Stem cell therapy for endocrine and metabolic disorders

Table 1 The clinical trials using stem cells in the treatment of type 1 diabetes

Ref.	Year	Type of SCs	No.	HbA1c	TIR	Fasting C-peptide	Postprandial C-peptide	Insulin dose
[15]	2021	hESCs	15	< 7% over all follow-up	Increasedb	Increaseda	Both glucose and meal-responsive C-peptide increaseda	Decreasedb (1/15 patients decreased of 50%)
[16]	2025	hiPSCs	14	< 7% after 120 days, decreased by 1.81 percentage points at 1 year (7.8% at baseline)	> 70% at day 150, increased by 44.4 percentage points at day 365 (49.5% to 93.9%)	Detected at day 90 (undetectable at baseline)	With an average value of 424 pmol/L at day 90 and 1274 pmol/L at day 365 (undetectable at baseline)	The average insulin dose decreased by 92%; 10/12 patients achieved insulin independence and did not resume through day 365; insulin dose was decreased for 2/12 patients
[17]	2024	hiPSCs	1	Decreased by 1.07 percentage points at day 75 (7.57% to 6.50%) and then remained within the non-diabetic range (< 5.7%)	Increased by 55.41 percentage points (43.18% to 98.59%)	Increased to 102.6 pmol/L after 1 week; increased to a plateau after achieving insulin independence, with a fluctuation range of 407.1 to 721.6 pmol/L (undetectable at baseline)	Increased by 20% over fasting on day 56; further improved to 834.1 pmol/L at day 120 (undetectable at baseline)	Began to decline after 2 weeks; achieved complete insulin independence on day 75 and remained so during the 1-year follow-up
[25]	2015	Autologous BM-MSCs	9	No significant difference between the MSC group and control group		No significant difference between the MSC group and control group	Maintained in 6/9 patients of the MSC group, but decreased in 8/9 patients in the control group	No significant difference between MCS and control groups
[26]	2022	Autologous BM-MSCs	11	Decreased by 1.46 percentage points compared with the control group at 1 yeara; the early treatment group had a significant reduction of 2.95b, 1.69a, and 1.40a percentage points relative to the late treatment group at 3, 6, and 9 months, respectively		Higher than that in the control group, but with no significant difference; the early treatment group had a significant increase of 0.58 ng/mLa, 0.46 ng/mLa, and 0.56 ng/mLa than the late treatment group at 3, 6, and 9 months, respectively	Higher than that in the control group, but with no significant difference	Increased in both groups, with no significant difference between two groups
[19]	2013	Allogeneic WJ-MSCs	15	Decreased by 1.3 percentage points (the lowest level) at month 6 (6.8% ± 0.57% to 5.5% ± 0.67%) and maintained a small fluctuation over the following 18 months		Higher than the control group, also higher than the baseline at the end of follow-up, whereas the control group showed a gradual downward trend		3/15 patients discontinued insulin; daily insulin dose was reduced by more than 50% in 8 patients and by 15%-50% in 1 patient
[27]	2016	Allogeneic BM-MSCs	5 (1 patient was lost to follow-up)	3/4 patients maintained a similar or lower level for at least 3 years		Declined slowly in all patients	1 patient rose above the baseline for as long as 1 year	Insulin dose was reduced by 50% in 2/4 patients; 1 patient achieved insulin independence for 3 months
[28]	2022	Allogeneic UC-MSCs and BM-MSCs	14 (4 of BM-MSCs, 10 of UC-MSCs)	Decreased both in BM-MSC and UC-MSC groups, while slightly increased in the control groupa; no significant difference in the reduction between BM-MSCs and UC-MSCs group		Clinical remission (10% increase from baseline in the fasting C-peptide and/or postprandial C-peptide levels) was achieved in 4/14 patientsc, including 1 patient (1/4, 25.0%) in the BM-MSC group and 3 patients (3/10, 33.3%) in the UC-MSC groupc		Reduced relative to the control groupa; no significant difference in the reduction between BM-MSC and UC-MSC groups
[29]	2020	Allogeneic AD-MSCs	8	Lower than control group (6.47% ± 0.86% vs 7.48% ± 0.52%)a	No significant difference between the MSC and control groups		No significant difference between the MSC and control groups	Lower than control group (0.25 ± 0.19 IU/kg vs 0.56 ± 0.23 IU/kg)a; 2/8 patients achieved insulin independence for 4 and 8 weeks, respectively
[30]	2015	Autologous/allogeneic AD-MSCs with hematopoietic stem cells	10 of autologous, 10 of allogeneic	Decreased in both groups with no significant difference		Increased in both groups; higher in the autologous group than in the allogeneic group (0.93 ± 0.24 ng/mL vs 0.46 ± 0.29 ng/mL)a		The mean insulin dose decreased by 37.93% in the autologous group and by 33.11% in the allogeneic group

^aP < 0.05.

^bP < 0.001.

^cP > 0.05.

No.: Number of stem cell-treated patients; SCs: Stem cells; HbA1c: Glycated hemoglobin A1c; TIR: Time in range; hESCs: Human embryonic stem cells; hiPSCs: Human induced pluripotent stem cells; BM-MSCs: Bone marrow-derived mesenchymal stem cells; MSC: Mesenchymal stem cell; WJ-MSCs: Wharton’s jelly-derived mesenchymal stem cells; UC-MSCs: Umbilical cord-derived mesenchymal stem cells; AD-MSCs: Adipose-derived mesenchymal stem cells.