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Bone marrow-derived stem cell transplantation for the treatment of insulin-dependent diabetes.

ABSTRACT: The bone marrow is an invaluable source of adult pluripotent stem cells, as it gives rise to hematopoietic stem cells, endothelial progenitor cells, and mesenchymal cells, amongst others. The use of bone marrow-derived stem cell (BMC) transplantation (BMT) may be of assistance in achieving tissue repair and regeneration, as well as in modulating immune responses in the context of autoimmunity and transplantation. Ongoing clinical trials are evaluating the effects of BMC to preserve functional beta-cell mass in subjects with type 1 and type 2 diabetes, and to favor engraftment and survival of transplanted islets. Additional trials are evaluating the impact of BMT (i.e., mesenchymal stem cells) on the progression of diabetes complications. This article reviews the progress in the field of BMC for the treatment of subjects with insulin-dependent diabetes, and summarizes clinical data of pilot studies performed over the last two decades at our research center by combining allogeneic islet transplantation with donor-specific BMC. Clinical data is summarized from pilot studies performed at our research center over the last two decades.

SUBMITTER: Fotino C

PROVIDER: S-EPMC2989787 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Bone marrow-derived stem cell transplantation for the treatment of insulin-dependent diabetes.

Fotino Carmen C Ricordi Camillo C Lauriola Vincenzo V Alejandro Rodolfo R Pileggi Antonello A

The review of diabetic studies : RDS 20100810 2

The bone marrow is an invaluable source of adult pluripotent stem cells, as it gives rise to hematopoietic stem cells, endothelial progenitor cells, and mesenchymal cells, amongst others. The use of bone marrow-derived stem cell (BMC) transplantation (BMT) may be of assistance in achieving tissue repair and regeneration, as well as in modulating immune responses in the context of autoimmunity and transplantation. Ongoing clinical trials are evaluating the effects of BMC to preserve functional be ...[more]

PMID: 21060973

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Project description:BACKGROUND:Insulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the ?-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target ?-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies. METHODS:Seven T2DM patients with the duration of disease ?5 years, receiving triple oral anti-diabetic drugs along with insulin (?0.4 IU per kg per day) and HbA1c ? 7.5% (?58.0 mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by ?50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation. RESULTS:Six out of 7 (90%) patients achieved the primary end-point. At 6 months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p < 0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p = 0.018), whereas there were no significant alterations in insulin sensitivity and glucose disposal rate during hyperinsulinemic-euglycemic clamp relative to the baseline. Other measures of ?-cell indices like HOMA-?, and stimulated C-peptide response to glucagon and mixed meal tolerance test were non-contributory. CONCLUSION:ABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict ?-cell function in patients with advanced duration of T2DM. Trial registration-Clinicaltrials.gov NCT01759823.

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Bone marrow-derived stem cell transplantation for the treatment of insulin-dependent diabetes.

Publications

Bone marrow-derived stem cell transplantation for the treatment of insulin-dependent diabetes.

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