Mesenchymal Stem Cell Therapy for Inflammatory Skin Diseases: Clinical Potential and Mode of Action

Shin, Tae–Hoon; Kim, Hyung–Sik; Choi, Soon Won; Kang, Kyung‐Sun

doi:10.3390/ijms18020244

Cited by 83 publications

(74 citation statements)

References 163 publications

(166 reference statements)

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“…Up to now, no direct evidence is available on the clinical relevance of preclinical results with exosomes derived from human cells in animal models. However, results from phase I/IIa clinical trials with human umbilical cord blood (UCB)-derived MSCs was confirmed the therapeutic efficacy of human UCB-MSCs observed in animal studies [69]. Since it has been established that the therapeutic effects In conclusion, the present study highlights a hitherto unappreciated role of ASC-exosomes in AD, and defines a unique role by which the ASC-exosomes repair defective epidermal permeability barrier functions.…”

Section: Discussionsupporting

confidence: 72%

Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis

Shin

Ha²,

Kim³

et al. 2020

Cells

129

127

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Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes’ effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD.

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Section: Discussionsupporting

confidence: 72%

Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis

Shin

Ha²,

Kim³

et al. 2020

Cells

129

127

View full text Add to dashboard Cite

show abstract

“…Mesenchymal stem cells (MSCs) are stromal-derived nonhaematopoietic progenitor cells residing in several adult and neonatal tissues as bone marrow, umbilical cord, adipose tissue, amniotic fluid, placenta, dental pulp and skin [15]. MSCs have been revealed to possess distinct immunemodulatory properties, which induce immune tolerance in different inflammatory conditions [16].…”

Section: Discussionmentioning

confidence: 99%

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

Campanati

Orciani

Sorgentoni

et al. 2018

Clinical and Experimental Immunology

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Psoriasis microenvironment, characterized by an imbalance between T helper type 1 (Th1)/Th17 and Th2 cytokines and also influences the mesenchymal stem cells (MSCs) phenotypical profile. MSCs from healthy donors (H-MSCs) can exert a strong paracrine effect by secreting active soluble factors, able to modulate the inflammation in the microenvironment. To evaluate the influence of H-MSCs on MSCs from psoriatic patients (PsO-MSCs), H-MSCs and PsO-MSCs were isolated and characterized. Indirect co-culture of H-MSCs with PsO-MSCs was performed; effects on proliferation and expression of cytokines linked to Th1/Th17 and Th2 pathways were assayed before and after co-culture. The results show that before co-culture, proliferation of PsO-MSCs was significantly higher than H-MSCs (P < 0·05) and the levels of secreted cytokines confirmed the imbalance of Th1/Th17 versus the Th2 axis. After co-culture of H-MSCs with PsO-MSCs, healthy MSCs seem to exert a 'positive' influence on PsO-MSCs, driving the inflammatory phenotypical profile of PsO-MSCs towards a physiological pattern. The proliferation rate decreased towards values nearer to those observed in H-MSCs and the secretion of the cytokines that mostly identified the inflammatory microenvironment that characterized psoriasis, such as interleukin (IL)-6, IL-12, IL-13, IL-17A, tumour necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (G-CSF), is significantly lower in co-cultured PsO-MSCs than in individually cultured PSO-MSCs (P at least < 0·05). In conclusion, our preliminary results seem to provide an intriguing molecular explanation for the ever-increasing evidence of therapeutic efficacy of allogeneic MSCs infusion in psoriatic patients.

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“…Benefiting from the ease of diagnosing, applying topical treatment and monitoring their evolution due to their superficial location, skin inflammatory disorders represent an increasingly pursued research focus. The development of animal models for these disorders has aided in the investigation of the pathophysiological processes involved, leading to a better understanding of the course of disease and possible mechanisms that may limit, or even revert the development of the illness [103][104][105]. The high impact on the patients' lives and the healthcare system has prompted the research of new treatments, among which cannabinoids are regarded with growing interest due to their initial favorable results and limited adverse effects.…”

Section: Cannabinoids' Role In Inflammatory Skin Disordersmentioning

confidence: 99%

Cannabinoids in the Pathophysiology of Skin Inflammation

et al. 2020

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Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component. However, various studies cite conflicting results concerning the cellular mechanisms involved, while others suggest that cannabinoids may even exert pro-inflammatory behaviors. This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer. In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances. Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.

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Mesenchymal Stem Cell Therapy for Inflammatory Skin Diseases: Clinical Potential and Mode of Action

Cited by 83 publications

References 163 publications

Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis

Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

Cannabinoids in the Pathophysiology of Skin Inflammation

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