Shapiro, A.M.J., Ricordi, C., Hering, B.J., Auchincloss, H., Lindblad, R., Robertson, R.P., Secchi, A., Brendel, M.D., Berney, T., Brennan, D.C., Cagliero, E., Alejandro, R., Ryan, E.A., DiMercurio, B., Morel, P., Polonsky, K.S., Reems, J.-A., Bretzel, R.G., Bertuzzi, F., Froud, T., Kandaswamy, R., Sutherland, D.E.R., Eisenbarth, G., Segal, M., Preiksaitis, J., Korbutt, G.S., Barton, F.B., Viviano, L., Seyfert-Margolis, V., Bluestone, J. and Lakey, J.R.T. (2006) International trial of the edmonton protocol for islet transplantation. The New England Journal of Medicine, 355, 1318-1330.
[14] Ferrari, G., Cusella-De, A.G., Coletta, M., et al. (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science, 279, 1528-1530. doi:10.1126/science.279.5356.1528
[15] Hakuno, D., Fukuda, K., Makino, S., et al. (2002) Bone marrow-derived regenerated cardiomyocytes (CMG Cells) express functional adrenergic and muscarinic receptors. Circulation, 105, 380-386. doi:10.1161/hc0302.102593
[16] Laflamme, M.A., Myerson, D., Saffitz, J.E. and Murry, C.E. (2000) Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts. Circulation Research, 90, 634-640. doi:10.1038/35018642
[17] Alison, M.R., Poulsom, R., Jeffery, R., Dhillon, A.P., Quaglia, A., Jacob, J., Novelli, M., Prentice, G., Williamson, J. and Wright, N.A. (2000) Hepatocytes from nonhepatic adult stem cells. Nature, 406, 257. doi:10.1038/35018642
[18] Poulsom, R., Forbes, S.J., Hodivala-Dilke, K., Ryan, E., Wyles, S., Navaratnarasah, S., Jeffery, R., Hunt, T., Alison, M., Cook, T., Pusey, C. and Wright, N.A. (2001) Bone marrow contributes to renal parenchymal turnover and regeneration. The Journal of Pathology, 195, 229-235. doi:10.1002/path.976
[19] Kopen, G.C., Prockop, D.J. and Phinney, D.G. (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proceedings of the National Academy of Sciences, 96, 10711-10716. doi:10.1073/pnas.96.19.10711
[20] Bonner-Weir, S., Taneja, M., Weir, G.C., Tatarkiewicz, K., Song, K.H., Sharma, A. and O’Neil, J.J. (2000) In vitro cultivation of human islets from expanded ductal tissue. Proceedings of the National Academy of Sciences, 97, 7999-8004. doi:10.1073/pnas.97.14.7999
[21] Ianus, A., Holz, G., Theise, N.D. and Hussain, M. (2003) In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. Journal of Clinical Investigation, 111, 843-850.
[22] Sordi, V., Malosio, M.L., Marchesi, F., Mercalli, A., Melzi, R., Giordano, T., Belmonte, N., Ferrari, G., Leone, B., Bertuzzi, F., Zerbini, G., Allavena, P., Bonifacio, E. and Piemonti, L. (2005) Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Telethon-Juvenile Diabetes Research Foundation Center for Cell Replacement, University of Milano-Bicocca, Milan.
[23] Assmus, B., Sch?chinger, V. and Teupe, C. (2002) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation, 106, 3009-3017. doi:10.1161/01.CIR.0000043246.74879.CD
[24] Strauer, B.E., Brehm, M., Zeus, T., Kostering, M., Hernández, A., Sorg, R.V., et al. (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 106, 1913-1918. doi:10.1161/01.CIR.0000034046.87607.1C
[25] Fernández-Avilés, F., San Román, J.A., García-Frade, J., Fernández, M.E., Penarrubia, M.J., De la Fuente, L., et al. (2004) Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circulation Research, 95, 742-748. doi:10.1161/01.RES.0000144798.54040.ed
[26] Wollert, K.C., Meyer, G.P., Lotz, J., Ringes-Lichtenberg, S., Lippolt, P., Breidenbach, C., et al. (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: The BOOST randomised controlled clinical trial. Lancet, 364, 141-148. doi:10.1016/S0140-6736(04)16626-9
[27] Schachinger, V., Erbs, S., Elsasser, A., Haberbosch, W., Hambrecht, R., Holschermann, H., et al. (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. The New England Journal of Medicine, 355, 1210-1221. doi:10.1056/NEJMoa060186
[28] Hahn, T., Wall, D., Camitta, B., et al. (2005) The role of cytotoxic therapy with hematopoietic stem cell transplanttation in the therapy of acute lymphoblastic leukemia in children: An evidence-based review. Biology of Blood and Marrow Transplantation, 11, 823-861. doi:10.1016/j.bbmt.2005.08.035
[29] Sanders, J.E., Im, H.J., Hoffmeister, P.A., et al. (2005) Allogeneic hematopoietic stem cell transplantation for infants with acute lymphoblastic leukemia. Blood, 105, 3749-3756. doi:10.1182/blood-2004-08-3312
[30] Centeno, C.J., Schultz, J.R., Cheever, M., Robinson, B., Freeman, M. and Marasco, W. (2010) Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Current Stem Cell Research & Therapy, 5, 81-93.
[31] Ripoll, P.L., De Prado, M. and Yelo, J. (2009) Osteonecrosis of the knee. Perfusion of iliac crest mesenchymal cells. Trauma, 20, 211-220.
[32] Pesce, M., Orlandi, A., Iachininoto, M.G., Straino, S., Torella, A.R., Rizzut, V., et al. (2003) Myoendothelial differentiation of human umbilical cord blood derived stem cells in ischemic limb tissues. Circulation Research, 93, e51-e62. doi:10.1161/01.RES.0000090624.04507.45
[33] Vicario, J.H., Campo, C.D., Gerardo, L.E., Pfeffer, H., Ortega, H.H., Agustín Yosviak, A., et al. (2008) Angiogenesis in severe peripheral arterial disease with intraarterial administration of unfractionated autologous bone marrow. Phase I. Revista de la Federacion Argentina de Cardiologia, 37, 301-309.
[34] Huang, P.P., Li, S.Z., Han, M.Z., Xiao, Z.J., Yang, R.C., Qiu, et al. (2004) Autologous transplantation of peripherals blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities. Journal of Thrombosis and Haemostasis, 91, 606-609.
[35] Huang, P., Li, S., Han, M., Xiao, Z., Yang, R. and Han, Z.C. (2005) Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blob mononuclear cell improves critical limb ischemia in diabetes. Diabetes Care, 28, 2155-2160. doi:10.2337/diacare.28.9.2155
[36] Couri, C., Oliveira, M., Stracieri, A., Moraes, D., Pieroni, F., Barros, G., Madeira, M.I., Malmegrim, K., Foss-Freitas, M., Sim?es, B., Martinez, E., Foss, M., Burt, R.K. and Voltarelli, J.C. (2009) C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA, 301, 1573-1579. doi:10.1001/jama.2009.470
[37] Gu, W.Q., Hu, J., Wang, W.Q., Li, L.R., Tang, W., Sun, S.Y., Cui, W.J., et al. (2012) Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes. Diabetes Care, 35, 1413-1419. doi:10.2337/dc11-2161
[38] Fotino, C., Ricordi, C., Lauriola, V., Alejandro R. and Pileggi, A. (2012) Bone marrow-derived stem cell transplantation for the treatment of insulin-dependent diabetes. The Review of Diabetic Studies, 7, 144-157. doi:10.1900/RDS.2010.7.144
[39] Mesples, A.D., Preti?e, B., Bellomo, R. (2007) Treatment of type 1 diabetes mellitus with pancreatic implant of autologous adult stem cell. Endocrinología y Nutrición, 54, 512-518. doi:10.1016/S1575-0922(07)71497-3
[40] Herreros, J., Chaques, J., Trainini, J., Ponton, A., Sarralde, A. and Genovese, J. (2011) Cardiac cell regeneration. Circle Cardiovascular, 18, 207-215.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.