Mesenchymal stem cell-based therapy for type 1 & 2 diabetes mellitus patients: a systematic review and meta-analysis of randomized controlled trials

Abstract

Objective: To systematically and statistically evaluate evidence from randomized controlled trials (RCTs) investigating the efficacy and safety of somatic stem cells in achieving glycemic control in type 1 and 2 diabetic patients.

Methods: Bibliographic databases including PubMed, Scopus, Web of Science, and Cochrane Library were searched from the time of their establishment till January 2024. Obtained records were meticulously screened by title, abstract, and full text to include only RCTs seeking mesenchymal stem cells (MSCs) treatment for type 1 diabetes mellitus (T1DM) and 2 diabetes mellitus (T2DM). Included studies underwent quality assessment using the Cochrane risk of bias 2 tool (ROB2).

Results: Thirteen studies were deemed eligible for meta-analysis, encompassing 507 patients (T1DM = 199, T2DM = 308). To measure treatment efficacy, the present meta-analysis was conducted on outcomes reported after 12 months following treatment. MSCs therapy group was associated with a significantly reduced glycosylated hemoglobin (HbA1c) compared to the control group, MD = -0.72; 95% CI: [-1.11 to -0.33], P = 0.0003, I² = 56%. Daily insulin requirement was lower in the MSCs group versus placebo, MD = -14.50; 95% CI: [-19.45 to -9.55], P < 0.00001, I² = 0%. Pooled fasting C-peptide levels were significantly higher in the MSCs group compared to placebo, MD = 0.24; 95% CI: [0.05 to 0.43], P = 0.01, I² = 93%. Postprandial blood glucose (PPBG) was observed to be significantly lower in the MSCs arm in contrast to placebo, MD = -11.32; 95% CI: [-16.46 to -6.17], P < 0.0001, I² = 17%. However, pooled analysis of fasting blood glucose (FBG) was not significantly different between both groups, MD = -6.22; 95% CI: [-24.23 to 11.79], P = 0.50, I² = 81% at the end of the 12-month follow-up.

Conclusion: Mesenchymal stem cell-derived therapy is an efficacious glycemia-lowering modality agent compared to conventional therapy in T1DM and T2DM patients. Albeit more sizeable and longer RCTs are warranted to further support and standardize their clinical use.

Keywords: Diabetes mellitus; Glycated hemoglobin; Glycemic control; Hematopoietic stem cells; Mesenchymal stem cells; Stem cells; Type 1 diabetes mellitus; Type 2 diabetes mellitus; Umbilical cord stem cells.

Fig. 1

PRISMA flowchart diagram of the literature screening & inclusion process

Fig. 2

Quality assessment of included literature. (a) Traffic light map of included studies risk of bias according to each bias domain. (b) Combined quality of assessment of included studies for reach bias domain

Fig. 3

Forest plot showing the results at 3-month follow-up for both types of DM: (A) Comparison of the HbA1c, (B) Comparison of the FBG, (C) Comparison of the PPBG

Fig. 4

Forest plot showing the results at 3-month follow-up for both types of DM: (A) Comparison of the fasting C-peptide levels, (B) Comparison of the Insulin requirement

Fig. 5

Forest plot showing the results at 6-month follow-up for both types of DM: (A) Comparison of the HbA1c, (B) Comparison of the FBG, (C) Comparison of the PPBG

Fig. 6

Forest plot showing the results at 6-month follow-up for both types of DM: (A) Comparison of the fasting C-peptide levels, (B) Comparison of the Insulin requirement, (C) Comparison of the stimulated C-peptide levels

Fig. 7

Forest plot showing the results at 12-month follow-up for both types of DM: (A) Comparison of the HbA1c, (B) Comparison of the FBG

Fig. 8

Forest plot showing the results at 12-month follow-up for both types of DM: (A) Comparison of the PPBG, (B) Sensitivity analysis of the PPBG, (C) Comparison of the fasting C-peptide levels

Fig. 9

Forest plot showing the results at 12-month follow-up for both types of DM: (A) Comparison of the insulin requirement, (B) Sensitivity analysis of the insulin requirement, (C) Comparison of the stimulating C-peptide levels

Fig. 10

Funnel plot for potential publication bias analysis. The potential publication bias of the effects of MSC therapy on (A) HbA1c and (B) fasting c-peptide