Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes

Table 2

Summary of clinical trials using MSCs to treat patients with T2DM.

Year/sample size	MSC sources	MSC dose (cells)	Interventions	Outcome measurements	References/NCT number
2008	BM-SCs	Unknown	Intrapancreatic injection	Fasting glucose, HbA1c, and insulin requirements decreased; fasting C-peptide and C-peptide/glucose ratio increased	Estrada et al. [38]
2014	Autologous BM-SCs	cells/kg	Intrapancreatic injection	The insulin requirement decreased; HbA1c increased modestly and nonsignificantly; glucagon-stimulated C-peptide increased significantly	Bhansali et al. [41]
2016	WJ-MSCs	cells/kg	Two intravenous infusions, with a one-month interval	No serious adverse reactions; improvements in C-peptide and insulin dosage in the MSC group	Hu et al. [42]
2011	Allogeneic HP-MSCs	cells/kg	Three intravenous infusions of PDSCs, with a one-month interval	No acute adverse events, average insulin dosage, C-peptide, and HbA1c improved after treatment	Jiang et al. [16]
2010	Allogeneic WJ-MSCs	cells/kg	Infused into the peripheral vein on day 5; delivered directly to the pancreas via he splenic artery using endovascular catheters on day 10	Fever, subcutaneous hematoma, and headache were observed; mild improvement in HbA1c, insulin dosage, and fasting C-peptide; markers of systemic inflammation were decreased	Liu et al. [40]
2014	UC-MSCs	cells/kg	UC-MSCs were intravenously transfused three times. All patients were followed up in the first, third, and sixth months	FBG and PBG were significantly reduced; plasma C-peptide levels and regulatory T cell numbers were numerically higher	Kong et al. [43]
2014	BM-MNCs	cells/kg	Pancreatic artery infusion in 10 min	No acute adverse events; the area under the curve of C-peptide was significantly improved	Wu et al. [44]
2015	Allogeneic BM-MSCs	0.3- cells/kg	Subjects were randomized to receive one of the following three rexlemestrocel-L doses or placebo in a 3 : 1 ratio using a sequential, escalating dose cohort paradigm	No acute adverse events; HbA1c was reduced at all time points after week 1	Skyler et al. [45]
2016	Allogeneic BM-MSCs	150- cells/kg	Treatment was administered by intravenous infusion on day 0 following baseline assessments; two sequential dose cohorts, to receive rexlemestrocel-L or placebo; study duration was 60 weeks	No acute adverse events; improved eGFR and mGFR at week 12	Packham et al. [46]
2016	UC-MSCs	cells/kg	The hUC-MSCs were transplanted by infusing cells/kg via the pancreatic artery directed on day 1, followed by infusing cells/kg through the peripheral vein on days 8, 15, and 22	ΔCP30/ΔG30 and AUCCP180 increased; FPG, 2hPG, HbA1c, and HOMA-IR reduced	Li et al. [39]
2017	Autologous BM-MSCs and autologous BM-MNCs	MSCs: cells/kg; MNCs: 10^9 per patient	Intrapancreatic infusion	Significant reduction in insulin requirement; significant increase in the second-phase C-peptide response and insulin sensitivity index	Bhansali et al. [47]
August 2010	BM-MSCs	Unknown	BM-MSCs are transplanted through the pancreatic artery percutaneously on day 0; BM-MSCs are transplanted intravenously on days 7 and 14	Unknown	NCT01142050
January 2011	Autologous BM-MNCs; Autologous BM-MSCs	Unknown	Three groups treated with BM-MSCs, BM-MNCs, and insulin	Unknown	NCT01719640
January 2013	UC-MSCs	Intravenous/infusion treatment	Unknown	Unknown	NCT02302599
September 2015; Recruiting	Injectable collagen scaffold with hUC-MSCs	intracavernous injection	Intracavernous injection of an injectable collagen scaffold combined with 15 million hUC-MSCs; intracavernous injection of 15 million hUC-MSCs	Unknown	NCT02745808
November 2017	Autologous BM-MSCs	Unknown	Pancreatic artery infusion	Unknown	NCT03343782
April 2019; Recruiting	Autologous BM-MNCs and allogeneic UC-MSCs	UC-MSC: 1- cells/kg intravenous infusion	Unknown	Unknown	NCT03943940
November 2019; Recruiting	hUC-MSCs	cells/kg peripheral intravenous infusion	Unknown	Unknown	NCT04216849

Abbreviations: BM-SCs: bone marrow stem cells; WJ-MSCs: Wharton’s jelly-derived mesenchymal stem cells; UC-MSCs: umbilical cord mesenchymal stem cells; BM-MNCs: bone marrow mononuclear cells; BM-MSCs: bone marrow mesenchymal stem cells; HP-MSCs: hypoxia preconditioned mesenchymal stem cells; PDSCs: placenta-derived stem cells; FBG: fasting blood glucose; PBG: postprandial blood glucose; eGFR: estimated glomerular filtration rate; mGFR: measured glomerular filtration rate; 2hPG: postload glucose; FPG: fasting plasma glucose; AUCCP180: amount of C-peptide secretion function; HbA1c: hemoglobin A1c; HOMA: homeostatic model assessment; IR: insulin resistance.