A preliminary evaluation of efficacy and safety of Wharton's jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus

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 Wharton's 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.

Methods: 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 12 months 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.

Results: 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.

Conclusions: 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.

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

Figure 1

Fluorescence-activated cell sorting analysis of umbilical cord mesenchymal stem cells. Percentages of all CD105, CD73 and CD44 were higher than 95%, while none of CD34, CD45, CD31, CD146 and HLA-DR’s percentage was higher than 1%. WJ-MSCs, Wharton’s Jelly mesenchymal stem cells.

Figure 2

Changes in glycated hemoglobin, fasting glucose and 2 h postprandial glucose levels during the 12-month study period. A: The changes in glycated hemoglobin levels between baseline and 1, 3, 6 and 12 months. B: Changes in fasting glucose and 2 h postprandial glucose levels between baseline and 1, 3, 6 and 12 months. The results are shown as the mean ± S.D. *P <0.05 compared with pretreatment; **P <0.01 compared with pretreatment.

Figure 3

Changes in C-peptide levels and beta-cell secretory function during the 12-month study period. A: The changes in fasting C-peptide levels and OGTT 2 h postprandial C-peptide levels between baseline and 1, 3, 6 and 12 months. B: Beta-cell secretory function was assessed with HOMA-2B. The results are shown as the mean ± S.D. *P <0.05 compared with pretreatment. HOMA, homeostasis model assessment; OGTT, oral glucose tolerance test.

Figure 4

Changes in daily insulin requirements over time. This figure shows the insulin requirements of T2DM patients at pre-operation and 1, 3, 6 and 12 months post-transplantation. The results are shown as the mean ± S.D. *P <0.05 compared with pretreatment. The analysis included 17 patients that received exogenous insulin at months 0, 1, 3, 6 and 12. T2DM, Type 2 diabetes mellitus.

Figure 5

The immunologic tests and markers of systemic inflammation. A: The changes in the numbers of CD3⁺, CD4⁺ and CD8⁺ T lymphocytes between baseline and six months. B: Changes in the serum levels of IL-6, IL-10, IL-1β and TNF-α between baseline and six months. The results are shown as the mean ± S.D. *P <0.05 compared with pretreatment. The analysis included 22 patients before and six months after umbilical cord mesenchymal stem cell transplantation.