Table 1.

Registered clinical trials testing the efficacy of MSCs in kidney

Recipients	Source	Administration route	Primary endpoint	Secondary endpoint	Dose	Follow-up period	Trial registration	Ref.
AKI
Patients with high risk of developing AKI following heart surgery	Allogeneic BM-MSCs	Intra-aortic	Safety, as documented by comparing the incidence of adverse events, serious adverse events, and complications	Efficacy of MSC administration for prevention and treatment of postoperative AKI	NA	6 months	NCT00733876	[159, 160]
Patients undergoing cardiac surgery with evidence of early AKI	Allogeneic MSCs	Intra-aortic	The time to recover kidney function was defined as return of postintervention creatinine levels to baseline	Included all-cause mortality or provision of dialysis at 30 and 90 days post-study drug administration	2 × 106cells/kg	90 days	NCT01602328	[161]
CKD
CKD patients (eGFR 15–60 mg/ml)	Supernatants of hCB-MSCs	Intravenous and intra-arterial	The safety of the therapy through for a period of 1 year	The efficacy of treatment assessed by duplication of eGFR or 50% reduction of serum creatinine from the baseline level of each patient	100 μg/kg	12 months	NA	[162]
Type 2 DN patients	Allogeneic BM-MPCs	Intravenous	The safety and tolerability, including the number and percentage of subjects with adverse events and serious adverse events, clinically significant values and shifts from baseline in vital signs, and clinical laboratory tests	Efficacy change from baseline in eGFR and directly measured GFR by 99Tc-DTPA plasma clearance at 12 weeks post-infusion	150 × 106 or 300 × 106 cells/kg	60 weeks	NCT01843387	[163]
CKD patients (eGFR 20–40 ml/min/1.73 m2)	Autologous AT-MSCs	Intravenous	The eGFR and quantitative 24-h urinary protein excretion rate for a period of 12 months	Clinical or biochemical changes suggestive of treatment-associated adverse events or warnings	1 × 106 cells/kg	12 months	NA	[164]
CKD patients (eGFR 25–60 ml/min/1.73 m2)	Autologous BM-MSCs	Intravenous	The safety was measured by number and severity of adverse events	Decrease in the rate of decrease in eGFR	1–2 × 106 cells/kg	18 months	NCT02195323	[165]
RVD patients	Autologous AD-MSCs	Intra-arterial	1. Change in kidney function 2. Safety of mesenchymal stem cell infusion	Decrease in kidney inflammation	1.0 × 105 or 2.5 × 105cells/kg	3 months	NCT02266394	[166]
ADPKD patients	Autologous BM-MSCs	Intravenous	The numbers, type, and severity of AEs	Changes in eGFR from baseline to 12 months after cell infusion	2 × 106 cells/kg	12 months	NCT02166489	[167]
Patients with active and refractory LN	Allogeneic BM-MSCs (n = 23) or hUC-MSCs (n = 58)	Intravenous	Remission of nephritis (CR and PR) as well as renal flares within 12 months	SLEDAI score for disease activity, BILAG score of renal system, and changes in renal function, serum albumin, and anti-dsDNA antibody levels pre- and post-MSCT	1 × 106 cells/kg	12 months	NA	[173].
Patients with class III or IV LN	hUC-MSCs	Intravenous	Remission of nephritis was defined as stabilization or improvement in renal function, urinary red blood cells of less than 10 per hpf, and reduction of proteinuria to less than 3 g/day if baseline proteinuria was more than 3 g/day or at least a 50% reduction in proteinuria or to less than 1 g/day if baseline proteinuria was in the subnephrotic range	Improvement in SLEDAI and BILAG scores, complement concentration, anti-dsDNA (double-stranded DNA) antibody and ANA titers, death and commencement of permanent dialysis or renal transplantation	2 × 108 cells/kg	12 months	NCT01539902	[174]
Renal transplantation
Kidney transplant recipients	Autologous BM-MSCs	Intravenous	Assessing the percentage of inhibition of memory T cell response and/or naive T cell response, the induction of donor-reactive T cell anergy, and the appearance in the peripheral blood of regulatory T cells	Safety parameters related to MSC infusion, graft function, graft rejection	2 × 106/kg	1 year	NCT00752479	[175, 177]
Kidney transplant recipients	Allogeneic BM-MSCs	Intravenous	Adverse effects of MSC infusion as well as infectious and malignant complications at 1 year	Effect of MSCs on graft outcomes and immunity as well as the occurrence of anti-MSC-DSAs	1.5 × 106–3 × 106 cells/kg	1 year	NCT01429038	[179]
Kidney transplant recipients	Autologous BM-MSCs	Intravenous	Changes of regulatory T cells and serum creatinine	Changes T cell proliferation, regulatory T cells, memory T cells, B cells, and cytokine profile	0.2–0.8 × 106/kg	6 months	NCT02409940	[180]
Kidney transplant recipients	Autologous BM-MSCs	Intravenous	1. Rate of (serious) adverse events in the study population 2. Feasibility: determination of the number of expanded MSCs in relation to the amount of BM collected, number of passages required, and time to reach study target doses	1. Presence of late acute rejection (at 6-month biopsy when compared with 4-week biopsy) 2. Sirius red staining for renal cortical matrix accumulation. 3. Immunologic response before and after MSC infusion	1 × 106 cells/kg	24 weeks	NCT00734396	[181]
Kidney transplant recipients	Autologous BM-MSCs	Intravenous	1-year incidence of acute rejection and renal function eGFR	Patient and graft survival and incidence of adverse events	1–2 × 106 cells/kg	30 months	NCT00658073	[183]

AD-MSCs adipose-derived mesenchymal stem cells, ADPKD autosomal dominant polycystic kidney disease, AEs adverse events, anti-MSC-DSAs anti-mesenchymal stem cell donor-specific antibodies, AT-MSCs adipose tissue-derived MSCs, BM-MSCs bone marrow-derived mesenchymal stromal cells, BM-MPCs bone marrow-derived mesenchymal precursor cells, CR complete remission, DN diabetic nephropathy, eGFR estimated glomerular filtration rate, hUC-MSCs human umbilical cord-derived mesenchymal stem cells, hCB-MSCs human cord blood mesenchymal stem cells, LN lupus nephropathy, MPCs mesenchymal precursor cells, NA not applicable, PR partial remission, RVD renovascular disease, SAEs severe adverse events