Novel sponge formulation of mesenchymal stem cell secretome and hyaluronic acid: a safe and effective topical therapy for Psoriasis vulgaris

Abstract

Background: Psoriasis vulgaris is the most common form of psoriasis, yet current treatments often lead to significant side effects, resulting in a high rate of therapy desertion. Here, we explored a novel therapeutic approach using the secretome from Wharton Jelly-derived mesenchymal stem cells, biologically stabilized and enhanced with hyaluronic acid (HA), its presentation is an easy-to-apply topical sponge. This formulation had previously demonstrated efficacy in vitro and in experimental psoriasis mouse models.

Methods: In vitro characterization studies included dynamic light scattering, nanoparticle tracking analysis, optical/electronic microscopy, microbiological experiments, and angiogenic capacity (HUVEC cells). In vivo studies included angiogenic capacity in chicken embryo chorioallantoic membrane (CAM), safety (hypersensitive and healthy volunteers), and efficacy (double-blinded and randomized patients).

Results: We demonstrated the presence of spherical exosomes (164 ± 87 nm, PDI of 0.38, and 1.5 × 10⁷ particles/mL) within the selected secretomes, which exhibited significant proangiogenic activity in HUVEC cells and in a CAM assay. The secretome-containing sponges displayed distinct physicochemical properties, such as the absence of nitrogen and reduced carbon and oxygen content, resulting in a more cross-linked material with thinner fibers. These characteristics extended the dispersion time in aqueous media. Microbiological testing confirmed sterility in the packed, ready-to-use secretome-HA sponges after 3 months of storage. To assess safety, we selected doses (based on total protein content) that were applied to three patients with atopic dermatitis (42 µg of protein, patch test, 5 days) and four healthy volunteers (210 µg, 15 days) with no observed adverse topical or systemic effects. In a 30-day efficacy study, 12 patients with bilateral psoriasis exhibited up to a 33% reduction in mPASI scores and a 41% decrease in plaque size. Additionally, transepidermal water loss (TEWL) was reduced by up to 30%, while skin elasticity/flexibility improved by 43%.

Conclusions: These findings suggest that the topical application of the secretome-HA sponge is a safe and effective therapeutic option for alleviating symptoms of psoriasis vulgaris.

Trial registration: SSMN, SSMN047/2021. Registered 27 October 2021, https://www.ssmn.cl/comite_etica.php .

Keywords: Exosomes, hyaluronic acid, Psoriasis vulgaris; MSC-based therapy, cutometer; Mesenchymal stem cell; Secretome.

Fig. 1

Characterization of exosomes isolated from the secretomes. (a, b) STEM images of exosomes at 60,000X and 120,000X magnifications, respectively, showing morphological characteristics. (c) Hydrodynamic size and concentration of exosomes (particles/mL) analyzed using NTA. (d) Size distribution of the main exosome fractions identified (n = 3)

Fig. 2

Proangiogenic activity of hWJ-MSC-derived exosomes in vitro and in vivo. (a1) Microscopy images of the HUVEC tubule formation assay after 4 h of incubation with hWJ-MSC exosomes (bar = 6 mm). (a2) Quatification of branches, and (a3) tubule formation by HUVEC cells exposed to hWJ-MSC exosomes (*p < 0.05, permutation test). (2b1) Microscopy images of the blood vessel formation in the CAM assay after 12 days of incubation (bar = 3 mm). (2b2) Represent the quantification of the number of blood vessels for different conditions: VEGF 50 ng/mL (positive control), PBS (negative control), and exosomes 20 µg/mL (*p < 0.05, one-way ANOVA) (n = 10)

Fig. 3

Secretome-HA and HA sponge appearance (nude eye, electronic microscopy, and optical microscopy). a1) Secretome-HA 70 in individual packaging, a2) Unpackaged, ready-to-use secretome-HA 70. Scanning electron microscopy: b1) HA sponge at 400X magnification, (b2) HA sponge at 2000X magnification, (b3) Secretome-HA 70 at 400X magnification, (b4) Secretome-HA 70 at 2000X magnification. c) Optical microscopy of sponges: c1) HA sponge, c2) HA sponge with 75 µL of water until dissolution at 66 s, c3) Secretome-HA 70, c4) Secretome-HA 70 with 75 µL of water until dissolution at 200 s. (n = 3)

Fig. 4

Safety assessment of the Secretome-HA sponge. a) Protocol 1: Evaluation in three patients with atopic dermatitis (named as ADP1, 2 and 3, respectively) after 1, 2 and 5 days post- application of allergens/formulations. The application sites were: I: HA sponge; II: secretome-HA 42; III: physiological serum IV: control (no allergen). b) Protocol 2: Evaluation in four healthy volunteers (named as HV1, 2, 3, and 4, respectively) receiving daily application of the secretome-HA 210 sponge for 15 days. The framed area marks the treated site, which exhibits a similar appearance to the untreated opposite arm

Fig. 5

Efficacy of the Secretome-HA sponge in psoriasis treatment. (a) Schematic representation of the 30-day efficacy protocol in patients with psoriasis. (b) TEWL variation following secretome-HA sponge treatment shows a similar trend to the healthy, non-lesioned skin (considering skin close to the lesion evaluated, in the same body region) treated with a standard moisturizing lotion. (c) The percentage of elasticity/flexibility variation (R0) is higher with the use of secretome-HA 18 + 70 and HA sponge. (d) Secretome-HA 18 + 70 effectively reduces mPASI. (e) The combination of secretome-HA 18 + 70 is effective in reducing the size of plaques (n = 7). The significant differences in a, b c, and d are given by the comparison of each parameter with the zero change condition (Kruskal Wallis test, *p < 0.1; **p < 0.05, ***p < 0,01). (f) Relative increase in TEWL, mPASI, plaque size, and R0, expressed as the “secretome-HA 18 + 70 / HA sponge” ratio

Fig. 6

Representative clinical outcomes of patients treated with secretome-HA. Images of two patients treated with secretome-HA 18 for 15 days followed by secretome-HA 70 for an additional 15 days. (a) Day 1: Psoriatic plaque on the instep, characterized by severe erythema, moderate to severe induration, and mild desquamation. Day 30: The plaque shows mild erythema and induration, with no visible desquamation. (b) Day 1: Psoriatic plaque on the thigh, with moderate erythema, induration and mild desquamation. Day 30: Induration and desquamation completely resolve. The remaining erythema is post-inflammatory and does not contribute to the mPASI