Human umbilical cord mesenchymal stem cells for psoriasis: a phase 1/2a, single-arm study

Abstract

Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4⁺ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4⁺ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4⁺ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957.

Fig. 1

Flowchart of the study

Fig. 2

The figure showed three outcome measures of the 6 responders including PASI score, BSA and PGA. a PASI score; b BSA; c PGA

Fig. 3

Representative skin images of 3 patients before and after treatment

Fig. 4

Frequencies and numbers of T lymphocyte subsets in PB of HC and patients with psoriasis pre- and post-UMSCT. a Frequencies and numbers of CD4⁺ memory T cells (CD45RO⁺ in CD3⁺CD4⁺). b Frequencies and numbers of Tregs (CD25⁺CD127^-/low in CD3⁺CD4⁺). c Frequencies and numbers of CD8⁺ TCM cells (CCR7⁺CD45RA^- in CD3⁺CD8⁺). (HC, n = 15; Patients, n = 17; ns, no significant, VS HC; *P < 0.05, **P < 0.01, ***P < 0.001 VS Pre-UMSCT); d Frequencies of Th1, Th2, Th17 and the ratio of Th1/Th2. (HC, n = 15; Patients, n = 17; *P < 0.05, VS HC; ns, no significant, VS Pre-UMSCT

Fig. 5

The inflammatory factors in the serum in HC and psoriasis patients pre- and post-UMSCT. a Serum TNF-α concentration. b Serum IL-6 concentration. c Serum IL-1β concentration. d Serum IL-17 concentration in HC, all psoriasis patients and responders pre- and post-UMSCT. (n = 17, **P < 0.01, ***P < 0.001, vs Pre-UMSCT)

Fig. 6

Baseline immune indices in PB in response group and no-response group. a Baseline level of CD4+TCM cells. b Baseline level of Tregs. c Baseline level of the ratio of Treg/Th17 (response group: n = 6, no-response group: n = 11, *P < 0.05; **P < 0.01)

Fig. 7

The changes in T lymphocyte subsets in responders pre- and post-UMSCT. a–e Changes of frequencies and numbers of CD4 naive T, CD4+ TCM, CD4+ memory T, Treg and CD8+ TCM cells in PB in responders (n = 6, *P < 0.05, **P < 0.01, ***P < 0.001); f−g Changes of frequencies of Th1, Th2, Th17 and Th1/Th2 and Treg/Th17 in PB in responders (n = 6, *P < 0.05, **P < 0.01)