scholarly journals Stem Cells-Derived Extracellular Vesicles: Potential Therapeutics for Wound Healing in Chronic Inflammatory Skin Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 3130
Author(s):  
Enzo Manchon ◽  
Nell Hirt ◽  
Jean-David Bouaziz ◽  
Nabila Jabrane-Ferrat ◽  
Reem Al-Daccak
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Skin Diseases ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Parental Cell ◽  
Inflammatory Skin Diseases ◽  
Beneficial Effects ◽  
Cell Source ◽  
Inflammatory Skin

Endosome-derived small extracellular vesicles (EVs), often referred to as exosomes, are produced by almost all, if not all, cell types, and are critical for intercellular communication. They are composed of a lipid bilayer associated with membrane proteins and contain a payload of lipids, proteins and regulatory RNAs that depends on the parental cell physiological condition. By transferring their “cargo”, exosomes can modulate the phenotype of neighboring and distant cells. Stem cells (SC) were widely studied for therapeutic applications regarding their regenerative/reparative potential as well as their immunomodulatory properties. Whether from autologous or allogeneic source, SC beneficial effects in terms of repair and regeneration are largely attributed to their paracrine signaling notably through secreted EVs. Subsequently, SC-derived EVs have been investigated for the treatment of various diseases, including inflammatory skin disorders, and are today fast-track cell-free tools for regenerative/reparative strategies. Yet, their clinical application is still facing considerable challenges, including production and isolation procedures, and optimal cell source. Within the emerging concept of “allogeneic-driven benefit” for SC-based therapies, the use of EVs from allogeneic sources becomes the pragmatic choice although a universal allogeneic cell source is still needed. As a unique temporary organ that ensures the mutual coexistence of two allogeneic organisms, mother and fetus, the human placenta offers a persuasive allogeneic stem cell source for development of therapeutic EVs. Advancing cell-free therapeutics nurtures great hope and provides new perspectives for the development of safe and effective treatment in regenerative/reparative medicine and beyond. We will outline the current state of the art in regard of EVs, summarize their therapeutic potential in the context of skin inflammatory disorders, and discuss their translational advantages and hurdles.

scholarly journals Immunomodulatory properties of umbilical cord blood-derived small extracellular vesicles and their therapeutic potential for inflammatory skin disorders

2021 ◽  
Author(s):  
Silvia C Rodrigues ◽  
Renato M S Cardoso ◽  
Patricia C Freire ◽  
Claudia F Gomes ◽  
Filipe V Duarte ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Umbilical Cord Blood ◽  
Skin Diseases ◽  
Therapeutic Potential ◽  
Psoriatic Skin ◽  
Inflammatory Skin Diseases ◽  
Inflammatory Skin ◽  
Anti Inflammatory

Umbilical cord blood (UCB) has long been seen as a rich source of naive cells with strong regenerative potential, likely mediated by small extracellular vesicles (sEV). More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell sEV (herein referred as Exo-101), and explore their therapeutic potential for inflammatory skin diseases. Exo-101 was shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with Exo-101 resulted in an reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, Exo-101 reduced the expression of inflammatory and psoriatic markers IL-6, IL-8, CXCL10, COX-2, S100A7 and DEFB4. In vivo, Exo-101 significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of Exo-101, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.

scholarly journals Anti-Inflammatory and Pro-Differentiating Properties of the Aryl Hydrocarbon Receptor Ligands NPD-0614-13 and NPD-0614-24: Potential Therapeutic Benefits in Psoriasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7501
Author(s):  
Giorgia Cardinali ◽  
Enrica Flori ◽  
Arianna Mastrofrancesco ◽  
Sarah Mosca ◽  
Monica Ottaviani ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Skin Diseases ◽  
Cell Types ◽  
Inflammatory Skin Diseases ◽  
Beneficial Effects ◽  
Aryl Hydrocarbon ◽  
Skin Cell ◽  
Therapeutic Benefits ◽  
Inflammatory Skin ◽  
Factor Α

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor expressed in all skin cell types, plays a key role in physiological and pathological processes. Several studies have shown that this receptor is involved in the prevention of inflammatory skin diseases, e.g., psoriasis, atopic dermatitis, representing a potential therapeutic target. We tested the safety profile and the biological activity of NPD-0614-13 and NPD-0614-24, two new synthetic AhR ligands structurally related to the natural agonist FICZ, known to be effective in psoriasis. NPD-0614-13 and NPD-0614-24 did not alter per se the physiological functions of the different skin cell populations involved in the pathogenesis of inflammatory skin diseases. In human primary keratinocytes stimulated with tumor necrosis factor-α or lipopolysaccharide the compounds were able to counteract the altered proliferation and to dampen inflammatory signaling by reducing the activation of p38MAPK, c-Jun, NF-kBp65, and the release of cytokines. Furthermore, the molecules were tested for their beneficial effects in human epidermal and full-thickness reconstituted skin models of psoriasis. NPD-0614-13 and NPD-0614-24 recovered the psoriasis skin phenotype exerting pro-differentiating activity and reducing the expression of pro-inflammatory cytokines and antimicrobial peptides. These data provide a rationale for considering NPD-0614-13 and NPD-0614-24 in the management of psoriasis.

scholarly journals Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders

2021 ◽  
Vol 22 (18) ◽  
pp. 9797
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Patricia C. Freire ◽  
Cláudia F. Gomes ◽  
Filipe V. Duarte ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Umbilical Cord Blood ◽  
Skin Diseases ◽  
Therapeutic Potential ◽  
Psoriatic Skin ◽  
Inflammatory Skin Diseases ◽  
Inflammatory Skin ◽  
Anti Inflammatory

Umbilical cord blood (UCB) has long been seen as a rich source of naïve cells with strong regenerative potential, likely mediated by paracrine signals. More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell-derived sEV (UCB-MNC-sEV) and explore their therapeutic potential for inflammatory skin diseases. UCB-MNC-sEV were shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with UCB-MNC-sEV resulted in a reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, UCB-MNC-sEV reduced the expression of inflammatory and psoriatic markers IL6, IL8, CXCL10, COX2, S100A7, and DEFB4. In vivo, UCB-MNC-sEV significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of UCB-MNC-sEV, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.

scholarly journals A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders

2020 ◽  
Vol 21 (23) ◽  
pp. 8960
Author(s):  
Ji-Eun Chang ◽  
Min Sik Choi
Keyword(s):  
Skin Diseases ◽  
Skin Disorders ◽  
Cytokine Network ◽  
Inflammatory Skin Diseases ◽  
Beneficial Effects ◽  
Wide Range ◽  
Potential Benefits ◽  
Inflammatory Skin ◽  
Allergic Contact ◽  
Hyperglycemic Effect

Due to its anti-hyperglycemic effect, metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are obese. However, metformin is a drug with a very wide range of pharmacological properties and reports of its therapeutic effect on diseases including inflammation and cancer are increasing. Numerous research groups have reported that metformin has beneficial effects on a variety of inflammatory skin disorders including psoriasis, acanthosis nigricans, acne, hidradenitis suppurativa, and allergic contact dermatitis. According to these reports, in addition to the well-known action of metformin, that is, its anti-hyperglycemic effect, NF-kB inhibition and the resulting alteration to the cytokine network may be the potential targets of metformin. Its anti-hyperandrogenism effect has also been confirmed as the major action of metformin in some inflammatory skin diseases. Moreover, novel regulatory mechanisms, including autophagy and antioxidant processes, have been suggested as promising mechanisms of action for metformin in inflammatory skin disorders.

scholarly journals Therapeutic potential of targeting IL ‐1 family cytokines in chronic inflammatory skin diseases

2022 ◽  
Author(s):  
Laura Calabrese ◽  
Zeno Fiocco ◽  
Takashi K. Satoh ◽  
Ketty Peris ◽  
Lars E. French
Keyword(s):  
Skin Diseases ◽  
Therapeutic Potential ◽  
Inflammatory Skin Diseases ◽  
Inflammatory Skin

scholarly journals Human Amniotic Epithelial Stem Cells: A Promising Seed Cell for Clinical Applications

2020 ◽  
Vol 21 (20) ◽  
pp. 7730
Author(s):  
Chen Qiu ◽  
Zhen Ge ◽  
Wenyu Cui ◽  
Luyang Yu ◽  
Jinying Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cellular Therapy ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Embryonic Stem ◽  
Cell Types ◽  
Epithelial Stem Cells ◽  
Application Procedure ◽  
Cell Source

Perinatal stem cells have been regarded as an attractive and available cell source for medical research and clinical trials in recent years. Multiple stem cell types have been identified in the human placenta. Recent advances in knowledge on placental stem cells have revealed that human amniotic epithelial stem cells (hAESCs) have obvious advantages and can be used as a novel potential cell source for cellular therapy and clinical application. hAESCs are known to possess stem-cell-like plasticity, immune-privilege, and paracrine properties. In addition, non-tumorigenicity and a lack of ethical concerns are two major advantages compared with embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). All of the characteristics mentioned above and other additional advantages, including easy accessibility and a non-invasive application procedure, make hAESCs a potential ideal cell type for use in both research and regenerative medicine in the near future. This review article summarizes current knowledge on the characteristics, therapeutic potential, clinical advances and future challenges of hAESCs in detail.

scholarly journals Crosstalk between keratinocytes and immune cells in inflammatory skin diseases

2021 ◽  
pp. 418-431
Author(s):  
Xinhui Ni ◽  
Yuping Lai
Keyword(s):  
Immune Cells ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Cell Type ◽  
Physical Barrier ◽  
Inflammatory Skin Diseases ◽  
Major Cell Type ◽  
Inflammatory Skin ◽  
Different Cell Types

Cutaneous homeostasis is maintained by dynamic cellular communications between different cell types in the skin through interactions with various mediators, including cytokines, chemokines and antimicrobial peptides/proteins (AMPs). Keratinocytes, as the major cell type of the epidermis, not only form a passive physical barrier, but also actively participate in the pathogenesis of many, if not all, inflammatory skin diseases. Keratinocytes highly interact with immune cells to shape, amplify or regulate inflammatory responses, thus triggering and/or sustaining these inflammatory skin diseases. In this review, crosstalk between keratinocytes and immune cells is summarized, and its contributions to two major inflammatory skin disorders including psoriasis and atopic dermatitis are highlighted.

scholarly journals Positive Influence of Probiotics on the Gut-Skin Axis

2020 ◽  
Vol 1 (1) ◽  
pp. 25-26
Author(s):  
Michael Sticherling
Keyword(s):  
Skin Diseases ◽  
Therapeutic Potential ◽  
Acne Vulgaris ◽  
Skin Inflammation ◽  
Skin Condition ◽  
Positive Influence ◽  
Inflammatory Skin Diseases ◽  
Synthetic Drugs ◽  
Inflammatory Skin ◽  
Diseased State

The existence of a gut-skin axis is supported by increasing evidence, but its translational potential is not widely recognized. Studies linked inflammatory skin diseases to an imbalanced gut microbiome; hence, the modulation of the gut microbiota to improve skin condition seems to be a feasible approach. Today, there is a growing interest in natural products as alternatives to synthetic drugs. In this respect, oral probiotics could be a simple, safe and cheap modality in the therapeutic management of skin inflammation. Unfortunately, very few studies have looked into how probiotic supplementation influences inflammatory skin disorders. The results, though promising, are difficult to implement in clinical practice due to the heterogeneity of the applied supplemental regimen in the different studies. In this Viewpoint, we aim to encourage the conduction of more research in that direction to explore unambiguously the therapeutic potential of oral probiotics in dermatology. We focus on the most common inflammatory skin diseases (atopic dermatitis, psoriasis, rosacea, acne vulgaris) with an associated gut dysbiosis, but we also discuss some less common, but very serious skin pathologies (eg erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa) that are possibly linked to a disturbed gut flora composition. We dissect the possible mechanisms along the gut-skin axis and highlight novel points where probiotics could interfere in this communication in the diseased state.

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