Safety and feasibility of umbilical cord mesenchymal stem cells in treatment-refractory systemic lupus erythematosus nephritis: time for a double-blind placebo-controlled trial to determine efficacy

Table 1 Overview of open-label phase I/II studies to evaluate mesenchymal stem cells (1 × 10 ⁶ per kg) in treatment-refractory systemic lupus erythematosus

Authors (date)	ClinicalTrials.gov protocol number	Study design/duration of follow-up	Number of patients	MSC type/regimen	Conditioning	Safety: deaths/serious infection	PD marker^a	Efficacy
Sun et al. [2]	NR	Single-arm/ median of 8.25 months (range of 3 to 28 months)	16 (15 SLEN)	UC, single infusion	CYC 0.8 to 1.8 mg/kg intravenously, 2 to 4 days	0/0	Percentage of Treg cells increased at 3 months (P = 0.03)	‘Decreasing SLEDAI and proteinuria^b in all patients’
Liang et al. [3]	NCT 00698191	Single-arm/17.2 ± 9.5 months	15 SLEN	BM, single infusion	Included in protocol, but NR	0/0	Percentage of Treg cells increased at 1 week and 3 and 6 months (P <0.05)	‘Decreasing SLEDAI and proteinuria^b in all patients’
Wang et al. [4]	NCT 00698191	Unblinded-randomized, 2-arm/12 months	58 (~88% SLEN)	BM, UC, single versus 2× (7 days apart)	CYC 10 mg/kg per day, day 4, 3, and 2	1/NR	ND	CR single: 16/30 (53%); double: 8/27 (29%)
Wang et al. [5]	NR	Single-arm/mean of 27 months	87 (84% SLEN)	BM, UC, single infusion, 18 patients retreated at relapse	CYC 10 mg/ kg/day, day 4, 3, and 2	5/NR	ND	CR in 23/83, relapse 10/83
Wang et al. [1]	^cNCT 01741857	Single-arm	40 (38 SLEN)	UC, 2× infusion, 7 days apart)	No	3/4	ND	MCR 13/PCR 11, 7 relapse

^aPharmacodynamic (PD) markers = increased peripheral blood regulatory T (Treg) cells, balanced T helper 1 (Th1)/Th2 cytokines; ^b[2] baseline (BL) proteinuria 3.1 (±1.2) g/day versus 3 months, 1.3 (±0.9) g/day (P <0.001, n = 15); [3] BL proteinuria 2.7 (±1.2) g/day versus 6 months, 0.9 (±0.8) g/day (P <0.01, n = 12); ^cprotocol described at ClinicalTrials.gov consistent with this study, but not explicitly noted in report. BM, bone marrow; CR, complete remission; CYC, cyclophosphamide; MCR, major clinical response; MSC, mesenchymal stem cell; ND, not done; NR, not reported; PCR, partial clinical response; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; SLEN, systemic lupus erythematosus nephritis; UC, umbilical cord.

ISSN: 1478-6362