A meta-analysis on application and prospect of cell therapy in the treatment of diabetes mellitus

Abstract

Objective: Diabetes mellitus (DM) is a grave autoimmune disorder because of no insulin self-generation. Currently, mainly clinical methods exist, serious adverse effects leading to stem cell therapy are considered. The mesenchymal stem cells (MSCs), require high differentiation capacity and are judged as crucial in DM treatment. The meta-analysis aimed to systemically analyze the particular types of MSCs which play a more important role in DM and which DM is treated more effectively.

Method: A systematic review was conducted on the published literature, clinical trials and observational studies, utilizing databases such as PubMed, Embase, Cochrane and clinicaltrial.gov. RevMan software was adopted to draw Forest Plot and Funnel Plot, and subgroup analysis were employed to evaluate heterogeneity between different groups.

Results: We identified the meta-analyses of 34 unique random controlled trials and divided our own systematic reviews into 8 groups. The MSCs were associated with placebo (OR = 2.79, 95% CI [1.63, 4.75]), Standard Clinical Treatment (SCT) (OR = 4.12, 95% CI [2.76, 6.14]), and monocyte (OR = 6.52, 95% CI [3.56, 9.48]). The comparison between Autologous MSCs and Allogenic MSCs (OR = 4.64, 95% CI [3.42, 6.31]), Autologous BMMSCs and other MSCs (OR = 5.28, 95% CI [3.64, 7.66]), Allogenic ASCs and UCMSCs (OR = 3.54, 95% CI [1.83, 6.86]), Type I DM and Type II DM (OR = 3.10, 95% CI [1.79, 5.38]), intravenous injection and other injections (OR = 4.81, 95% CI [3.34, 6.94]), diabetic foot ulcers and diabetic neurological disease (OR = 3.88,,95% CI [2.53,5.95]).

Conclusion: Current evidence suggests that MSCs hold significant potential for treating DM, demonstrating considerably high safety and efficacy. MSCs exhibit higher therapeutic benefits compared to monocytes, with autologous MSCs offering better clinical outcomes than allogenic sources. MSCs (BMMSCs) proved more effective than other types of MSCs. However, no significant differences were observed between adipose-derived MSCs (ASCs) and umbilical cord-derived MSCs (UCMSCs) in the allogeneic setting. Moreover, MSCs show more pronounced therapeutic effects in Type II DM, and the difference among the injection methods is minimally observed. In conclusion, the research scope on DM is relatively limited in this study and further research is necessary to improve the reliability of the estimates.

Keywords: Allogenic MSCs; Autologous MSCs; Exosomes; MSCs; Type I DM; Type II DM; iPSC.

Fig. 1

Flow diagram of the meta-analysis study selection process

Fig. 2

The graph of risk assessment. risk of bias graph about the meta-analysis of DM mellitus treated with MSCs. B) Risk of bias summary about the meta-analysis of DM mellitus treated with MSCs

Fig. 3

(a) stands for Forest plot. The forest plots of the included studies compare MSCs versus placebo/no treatment control for treating DM mellitus. (b)stand for the Funnel plot. The funnel plot of the included studies comparing MSCs versus placebo/no treatment control for treating DM mellitus

Fig. 4

(a) stands for Forest plot. The forest plots of the included studies compare MSCs (MSC) versus standard clinical treatments SCT for treating DM mellitus. (b) stand for the Funnel plot. The funnel plot of the included studies comparing MSCs (MSC) versus standard clinical treatments SCT for treating DM mellitus

Fig. 5

(a) Forest plots. The forest plots of the included studies comparing MSCs (MSC) versus monocytes for treating DM mellitus. (b) Funnel plot. The funnel plot of the included studies comparing MSCs (MSC) versus monocytes for treating DM mellitus

Fig. 6

(a) stands for Forest plot. The forest plots of the included studies compare Autologous versus Allogeneic for treating DM mellitus. (b) stand for the Funnel plot. The funnel plot of the included studies comparing autologous versus allogeneic for treating DM mellitus

Fig. 7

(a) stands for Forest plot. The forest plots of the included studies comparing BMMSCs and the other MSCs for treating DM mellitus. (b) stand for the Funnel plot. The funnel plot of the included studies comparing BMMSCs and the other MSCs for treating DM mellitus

Fig. 8

(a) stands for Forest plot. The forest plots of the included studies comparing ASCs and UCMSCs for treating DM mellitus. (b) stand for the Funnel plot. The funnel plot of the included studies comparing AMSCs and UCMSCs for treating DM mellitus

Fig. 9

(a) stands for Forest plot. The forest plots of them included studies comparing Type I and Type II for treating DM mellitus. (b) stand for the Funnel plot. The funnel plot of the included studies comparing Type I and Type II for treating DM mellitus

Fig. 10

(a) stand for Forest plot. The forest plots of the included studies compare intravenous injections and other injections for treating DM mellitus. (b) stand for the Funnel plot. The funnel plot of the included studies comparing intravenous injection and other injections for treating DM mellitus

Fig. 11

(a) stand for Forest plot. The forest plots of the included studies compare diabetic foot ulcer and diabetic neurological disease for treating DM mellitus. (b) stand for the Funnel plot. The funnel plot of the included studies comparing diabetic foot ulcer and diabetic neurological disease for treating DM mellitus