The effects of human dermal–derived mesenchymal stem cells on the keratinocyte proliferation and apoptosis in psoriasis

Abstract

Psoriasis is a common chronic inflammatory skin disease, characterized by epidermal hyperproliferation. Mesenchymal stem cells (MSCs) regulate inflammation and vascular proliferation in the psoriasis lesions. Whether dermal‐derived mesenchymal stem cells (DMSCs), the main MSCs in the dermis, regulate keratinocyte proliferation and apoptosis remains unknown. In the present study, we assessed the proliferation and apoptosis of keratinocytes cocultured with DMSCs isolated from either normal or psoriatic involved skin. Cell growth and apoptotic rates were determined using Cell Count Kit‐8 and annexin V‐FITC staining, respectively. In addition, EDU kit was also used to measure the rate of keratinocyte proliferation. Our results showed that psoriatic DMSCs (pDMSCs) were more potent than normal DMSCs (nDMSCs) in stimulating keratinocyte proliferation. In contrast, the apoptotic rate and expression levels of caspase‐3 protein were lower in pDMSC‐treated than nDMSC‐treated keratinocytes (p < 0.001). Moreover, significantly higher contents of IL‐6, IL‐8, TNF‐α and IFN‐γ were found in the culture medium of pDMSCs than in that of nDMSCs. In conclusion, pDMSCs were more potent than nDMSCs in stimulation of keratinocyte proliferation and secretion of proinflammatory cytokines, but weaker in promoting apoptosis.

PANoptosis signaling enables broad immune response in psoriasis: From pathogenesis to new therapeutic strategies

“…1 D and F). In a previous study, necroptotic and apoptotic cell death was reported in skin lesions from patients with psoriasis [1] , [32] . Additionally, we analyzed the expression of the critical numbers involved in PANoptosis (pyroptosis) signaling in skin lesions of psoriatic patients.…”

“…In psoriasis, evasion of keratinocyte apoptosis plays an important role in facilitating abnormal keratinocyte hyperproliferation [58] , [59] . Subsequently, various potential therapeutic strategies for psoriasis have emerged to promote keratinocyte apoptosis, such as miR-383 [18] , mesenchymal stem cells (MSCs) [32] , and BAY 11–7082 antagonists [60] . Necroptosis is a new type of programmed necrosis that can strongly facilitate the inflammatory response by inducing the manufacture of cytokines and disrupting damage-associated molecular pattern (DAMP) release [61] .…”

Mesenchymal Stem Cells and Psoriasis: Systematic Review

“…Keratinocytes (KCs) play essential roles in both the initiation and maintenance phases of psoriasis since, being a part of the innate immune system, KCs are responsive to multiple triggers. There is mutual crosstalk between MSCs and KCs: on the one hand, high levels of pro-inflammatory cytokines secreted by MSCs induce KCs proliferation, probably via activating the PI3K/AKT signaling pathway [ 18 ] and through the secretion of cytokines such as Epidermal Growth Factor (EGF) [ 19 ] and inhibit their apoptosis due to the reduction in expression levels of caspase-3 [ 20 , 21 ]; it has also been observed that dermal PsO-MSCs contribute to the reduction in the cellular junction, with a consequent alteration in KC differentiation and shortened epidermal turnover time [ 22 , 23 ]. On the other hand, PsO-KCs co-cultured with control MSCs upregulates the expression of c-Myc, GLUT1, SCF, and EGF, resulting in enhanced metabolism and increased proliferation of MSCs, establishing a vicious cycle [ 24 ] ( Figure 2 ).…”

Stem cell therapy as a potential treatment option for psoriasis

“… 16 Several recent studies have investigated the use of MSCs as a possible therapeutic option for psoriasis ( Table 1 ). 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 …”