Mesenchymal Stem Cells: An Excellent Candidate for the Treatment of Diabetes Mellitus

Table 3

Clinical studies of MSC therapy for T2DM.

Publication	Cell resource	Injection method	Injection dose	Number of injections	Follow-up time	Efficacy Evaluation Index	Results	Adverse events	Study design
Liu et al. [42]	WJ-MSC	Splenic artery injection; intravenous injection	1 × 10^6 cells/kg	Twice	12 months	HbA1c, C-peptide, FBG, PBG, insulin requirements, inflammatory markers, T lymphocyte counts	WJ-MSC transplantation significantly decreased the levels of glucose and glycated hemoglobin, improved C-peptide levels and beta cell function and reduced markers of systemic inflammation and T lymphocyte counts.	Fever, subcutaneous hematoma, nausea, vomiting, and headache	Open, single-center, nonrandomized study
Bhansaliet al. [43]	Autologous BM-MSC	Superior pancreatic injection; antecubital vein injection	1 × 10^6 cells/kg	Twice	12 months	Insulin requirements, HbA1c, C-peptide	BM-MSC therapy resulted in a significant decrease in the insulin dose requirement along with an improvement in the stimulated C-peptide levels in T2DM.	No obviously adverse reactions	Randomized, single-blinded, placebo-controlled study
Bhansali et al. [44]	Autologous BM-MSC and autologous BM-MNC	Superior pancreatic injection; antecubital vein injection	MSCs:1 × 10^6 cells/kg; MNCs: 1 × 10^9 cells/kg	Twice	12 months	ISI, insulin, HbA1c, C-peptide, HOMA-IR, HOMA-β, HOMA-S, GLUT-4, IRS-1	Both autologous BM-MSCs and autologous BM-MNCs resulted in sustained reduction in insulin doses in T2DM and improved insulin sensitivity with MSCs and increased C-peptide response with MNCs.	Nausea and vomiting, local extravasation, minor hypoglycemia	Randomized, single-blinded, placebo-controlled study
Kong et al. [45]	UC-MSC	Vein injection	1 × 10^6 cells/kg	Three times	6 months	FPG, PBG, HbA1c, C-peptide, subsets of T cells	FBG and PBG of the patients in the efficacy group were significantly reduced after UMSC transfusion.	Slight transient fever	Randomized, single-blinded, placebo-controlled study
Chen et al.[46]	UC-MSC	Superior pancreatic injection; antecubital vein injection	1 × 10^6 cells/kg	Four times	6 months	FPG, PBG, HbA1c, C-peptide, HOMA-IR	The FPG, 2hPG, and HbA1c levels were significantly improved in the group with MSCs.; Liraglutide treatment in combination with hUC-MSCs improves glucose metabolism and the β-cell function in T2DM.	Hypoglycemia event	Randomized, single-blinded, placebo-controlled study
Skyler er al. [47]	Allogeneic BM-MPS	Intravenous infusion	0.3/1/2 × 10^6 cells/kg	Once	12 weeks	HbA1c, FPG	At week 12, the HbA1c target of <7% was achieved, respectively 13.3%, 6.7%, 33.3%; at week 12, the FPG showed no trends across treatment groups.	No serious adverse events	Multicenter, randomized, single-blind, placebo-controlled
Jiang et al. [48]	Placenta-MSCs	Intravenous infusions	1.35 × 10^6 cells/kg	Three times	6 months	Insulin requirements, C-peptide, HbA1c	The daily mean dose of insulin requirements decreased, and the C-peptide level was increased after therapy.		Nonrandomized study

BM-MPCs: bone marrow-derived mesenchymal precursor cells, TNF-α: tumor necrosis factor-α, ISI: insulin sensitivity index, HOMA-IR: homeostatic model assessment of insulin resistance, HOMA-β: homeostatic model assessment of β-cell function, HOMA-S: homeostatic model assessment of insulin sensitivity, GLUT-4: glucose transporter type 4, and IRS-1: insulin receptor substrate-1.