Current advances of stem cell-based therapy for kidney diseases

Table 1 Completed clinical trials of mesenchymal stem cell- and endothelial progenitor cells -based therapies in kidney diseases

Ref.	Condition or disease	Trial registration	Source	Main findings
Togel et al[159], Westenfelder et al[160]	Patients with a high risk of developing AKI after undergoing cardiac surgery	NCT00733876	Allogeneic BM-MSCs	MSC infusion was safe
				None of the patients developed postoperative AKI or subsequent loss of kidney function
				Protection against early and late post-surgery kidney function deterioration
				Reduction in length of hospital stay
Swaminathan et al[161]	Patients who experienced AKI 48 hr after cardiac surgery	NCT01602328	Allogeneic BM-MSCs	No significant difference between groups in 30-d all-cause mortality or dialysis
				No reduction in the time to recover kidney function
				No difference in adverse events between groups
Makhlough et al[164]	CKD	NCT02195323	Autologous BM-MSCs	MSC infusion was safe and tolerated.
				No significant changes in eGFR and SCr
Villanueva et al[162]	CKD	NA	Autologous AD-MSCs	MSC infusion was safe and not associated with adverse effects
				Statistically significant improvement in urinary protein excretion but not in GFR
Lee et al[178], Yang et al[179]	CKD at stage III or IV	NA	Autologous CD34+ EPCs	MSC infusion was safe and tolerated
				No additional benefit from EPCs up to a follow-up period
				Significantly lower unfavourable clinical outcomes (dialysis or death) in treatment group
Makhlough et al[163]	CKD due to autosomal dominant polycystic kidney disease	NCT02166489	Autologous BM-MSCs	MSC infusion was safe and tolerated
				No significant changes in eGFR and SCr
Packham et al[180]	Diabetic nephropathy (type 2)	NCT01843387	Allogeneic BM-MSCs	MSC infusion was safe and not associated with acute adverse events
				Stabilisation and improvement in eGFR and mGFR
Saad et al[181]	Atherosclerotic renovascular disease	NCT02266394	Autologous AD-MSCs	MSC infusion was safe and well tolerated.
				Increment in cortical perfusion and renal blood flow
				Reduction in renal tissue hypoxia within poststenotic kidney
Sun et al[165], Liang et al[166]	Refractory SLE	NCT00698191	Allogeneic BM-MSCs	MSC infusion was safe and tolerated
				Improvement in disease activity
				Stabilisation in kidney function
Sun et al[167]	Refractory SLE	NCT00698191	Allogeneic UC-MSCs	MSC infusion was safe and tolerated
				Improvement in disease activity
				Stabilisation in kidney function
Wang et al[168]	Refractory SLE	NCT01741857	Allogeneic UC-MSCs	MSC infusion was safe.
				Reduction in proteinuria 24 hr after transplantation, with statistical differences at 9- and 12-mo follow-ups
Deng et al[171]	LN (class III or IV)	NCT01539902	Allogeneic UC-MSCs	No apparent additional effect over and above standard immunosuppression
Barbado at al[170]	Active and refractory LN	NA	Allogeneic BM-MSCs or UC-MSCs	Significant improvement in proteinuria levels during the 1st month after treatment
				The ameliorations were sustained throughout the follow-up period
Tan et al[177]	Kidney transplant	NCT00658073	Autologous BM-MSCs	MSC infusion was not associated with adverse events and did not compromise kidney transplant survival
				Lower incidence of acute rejection
				Reduction in risk of opportunistic infection, and better estimated kidney function at 1 yr
Reinders et al[182]	Kidney transplant	NCT00734396	Autologous BM-MSCs	MSC infusion was feasible and safe
				Increment in incidence of opportunistic infection
Perico et al[172,174]	Kidney transplant	NCT00752479	Autologous BM-MSCs	MSC infusion was safe and feasible
				Allowed enlargement of Treg in the peripheral blood
				Controlled memory CD8+ T cell function
				No major side effects during long-term follow-up
Erpicum et al[176]	Kidney transplant	NCT01429038	Autologous BM-MSCs	MSC infusion was safe
				Increment in regulatory T cell proportion and with improved early allograft function
Perico et al[172-173]	Kidney transplant	NCT02012153	Autologous BM-MSCs	MSC infusion was safe
				Reduction in circulating memory CD8+ T cells and donor-specific CD8+ T-cell cytolytic response
				No major side effects during long-term follow-up
Mudrabettu et al[175]	Kidney transplant	NCT02409940	Autologous BM-MSCs	MSC infusion was safe
				Increment in proliferation of regulatory T cells
				Reduction in proliferation of CD4+ T cell
Pan et al[183]	Kidney transplant	NA	Autologous BM-MSCs	None of the MSC recipients experienced immediate or long-term toxicity from the treatment
				Comparable incidence of acute rejection and similar graft function and survival between control and study groups
				MSCs permitted the use of lower dosages of nephrotoxic calcineurin inhibitors

MSC: Mesenchymal stem cells; EPC: Endothelial progenitor cells; BM-MSCs: Bone marrow derived- mesenchymal stem cells; AKI: Acute kidney injury; CKD: Chronic kidney disease; SCr: Serum creatinine; SLE: Systemic lupus erythematosus UC-MSCs: Umbilical cord-derived mesenchymal stem cells; NA: Not available.