Stem cell therapy for endocrine and metabolic disorders

Table 2 The clinical trials using stem cells in the treatment of type 2 diabetes

Ref.	Year	Type of SCs	No.	HbA1c	TIR	Fasting C-peptide	Postprandial C-peptide	Diabetic medication dose	Other indicators
[33]	2017	Autologous BM-MSCs	10	6/10 patients reduced below 7%, but no significant improvement relative to baseline		No significant improvement relative to baseline	No significant improvement relative to baseline	6/10 patients achieved a > 50% reduction in insulin dose relative to baseline	ISI: Had a significant improvement (0.1 to 0.4 μmol/kg/minute/pmol/L)a
[34]	2021	Autologous BM-MSCs	30	Patients with duration of < 10 years and a BMI of < 23 kg/m2 showed a reduction of 0.7 percentage points (from 8.9% ± 1.6% to 8.2% ± 0.5%)a; no significant change (even increase) in patients with duration of > 10 years		Patients with duration of < 10 years and a BMI of < 23 kg/m2 showed a slight decreasec, whereas those with duration of > 10 years showed a significant declinea		2/4 patients using only insulin had an average reduction of 6 IU/day; 5/10 patients using multiple drugs had an average reduction of 868 mg/day; 1/3 patients using insulin and a single drug had a decrease in drug dose but an increase in insulin dose; 8/11 patients using insulin and multiple drugs: 5 of these 8 patients showed reduced use of oral drugs, and 2 patients had a decreased insulin dose
[35]	2011	Allogeneic PD-MSCs	10	Decreased by 3.1 percentage points (9.8% to 6.7%)a		Increased by 34.62% (2.6 ± 2.1 ng/mL to 3.5 ± 2.3 ng/mL)a	Increased by 31.71% (5.6 ± 4.0 ng/mL to 8.2 ± 3.9 ng/mL)a	Decreased by 45.53% (63.7 ± 18.7 to 34.7 ± 13.4 IU)a; insulin dose was reduced for 4/10 patients by > 50%
[36]	2014	Allogeneic WJ-MSCs	22	Decreased by 1.2 percentage points (8.20% ± 1.69% to 7.0% ± 0.60%)a		Increased to the peak value at month 6 (1.95 ± 1.3 ng/mL, increased by 51.16%)a, followed by slight decrease at month 12 (1.86 ± 1.0 ng/mL, which still represents 44.19%a increase relative to baseline (1.29 ± 0.83 ng/mL)	No significant difference compared to baseline	(1) 16/17 patients using insulin had a dose reduction of 53.06% (0.49 ± 0.22 to 0.23 ± 0.19 IU/kg/day)a, 7 patients achieved insulin independence, which was maintained until the last follow-up; 5 patients had a dose reduction of ≥ 50%; and (2) 1/5 patients using drugs became completely drug-free, which was maintained until the last follow-up, 4/5 had a dose reduction of > 50	HOMA-2B: Increased by 49.81%a at month 6 (98.86% ± 43.91%) and 30.32%a at month 12 (86.0% ± 37.1%) (65.99% ± 23.49% at baseline)
[37]	2022	Allogeneic UC-MSCs	45	Decreased 1.5 percentage points (9.02% ± 1.27% to 7.52% ± 1.07%)a in the UC-MSC group, and 0.7 percentage points in the control group (8.89% ± 1.11% to 8.19% ± 1.02%)c; with a significant difference noted between the two groupsa		No significant increase compared with the baseline (2.01 ± 0.70 to 2.07 ± 0.70 ng/mL)c; no significant difference between the two groups either	No significant change compared with the baseline (1.94 ± 0.61 to 1.92 ± 0.53 ng/mL)c; no significant difference between the two groups either	The percentage of insulin reduction was significantly higher in the UC-MSC group than in the control group (27.78% vs 15.62%)a	GIR: Increased by 52.56% in the UC-MSC group (3.12 to 4.76 mg/minute/kg)a, but no significant change was noted in the control group (3.26 to 3.60 mg/minute/kg)c; a significant difference was noted between the two groupsa
[38]	2024	hiPSCs	1	Decreased by 2.0 percentage points (6.6% to 4.6%)	(Target range: 3.9-10 mmol/L) increased by 12.3 percentage points (87.7% to 100%)	Increased to a peak of 1.09 nmol/L at week 24 (increased by 374%, 0.23 nmol/L at baseline) and then decreased but remained within the normal range	AUC·180 minutes of C-peptide: Increased by 49.64% (246.8 to 369.3 nmol/L)	Insulin and oral medications were discontinued at week 11 and 56, respectively, and were maintained until the last follow-up	TITR (target range: 3.9-7.8 mmol/L): Increased by 43.3 percentage points (56.7% to 100%)

^aP < 0.05.

^cP > 0.05.

No.: Number of stem cell-treated patients; SCs: Stem cells; TIR: Time in range; BM-MSCs: Bone marrow-derived mesenchymal stem cells; ISI: Insulin sensitivity index; BMI: Body mass index; PD-MSCs: Placenta-derived mesenchymal stem cells; WJ-MSCs: Wharton’s jelly-derived mesenchymal stem cells; UC-MSCs: Umbilical cord-derived mesenchymal stem cells; GIR: Glucose infusion rate; hiPSCs: Human induced pluripotent stem cells; AUC: Area under the curve; TITR: Time in tight range.