A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology. 

Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine

In the last few decades, the practical use of stem cells (SCs) in the clinic has attracted significant attention in the regenerative medicine due to the ability of these cells to proliferate and differentiate into other cell types. However, recent findings have demonstrated that the therapeutic capacity of SCs may also be mediated by their ability to secrete biologically active factors, including extracellular vesicles (EVs). Such submicron circular membrane-enveloped vesicles may be released from the cell surface and harbour bioactive cargo in the form of proteins, lipids, mRNA, miRNA, and other regulatory factors. Notably, growing evidence has indicated that EVs may transfer their bioactive content into recipient cells and greatly modulate their functional fate. Thus, they have been recently envisioned as a new class of paracrine factors in cell-to-cell communication. Importantly, EVs may modulate the activity of immune system, playing an important role in the regulation of inflammation, exhibiting broad spectrum of the immunomodulatory activity that promotes the transition from pro-inflammatory to pro-regenerative environment in the site of tissue injury. Consequently, growing interest is placed on attempts to utilize EVs in clinical applications of inflammatory-related dysfunctions as potential next-generation therapeutic factors, alternative to cell-based approaches. In this review we will discuss the current knowledge on the biological properties of SC-derived EVs, with special focus on their role in the regulation of inflammatory response. We will also address recent findings on the immunomodulatory and pro-regenerative activity of EVs in several disease models, including in vitro and in vivo preclinical, as well as clinical studies. Finally, we will highlight the current perspectives and future challenges of emerging EV-based therapeutic strategies of inflammation-related diseases treatment.

/pdf/stem-cell-derived-extracellular-vesicles-as-new-tools-in-qacdu6kg.pdf

Stem cell- derived extracellular vesicles as new tools in regenerative medicine - Immunomodulatory role and future perspectives

Exosomes from adipose-derived stem cells inhibit inflammation and oxidative stress in LPS-acute kidney injury.

Abstract Mesenchymal stem/stromal cells (MSCs)‐based therapy brings the reassuring capability to regenerative medicine through their self‐renewal and multilineage potency. Also, they secret a diversity of mediators, which are complicated in moderation of deregulated immune responses, and yielding angiogenesis in vivo. Nonetheless, MSCs may lose biological performance after procurement and prolonged expansion in vitro. Also, following transplantation and migration to target tissue, they encounter a harsh milieu accompanied by death signals because of the lack of proper tensegrity structure between the cells and matrix. Accordingly, pre-conditioning of MSCs is strongly suggested to upgrade their performances in vivo, leading to more favored transplantation efficacy in regenerative medicine. Indeed, MSCs ex vivo pre-conditioning by hypoxia, inflammatory stimulus, or other factors/conditions may stimulate their survival, proliferation, migration, exosome secretion, and pro-angiogenic and anti-inflammatory characteristics in vivo. In this review, we deliver an overview of the pre-conditioning methods that are considered a strategy for improving the therapeutic efficacy of MSCs in organ failures, in particular, renal, heart, lung, and liver. 

/pdf/recent-advances-in-pre-conditioned-mesenchymal-stem-stromal-hm1e8enw.pdf

Recent advances in pre-conditioned mesenchymal stem/stromal cell (MSCs) therapy in organ failure; a comprehensive review of preclinical studies

Mesenchymal Stem Cell Therapy in Kidney Diseases: Potential and Challenges

Abstract Background Ischemia–reperfusion injury (IRI)-induced acute kidney injury (AKI) can repair itself completely. However, most moderate and severe patients undergoing IRI-AKI progress to chronic kidney disease due to incomplete repair. The present study is aimed to investigate the role of bone marrow mesenchymal stem cell-derived exosomes (MSC-Exo) with indoleamine 2,3-dioxygenase (IDO) overexpression on incomplete repair in mice after IRI. Methods IRI mice was established by clamping the unilateral renal pedicles and challenged with MSC-Exo. Blood biochemical indexes and inflammation factors contents were measured by ELISA assay. Histopathological examinations were monitored by HE, Masson, Immunohistochemical and TUNEL staining. Immunofluorescence, flow cytometry and immunoblotting were used to detect the polarization of macrophages, respectively. Results As compared to sham operation mice, IRI mice showed high contents of serum BUN and Scr, and more severe damaged kidney tissues on days 1 and 3, which all gradually declined over time, showing the lowest level on day 7 after injury. Once treated with MSCs-Exo that could directly transfer to kidney tubular cells, the restoration of kidney functions significantly accelerated by contrast to IRI mice, and the promotive effects were more obvious in IDO-overexpressed MSCs-Exo (MSCs-Exo-IDO)-treated IRI mice. Furthermore, MSCs-Exo-IDO administration also accelerated renal tubular cells proliferation, restrained tubular cells apoptosis, fibrosis and inflammation factor secretions during self-repair process compared to IRI mice, whose effects were higher than MSCs-Exo-NC-challenged IRI mice and IDO overexpressing plasmid-injected IRI mice. Mechanistically, MSCs-Exo-NC and MSCs-Exo-IDO exposure promoted the polarization from M1 macrophage to M2 macrophage, leading to more anti-inflammatory factors production, and subsequently altered the inflammatory microenvironment of renal tubular cells, which facilitated the self-repair process in mice after IRI. Conclusion MSCs-derived exosome accelerated renal self-repair in IRI mice by activating M2 macrophages polarization, which effects were amplified by IDO overexpression in MSCs. Potentially, genetically modified MSCs-Exo is an effective approach to improve renal self-repair in IRI-AKI mice. 

/pdf/exosome-from-indoleamine-23-dioxygenase-overexpressing-bone-3pntax52.pdf

Exosome from indoleamine 2,3-dioxygenase-overexpressing bone marrow mesenchymal stem cells accelerates repair process of ischemia/reperfusion-induced acute kidney injury by regulating macrophages polarization

/pdf/exosome-from-indoleamine-23-dioxygenase-overexpressing-bone-29l6tvfb.pdf

Soy protein isolate (SPI) was used to prepare gels through probiotic fermentation. The effects of fermentation time (0–20 h) on the physicochemical properties of resulting gel were evaluated. The effect of probiotic fermentation on physicochemical properties of gel was found to highly depend on the fermentation time. The probiotic fermentation decreased the pH value below pH 4.75 and this process also induced SPI to form a gel upon 10 h. The formation of gel was indicated by the increase of particle size, viscosity and storage modulus, and appearance of a new peak in molecular weight distribution. The formation of porous and gel-like microstructure, due to the aggregation of SPI molecules, also occurred after 10 h of fermentation. Water holding capacity of SPI-based gel reached the highest value at 15 h fermentation and decreased with further fermentation. The probiotic fermentation caused an increase of band intensity of amide-A in FTIR spectra. It also caused a decrease of surface hydrophobicity and fluorescence intensity in intrinsic tryptophan fluorescence spectra. The subunits of SPI remained intact and were not affected by probiotic fermentation. 

Physicochemical properties of soybean protein isolate-based gel produced through probiotic fermentation

Abstract Dihydroartemisinin (DHA) has been found to inhibit the expression of von Willebrand factor (VWF), a marker of endothelial cell injury, but its mechanism in cerebral ischemia/reperfusion (I/R) injury remains obscure. In this study, I/R model was constructed through middle cerebral artery occlusion (MCAO) in rats, followed by DHA administration. The effect of DHA on rat cerebral I/R injury was investigated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, TUNEL staining, and Western blot. Brain microvascular endothelial cells (BMVECs) isolated from newborn rats were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R), and then treated with DHA. The results showed that MCAO treatment induced infarction, nerve cell apoptosis, and brain tissue impairment in rats, which was mitigated by DHA. OGD/R inhibited viability and accelerated apoptosis of BMVECs, which was alleviated by DHA. I/R procedures or OGD/R up-regulated expressions of VWF, ATG7, Beclin1, and LC3-II/LC3-I ratio, while down-regulating Occludin, Claudin-5, ZO-1, P62, SIRT1, and FOXO1 expressions in vivo and in vitro; however, these effects of I/R procedures or OGD/R were offset by DHA. VWF overexpression reversed the above effects of DHA on OGD/R-induced BMVECs. In summary, DHA ameliorates cerebral I/R injury in rats by reducing VWF level and activating autophagy-mediated SIRT1/FOXO1 signaling pathway.

/pdf/dihydroartemisinin-ameliorates-cerebral-i-r-injury-in-rats-1nbq75fz.pdf

Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway

Sirtuin 1 （SIRT1）, a member of the conserved sirtuin family, is a nicotinamide adenine dinucleotide （NAD）-dependent histone and nonhistone deacetylase, participating in the regulation of longevity, energy metabolism, stress, inflammation, tumor, and so on. In recent years, some scholars have found that SIRT1 can protect subepithelial collagen and prevent ultraviolet irradiation-induced photoaging, and also play an important anti-inflammatory effect via down-regulating cytokines such as STAT3 and COX2. The relationship between SIRT1 and skin tumors is complex, and SIRT1 may act as either an oncogene or a tumor- suppressor gene. SIRT1 activators and inhibitors may play an important role in the treatment and prevention of skin diseases in future.

Key words: 
Sirtuins;  Light;  Cell aging;  Skin neoplasms

Sirtuin 1 in skin diseases

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Exosome from indoleamine 2,3-dioxygenase-overexpressing bone marrow mesenchymal stem cells accelerates repair process of ischemia/reperfusion-induced acute kidney injury by regulating macrophages polarization

Exosome from indoleamine 2,3-dioxygenase-overexpressing bone marrow mesenchymal stem cells accelerates repair process of ischemia/reperfusion-induced acute kidney injury by regulating macrophages polarization

Physicochemical properties of soybean protein isolate-based gel produced through probiotic fermentation

Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway

Sirtuin 1 in skin diseases