Therapeutic potential of stem cells from human exfoliated deciduous teeth infusion into patients with type 2 diabetes depends on basal lipid levels and islet function

Abstract

Mesenchymal stem cells (MSCs) hold great potential in treating patients with diabetes, but the therapeutic effects are not always achieved. Particularly, the clinical factors regulating MSC therapy in this setting are largely unknown. In this study, 24 patients with type 2 diabetes mellitus (T2DM) treated with insulin were selected to receive three intravenous infusions of stem cells from human exfoliated deciduous teeth (SHED) over the course of 6 weeks and were followed up for 12 months. We observed a significant reduction of glycosylated serum albumin level (P < .05) and glycosylated hemoglobin level (P < .05) after SHED transplantation. The total effective rate was 86.36% and 68.18%, respectively, at the end of treatment and follow-up periods. Three patients ceased insulin injections after SHED transplantation. A steamed bread meal test showed that the serum levels of postprandial C-peptide at 2 hours were significantly higher than those at the baseline (P < .05). Further analysis showed that patients with a high level of blood cholesterol and a low baseline level of C-peptide had poor response to SHED transplantation. Some patients experienced a transient fever (11.11%), fatigue (4.17%), or rash (1.39%) after SHED transplantation, which were easily resolved. In summary, SHED infusion is a safe and effective therapy to improve glucose metabolism and islet function in patients with T2DM. Blood lipid levels and baseline islet function may serve as key factors contributing to the therapeutic outcome of MSC transplantation in patients with T2DM.

Keywords: diabetes; glucose metabolism; islet function; mesenchymal stem cells; stem cells from human exfoliated deciduous teeth.

FIGURE 1

Changes of the glucose metabolism indexes during the study period. A, Patients' GSP levels from baseline to 1 month after the end of treatment period. *P < .05 vs the baseline level. B, Changes of the HbA1c levels during the study period. *P < .05 vs the baseline level. C,D, Patients' FBG levels (C) and self‐monitored fasting CBG values (D) during the study period. CBG, capillary blood glucose; FBG, fasting blood glucose; GSP, glycosylated serum albumin; HbA1c, glycosylated hemoglobin

FIGURE 2

Changes of the glucose metabolism and islet function in the steamed bread meal test. A, Patients' FBG, P1hBG, and P2hBG levels at the baseline, the end of the treatment period and 3, 6, 9, and 12 months after the third infusion of stem cells from human exfoliated deciduous teeth. B, Changes of the FCP, F1hCP, and F2hCP levels during the study period. *P < .05 vs the baseline level. C, Changes of patients' HOMA‐IR during the study period. FBG, fasting blood glucose; FCP, fasting C‐peptide; HOMA‐IR, insulin resistance index; P1hBG, 1‐hour postprandial blood glucose; P1hCP, 1‐hour postprandial C‐peptide; P2hBG, 2‐hour postprandial blood glucose; P2hCP; 2‐hour postprandial C‐peptide

FIGURE 3

Changes of blood lipids in patients during the study period. Patients' TC, A, TG, B, HDL‐C, C, and LDL‐C levels, D, during the study period. *P < .05 vs the baseline level. HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides

FIGURE 4

Analysis of the therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) transplantation therapy. A, Changes of daily insulin dose in 24 patients during the study period. B, Analysis of the efficiency of SHED transplantation therapy in 22 patients

FIGURE 5

Correlation analysis on the effects of transplantation therapy with stem cells from human exfoliated deciduous teeth. A, HbA1c level before stem cell transplantation affected daily insulin dose at the end of the study. B,C, Baseline FCP (B) and P2hCP (C) levels affected the FCP level at the end of the study. D‐F, Patients' TC (D), TG (E), and LDL‐C (F) levels before treatment affected the daily insulin dose at the end of the study. FCP, fasting C‐peptide; HbA1c, glycosylated hemoglobin; IN, insulin; LDL‐C, low‐density lipoprotein cholesterol; P2hCP, 2‐hour postprandial C‐peptide; TC, total cholesterol; TG, triglycerides

FIGURE 6

Incidence of hypoglycemia during the study period. A, Hypoglycemia episodes in all patients. B, Frequency of hypoglycemia in each patient