Stem Cell Research & Therapy | Full text | A preliminary …

Abstract Introduction

Stem cell therapy has recently been introduced to treat patients with type 2 diabetes mellitus (T2DM). However, no data are available on the efficacy and safety of allogeneic Whartons Jelly-derived mesenchymal stem cell (WJ-MSC) transplantation in patients with T2DM. Here we performed a non-placebo controlled prospective phase I/II study to determine efficacy and safety of WJ-MSC transplantation in T2DM.

Twenty-two patients with T2DM were enrolled and received WJ-MSC transplantation through one intravenous injection and one intrapancreatic endovascular injection (catheterization). They were followed up for 12months after transplantation. The primary endpoints were changes in the levels of glycated hemoglobin and C-peptide and the secondary endpoints included insulin dosage, fasting blood glucose (FBG), post-meal blood glucose (PBG), inflammatory markers and T lymphocyte counts.

WJ-MSC transplantation significantly decreased the levels of glucose and glycated hemoglobin, improved C-peptide levels and beta cell function, and reduced markers of systemic inflammation and T lymphocyte counts. No major WJ-MSC transplantation-related adverse events occurred, but data suggest a temporary decrease in levels of C-peptide and beta cell function at one month after treatment, possibly related to intrapancreatic endovascular injection.

Our data demonstrate that treatment with WJ-MSCs can improve metabolic control and beta cell function in patients with T2DM. The therapeutic mechanism may involve improvements in systemic inflammation and/or immunological regulation.

Chinese Clinical Trial Register ChiCTR-ONC-10000985. Registered 23 September 2010

Type 2 diabetes mellitus (T2DM) is a metabolic stress resulting from over-nutrition- and insufficient activity-induced insulin resistance and -cell impairment [1,2]. The continuing hyperglycemia results in both microvascular and macrovascular complications. It is important for patients to maintain nearly normal glycemic levels to reduce their risk of diabetic complications.

Although diet control, physical exercise and oral anti-diabetic drugs are all effective in decreasing hyperglycemia, it is difficult for many patients to achieve good glycemic control depending only on these options, and most of these patients will eventually require insulin therapy [3]. However, insulin treatment negatively impacts patients daily lives and is frequently associated with hypoglycemic episodes. Therefore, it is imperative to explore new strategies for optimal glycemic control or -cell replacement.

In recent years, several animal studies and clinical trials have shown that mesenchymal stem cell (MSC) transplantation can improve glycemic control and beta cell function [4,5]. XY Li and colleagues designed a clinical study to treat foot disease in patients with type 2 diabetes mellitus using human umbilical cord blood mesenchymal stem cells (hUCB-MSC) and indicated that levels of blood glucose and required insulin dosage were reduced after hUCB-MSC transplantation accompanied by improved clinical profiles in diabetic patients [6]. However, the exact mechanisms of reversing hyperglycemia remain unknown. A chronic inflammatory process has been demonstrated in insulin-sensitive tissues and pancreatic islets, which results in insulin resistance and beta-cell destruction [7,8]. MSCs have demonstrated anti-inflammatory roles in the treatment of many diseases, such as myocardial infarction [9], lung injury [10] and systemic lupus erythematosus [11]. In addition, MSCs play a role in immunoregulation in the therapy of graft-versus-host disease [12] and autoimmune disorders [13]. Therefore, we hypothesized that Whartons Jelly mesenchymal stem cell (WJ-MSC) transplantation could be a therapeutic option in T2DM, and the mechanism may involve improvements in inflammation and immunoregulation.

On the basis of these observations, we initiated a prospective phase I/II study using WJ-MSCs in patients with T2DM. In this report, we explored the efficacy and safety of WJ-MSC transplantation in T2DM patients and followed up with them for 12months after treatment.

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Stem Cell Research & Therapy | Full text | A preliminary ...