Abstract

BackgroundStem cell therapy provides great hope for patients with diabetes mellitus (DM). DM is a seriously alarming metabolic disease characterized by hyperglycemia and β cell dysfunction. Efficient novel therapeutic modalities to treat DM are indeed warranted. Stem cells (SC) derived from the umbilical cord specifically provide several advantages and unique characteristics being a readily available non-invasive source, with an additional credit for their banking potential. This meta-analysis study aims to provide a focused assessment for therapeutic efficacy of umbilical cord (UC)-derived SC-transplantation, namely Wharton’s jelly mesenchymal stem cells (WJ-MSCs) and umbilical cord blood (UCB) for DM.MethodsThe clinical efficacy was evaluated based on glycemic control status (reflected on HbA1c%) and β cell function (reflected on C-peptide levels), as well as the daily insulin requirement in diabetic patients after receiving UC-derived SC-transplantation compared to baseline values. Moreover, we assessed these outcome measures in patients who received such intervention compared to those who did not receive it in randomized/non-randomized controlled clinical trials. We employed a random-effects model and standardized mean difference for this meta-analysis.ResultsEleven eligible clinical studies were included; WJ-MSCs (6 studies; 172 patients including 71 controls) and UCB (5 studies; 74 patients including 15 controls). WJ-MSCs significantly improved HbA1c% (pooled-estimate − 1.085; 95%CI (− 1.513, − 0.657); p < 0.001) and C-peptide levels (pooled-estimate 1.008; 95%CI (0.475, 1.541); p < 0.001), as well as the daily insulin-requirement (pooled-estimate − 2.027; 95%CI (− 3.32, − 0.733); p = 0.002). On the contrary, UCB was found to be uniformly ineffective; HbA1c% (pooled-estimate − 0.091, 95%CI (− 0.454, 0.271); p = 0.622), significantly deteriorated C-peptide levels (pooled-estimate − 0.789; 95%CI (− 1.252, − 0.325); p < 0.001) and daily insulin-requirement (pooled-estimate 0.916; 95%CI (0.247, 1.585); p = 0.007). All these observations remained consistent when we carried out sub-group meta-analysis for T1DM and T2DM and also when we compared patients who received WJ-MSCs or UCB to controls.ConclusionsThe results of our meta-analysis provide a clear evidence for the superior efficacy of WJ-MSCs over UCB in DM. This sheds lights on the importance to consider banking of WJ-MSCs together with the well-established routine UCB-banking, especially for those with family history of DM. Additionally, further clinical studies are required to investigate therapeutic efficacy of selected/enriched UCB-derived cell populations with immunomodulatory/regenerative potential in DM.

Highlights

  • Stem cell therapy provides great hope for patients with diabetes mellitus (DM)

  • The results of our meta-analysis provide a clear evidence for the superior efficacy of Wharton’s jelly (WJ)-mesenchymal stem cells (MSCs) over umbilical cord blood (UCB) in DM

  • 8 citations were further excluded for the following reasons; 4 studies for being a stem-cell educator study in which stem cell transplantation was not applied as an intervention [16,17,18, 25], 1 study for having an additional pathology to DM [31], and 3 studies were excluded due to lack of data [32,33,34]

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Summary

Introduction

Stem cell therapy provides great hope for patients with diabetes mellitus (DM). DM is a seriously alarming metabolic disease characterized by hyperglycemia and β cell dysfunction. Stem cells (SC) derived from the umbilical cord provide several advantages and unique characteristics being a readily available non-invasive source, with an additional credit for their banking potential. Diabetes mellitus (DM) is a terribly growing epidemic, currently affecting about 463 million people worldwide, with expected rise to 700 million by the year 2045 [1]. It is the most prevalent metabolic disease, in which insulin secreting β cells are damaged to various extents. Regenerative medicine and stem cell therapy opened new avenues and ignited much hope for patients with DM over the past few years [7]

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