covid
Buscar en
Endocrinología y Nutrición
Toda la web
Inicio Endocrinología y Nutrición Tratamiento de la diabetes mellitus tipo 1 con implante pancreático de células...
Información de la revista
Vol. 54. Núm. 10.
Páginas 512-518 (diciembre 2007)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 54. Núm. 10.
Páginas 512-518 (diciembre 2007)
Acceso a texto completo
Tratamiento de la diabetes mellitus tipo 1 con implante pancreático de células madre adultas autólogas
Treatment of type 1 diabetes mellitus with an autologous bone marrow adult stem cell implant in the pancreas
Visitas
5453
Alejandro Daniel Mesples
Autor para correspondencia
amesples@uolsinectis.com.ar

Correspondencia: Dr. A.D. Mesples. J.J. Urquiza 968. Salta. 4400 Argentina.
, Basilio Pretiñe, Raúl Bellomo
TECNON. Salta. Argentina
Este artículo ha recibido
Información del artículo
Resumen
Fundamento y objetivo

La diabetes mellitus tipo 1 resulta de la destrucción autoinmunitaria de las células beta del páncreas. Distintos estudios demuestran la capacidad de las células madre adultas de diferenciarse y funcionar. El objetivo fue lograr glucemias en ayunas <100mg/dl o <200mg/dl en cualquier momento del día, y supresión o disminución del 50% del aporte de insulina exógena hasta los 180 días posteriores al implante, con normalización del péptido C.

Pacientes y método

Doce pacientes con diabetes mellitus tipo 1 recibieron el implante de células madre adultas autólogas de médula ósea por cateterismo arterial desde octubre a diciembre de 2005. Se realizó a través de la arteria femoral; se cateterizó selectivamente la arteria pancreática inferior con un microcatéter y se liberó el implante en el segmento distal. Los pacientes tenían entre 21 y 60 años de edad. Los anticuerpos antiislote y/o anticuerpos antidescarboxilasa del ácido glutámico fueron negativos; el péptido C, <0,05ng/ml; la glucemia en ayunas, <180mg/dl, y la glucohemoglobina, < 9%

Resultados

El procedimiento se desarrolló sin problemas en todos los pacientes; 11 (92%) pacientes abandonaron la insulina rápida, 4 pacientes suprimieron el tratamiento con insulina, con normalización del péptido C, de la glucemia y la glucohemoglobina. Cuatro pacientes recibían menos del 66% de la dosis de insulina inicial, con aumento del péptido C; 3 pacientes recibían menos del 50% de la dosis inicial, sin cambios en el péptido C. De éstos, 2 pacientes retornaron a los requerimientos iniciales de insulina. Sólo 1 paciente no tuvo cambios significativos. A 180 días no se observaron eventos adversos.

Conclusiones

La técnica es factible y segura, y se obtuvo la recuperación funcional de la glándula a partir del implante de células madre.

Palabras clave:
Diabetes mellitus tipo 1
Cateterismo arterial periférico
Células madre adultas
Abstract
Background and objective

Type 1 diabetes results from the autoimmune destruction of β cells in the pancreas. Several studies have discussed the ability of adult stem cells to differentiate and function effectively. The aim of this study was to attain fasting glycemia of <100mg/dl, or any glycemic value of <200mg/dl at any time in the course of the day, and a decrease of at least 50% in the dose of exogenous insulin administration up to 180 days after implantation, as well as C-peptide normalization.

Patients and method

Twelve patients with type 1 diabetes mellitus were recruited for autologous bone marrow adult stem cell transplantation through an arterial catheter between October and December 2005. The catheterization was performed through the femoral artery, selectively to the inferior pancreatic artery with a microcatheter, and the implant was delivered to the distal segment. Age ranged between 21 and 60 years. Islet-cell and/or glutamic acid decarboxylase antibodies were negative, C-peptide levels were <0.05mg/ml, fasting glycemia was <180mg/dl, and glycosylated hemoglobin was < 9%.

Results

The procedure was carried out uneventfully in all patients. Eleven patients (92%) discontinued the use of rapid-acting insulin and four patients managed total suppression of insulin therapy and showed normal C-peptide, glucose, and glycosylated hemoglobin values. Four patients received less than 66% of the initial total daily insulin dose with an increase in basal C-peptide values. Three patients received less than 50% of the initial total daily dose, with no changes in basal C peptide levels. Of these, two patients resumed initial insulin requirements. Only one patient showed no significant changes after transplantation. After 180 days, no adverse events had occurred.

Conclusions

The procedure is feasible and safe and recovery of gland function was obtained after stem cell implantation.

Key words:
Type 1 diabetes mellitus
Peripheral arterial catheterization
Adult stem cells
El Texto completo está disponible en PDF
Bibliografía
[1]
The Diabetes Control and Complications Trial Research Group.
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
N Engl J Med, 329 (1993), pp. 977-986
[2]
D.E. Undlien, E. Thorsby.
HLA associations in type 1 diabetes: merging genetics and immunology.
Trends Immunol, 22 (2001), pp. 467-469
[3]
D. Mathis, L. Vence, C. Benoist.
Beta-cell death during progression to diabetes.
Nature, 414 (2001), pp. 792-798
[4]
A.C. Gruessner, D.E. Sutherland.
Analysis of United States (US) and non-US pancreas transplants reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of October 2001.
Clinical transplants 2001, pp. 41-72
[5]
D.W. Scharp, P.E. Lacy, J.V. Santiago, C.S. McCullough, L.G. Weide, L. Falqui, et al.
Insulin independence after islet transplantation into type I diabetic patient.
Diabetes, 39 (1990), pp. 515-518
[6]
J. Shapiro.
Eighty years after insulin: parallels with modern islet transplantation.
CMAJ, 167 (2002), pp. 1398-1400
[7]
J.H. Nielsen, T. Mandrup-Poulsen, J. Nerup.
Direct effects of cyclosporin A on human pancreatic beta-cells.
Diabetes, 35 (1986), pp. 1049-1052
[8]
M.C. Fabian, J.R. Lakey, R.V. Rajotte, N.M. Kneteman.
The efficacy and toxicity of rapamycin in murine islet transplantation: in vitro and in vivo studies.
Transplantation, 56 (1993), pp. 1137-1142
[9]
J.B. Redmon, L.K. Olson, M.B. Armstrong, M.J. Greene, R.P. Robertson.
Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HITT15 cells.
J Clin Invest, 98 (1996), pp. 2786-2793
[10]
D. De la Tour, T. Halvorsen, C. Demeterco, B. Tyrberg, P. Itkin-Ansari, M. Loy, et al.
Beta-cell differentiation from a human pancreatic cell line in vitro and in vivo.
Mol Endocrinol, 15 (2001), pp. 476-483
[11]
N. Lumelsky, O. Blondel, P. Laeng, I. Velasco, R. Ravin, R. McKay.
Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets.
Science, 292 (2001), pp. 1389-1394
[12]
S. Assady, G. Maor, M. Amit, J. Itskovitz-Elder, K.L. Skorecki, M. Tzukerman.
Insulin production by human embryonic stem cells.
Diabetes, 50 (2001), pp. 1691-1697
[13]
G. Berna, T. Leon-Quinto, R. Ensenat-Waser, E. Montanya, F. Martin, B. Soria.
Stem cells and diabetes.
Biomed Pharmacother, 55 (2001), pp. 206-212
[14]
H. Edlund.
Factors controlling pancreatic cell differentiation and function.
Diabetologia, 44 (2001), pp. 1071-1079
[15]
B. Soria.
In-vitro differentiation of pancreatic beta-cells.
Differentiation, 68 (2001), pp. 205-219
[16]
D.R. Sutherland, L. Anderson, M. Keeney, R. Nayar, I. Chin Yee.
The ISHAGE Guidelines for CD34+ cells determination by flow cytometry.
J Hematother, 5 (1996), pp. 213-226
[17]
ADA. Expert Committee on the diagnosis and classification of Diabetes Mellitus.
Report of the Experts.
Diabetes Care, 20 (1997), pp. 1183-1197
[18]
S. Fuchs, L.F. Satler, R. Kornowski, P. Okubagzi, G. Weisz, R. Baffour, et al.
Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease.
Am J Cardiol, 41 (2003), pp. 1721-1724
[19]
B. Assmus, V. Schächinger, C. Teupe.
Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI).
Circulation, 106 (2002), pp. 3009-3017
[20]
J.H. Vicario, C. Campos, J.R. Piva, F. Faccio.
Médula ósea autóloga vía seno coronario y angiogénesis en pacientes con angina crónica estable. Fase I.
Rev Fed Arg Cardiol, 33 (2004), pp. 357-363
[21]
Q.L. Ying, J. Nichols, E.P. Evans, A.G. Smith.
Changing potency by spontaneous fusion.
Nature, 416 (2002), pp. 545-548
[22]
D. Hess, L. Li, M. Martin, S. Sakano, D. Hill, B. Strutt, et al.
Bone marrow –derived stem cells initiate pancreatic regeneration.
Nature Biotechnology, 21 (2003), pp. 763-770
[23]
A. Ianus, G.G. Holz, N.D. Theise, M.A. Hussain.
In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion.
J Clin Invest, 111 (2003), pp. 843-850
[24]
M.R. Alison.
Hepatocyte from non-hepatic adult stem cells.
Nature, 406 (2000), pp. 257-260
[25]
B.E. Petersen.
Bone marrow as a potential source of hepatic oval cells.
Science, 284 (1999), pp. 1168-1170
[26]
A.M.J. Shapiro, J.R.T. Lakey, E.A. Ryan, G.S. Korbutt, E. Toth, G.l. Warnock, et al.
Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.
N Engl J Med, 343 (2000), pp. 230-238
[27]
B. Soria, E. Roche, G. Berna, T. Leon-Quinto, J.A. Reig, F. Martin.
Insulin-secreting cells derived from embryonic stem cells normalize glycaemia in streptozotocin-induced diabetic mice.
Diabetes, 49 (2000), pp. 157-162
[28]
B. Soria, A. Skoudy, F. Martín.
From stem cells to beta cells: new strategies in cell therpy of diabetes mellitus.
Diabetologia, 44 (2001), pp. 407-415
[29]
J. Taneera, A. Rosengren, E. Renstrom, J.M. Nygren, P. Serup, P. Rorsman, et al.
Failure of transplanted bone marrow cells to adopt a pancreatic β-cell fate.
Diabetes, 55 (2006), pp. 290-296
Copyright © 2007. Sociedad Española de Endocrinología y Nutrición
Opciones de artículo
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos