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 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 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.

Therapeutic Potential of Endothelial Colony Forming Cells Derived from Human Umbilical Cord Blood

2019 ◽  
Vol 14 (6) ◽  
pp. 460-465 ◽  
Author(s):  
Jing Jia ◽  
Baitao Ma ◽  
Shaoshuai Wang ◽  
Ling Feng
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Tissue Regeneration ◽  
Umbilical Cord Blood ◽  
Therapeutic Potential ◽  
Human Umbilical Cord Blood ◽  
Proliferative Potential ◽  
Human Umbilical Cord ◽  
Preclinical Studies ◽  
Endothelial Colony Forming Cells

Endothelial progenitor cells (EPCs) are implicated in multiple biologic processes such as vascular homeostasis, neovascularization and tissue regeneration, and tumor angiogenesis. A subtype of EPCs is referred to as endothelial colony-forming cells (ECFCs), which display robust clonal proliferative potential and can form durable and functional blood vessels in animal models. In this review, we provide a brief overview of EPCs’ characteristics, classification and origins, a summary of the progress in preclinical studies with regard to the therapeutic potential of human umbilical cord blood derived ECFCs (CB-ECFCs) for ischemia repair, tissue engineering and tumor, and highlight the necessity to select high proliferative CB-ECFCs and to optimize their recovery and expansion conditions.

scholarly journals Soft Tissue Repair with Easy-Accessible Autologous Newborn Placenta or Umbilical Cord Blood in Severe Malformations: A Primary Evaluation

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Åsa Ekblad ◽  
Magdalena Fossum ◽  
Cecilia Götherström
Keyword(s):  
Soft Tissue ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Donor Site ◽  
Autologous Transplantation ◽  
Donor Site Morbidity ◽  
Primary Evaluation

Disrupted organogenesis leads to permanent malformations that may require surgical correction. Autologous tissue grafts may be needed in severe lack of orthotopic tissue but include donor site morbidity. The placenta is commonly discarded after birth and has a therapeutic potential. The aim of this study was to determine if the amnion from placenta or plasma rich of growth factors (PRGF) with mononuclear cells (MNC) from umbilical cord blood (UCB), collected noninvasively, could be used as bio-constructs for autologous transplantation as an easy-accessible no cell culture-required method. Human amnion and PRGF gel were isolated and kept in culture for up to 21 days with or without small intestine submucosa (SIS). The cells in the constructs showed a robust phenotype without induced increased proliferation (Ki67) or apoptosis (caspase 3), but the constructs showed decreased integrity of the amnion-epithelial layer at the end of culture. Amnion-residing cells in the SIS constructs expressed CD73 or pan-cytokeratin, and cells in the PRGF-SIS constructs expressed CD45 and CD34. This study shows that amnion and UCB are potential sources for production of autologous grafts in the correction of congenital soft tissue defects. The constructs can be made promptly after birth with minimal handling or cell expansion needed.

scholarly journals The Effect of Platelets on Thrombin Generation in Cord Blood and Peripheral Neonatal Blood in the Premature Infant; The Event Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3188-3188
Author(s):  
Claire Anne Murphy ◽  
Elaine Neary ◽  
Barry Kevane ◽  
Daniel O'Reilly ◽  
John O'Loughlin ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Umbilical Cord Blood ◽  
Research Funding ◽  
Thrombin Generation ◽  
Phospholipid Content ◽  
Term Infants ◽  
Time To Peak ◽  
Neonatal Blood

Abstract Introduction Infants born very preterm (<32 weeks) are at increased risk of haemorrhage, particularly intraventricular haemorrhage which can result in short and long term morbidity. Routine clinical laboratory tests such as the prothrombin time and activated partial thromboplastin time are frequently abnormal in this patient group but do not appear to correlate with clinical outcomes. Moreover, while reduced levels of circulating coagulation factors and platelet hypo-reactivity have been reported, plasma thrombin generation (TG), has been reported to be similar or even enhanced in very preterm infants when compared to term infants. Extracellular vesicles, comprising of lipid-bound nanoparticles released from cells (including platelets), may potentially play a role in modulating neonatal haemostasis. We aimed to characterize phospholipid (PL)-dependent plasma thrombin generation in platelet-rich (PRP) and platelet-poor plasma (PPP) in premature infants in both umbilical cord blood & peripheral neonatal blood using calibrated automated thrombography (CAT). Methods In this prospective observational study, PRP and PPP was prepared by centrifugation from citrated umbilical cord blood and peripheral neonatal blood collected from premature infants (24 - 31 weeks) and healthy term controls (>37 weeks). No samples were collected from heparinised lines. Parameters of plasma thrombin generation in PRP were assessed using CAT, with thrombin generation stimulated by tissue factor only (TF; final concentration 1pM). CAT was also repeated in PPP using only TF and no exogenous PL (rendering the assay dependent upon the endogenous PL content of plasma). Results In the analysis of umbilical cord blood PRP, plasma thrombin generation was accelerated in the preterm infant group with a significantly shorter time to peak TG observed. The other parameters of TG were similar in both groups (Table 1). In the subset of infants from whom peripheral blood samples were available, there was further evidence of enhanced plasma TG in preterm PRP relative to term infants (Table 2). In this subgroup, the lag time and time to peak thrombin were significantly shorter in the preterm group and peak thrombin was significantly higher. TG was also assessed in both PPP and PRP prepared from umbilical cord blood samples in a subgroup of infants (n=10 term, n=6 preterm) using 1pM TF only, rendering the assay dependent on the phospholipid content of plasma. No difference was observed in any CAT parameters, suggesting that neonatal PPP phospholipid content (potentially from circulating extracellular vesicles) is sufficient to support thrombin generation in the absence of exogenous phospholipid. Conclusion These preliminary data suggest that neonatal PRP, measured in both umbilical cord blood and peripheral neonatal blood, has similar thrombin generation or may even be hypercoagulable, compared with healthy term controls. Moreover, neonatal plasma phospholipid appears to support thrombin generation in the absence of exogenous phospholipid. This ongoing prospective study aims to further characterize the platelet-dependency of neonatal thrombin generation and evaluate the potential role of extracellular vesicles in neonatal haemostasis. Figure 1 Figure 1. Disclosures Maguire: Actelion: Research Funding; Bayer Pharma: Research Funding. Ni Ainle: Leo Pharma: Research Funding; Actelion: Research Funding; Daiichi-Sankyo: Research Funding; Bayer Pharma: Research Funding.

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