Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease: A Review of the Studies Using Syngeneic, Autologous, Allogeneic, and Xenogeneic Cells

Table 2

Autologous MSC-based clinical trials.

MSC source	DM type	Age (years)	Time of DM	Number of patients	Number of injections/route of delivery	Number of cells injected	Follow-up (m)	Results	Adverse events	Ref
BM	1	<8 y	<2 m	2	Single dose, liver	/kg	12	C-peptide; FBG, HbA1c; Negative values of ICA, GAD and anti-insulin antibody levels	None	[161]
BM	1	18-40 y	<3 w	10 treated with insulin and 10 treated with insulin+MSCs	Single dose, IV	2.1-/kg (median /kg)	12	C-peptide after mixed-meal tolerance test; HbA1c, insulin dose, fasting C-peptide	None	[162]
AT-ISC-MSC+BM-HSC; conditioning	1	Group 1:  y; Group 2:  y	Group 1:  y; Group 2:  y	Group 1: autologous AT-ISC-MSC+BM-HSC; Group 2: allogeneic AT-ISC-MSC+BM-HSC from healthy nondiabetic donors ( each)	Single dose, portal+intrathymus+SC	Group 1: AT-ISC-MSC-/kg; Group 2: AT-ISC-MSC-/kg	24	Autologous versus allogeneic: (i) Allogeneic: ↓ insulin requirement up to 6 months and ↓ postprandial blood sugar from months 1-24; (ii) Autologous: ↑ C-peptide from months 15-24; (iii) Allogeneic = autologous: HbA1c, FBG, GAD antibody	None	[157, 158]
BM	2	30-60 y	≥5 y	BM-MSC versus BM-MNCs versus control group (antidiabetic drugs) ( each)	Single dose, superior pancreatic-duodenal artery	MSCs: /kg; MNCs:	12	Insulin and HbA1c in 60% of individuals (BM-MSC and BM-MNC); HOMA indexes; Insulin sensitivity index+insulin receptor substrate-1 gene expression in muscle (BM-MSC); Second phase C-peptide response during hyperglycaemic clamp (BM-MNCs)	Nausea and vomiting ()	[163]
BM	2	37-67 y (52.9 y)	2-15 y (7.15 y)	NPR (); PR ()	Single dose, IV	/kg	6	FBG, hypersensitivity C-reactive protein; HbA1c, plasma IL-6; Macular thickness and improvement in best corrected visual acuity (proliferative retinopathy group)	None	[164]

AT-ISC-MSC: adipose-derived insulin-secreting mesenchymal stem cells; BM-HSCs: bone marrow-derived hematopoietic stem cells; BM-MNCs: bone marrow-derived mononuclear cells. Autoantibodies to β-cells: GAD65 (glutamic acid decarboxylase) and IA2 antibodies. FBG: fasting blood glucose; HbA1c: glycated haemoglobin; NPR: nonproliferative retinopathy; PR: proliferative retinopathy; SC: subcutaneous; IU: International Units; IV: intravenous; w: week; m: month; y: years.