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the effect of collagen and fibrin hydrogels encapsulated with adipose tissue mesenchymal stem cell-derived exosomes for treatment of spinal cord injury in a rat model

background: mesenchymal stem cell (msc) derived exosomes (msc-de) have been demonstrated to be potential candidates for the treatment of rat spinal cord injury (sci).objective: the effect of ad-msc and ad-msc-de encapsulated into collagen and fibrin hydrogels on the treatment of sci in a rat animal model was investigated for introducing a new effective sci treatment methodmaterials and methods: the ad-msc-de was isolated using ultra-centrifugation at 100,000×g for 120 min and characterized by different methods. fibrin and collagen hydrogels were synthesized and then mixed with ad-msc-de suspension. the characterized ad-msc-de were encapsulated into collagen and fibrin hydrogels. eighteen adult male wister rats were randomly classified into 3 equal groups (n=6): the control group (sci rat without treatment), sci rat treated with either ad-msc-de encapsulated in collagen hydrogel or encapsulated in fibrin hydrogel groups. the treatment approaches were evaluated using clinical, histological, and molecular assays.results: the ad-msc-de encapsulated into fibrin and collagen groups showed better clinical function than the control group. the ad-msc-de encapsulated into fibrin and collagen also improved sci-induced polio and leuko-myelomalacia and leads to higher expression of nf protein than the control group. in the ad-msc-de encapsulated into collagen and fibrin leads to up-regulation the mean levels of nefl (23.82 and 24.33, respectively), enos (24.31 and 24.53, respectively), and ck19 mrnas (24.23 and 23.98, respectively) compared to the control group.conclusion: the ad-msc-de encapsulated within ecm-based hydrogel scaffolds such as collagen and fibrin can regenerate the injured nerve in sci rats and reduce spinal cord lesion-induced central neuropathic pain.

frontiers | the role of natural exosomes from shed-msc in immunoregulation of m0/m1 polarized macrophage cells

introductionexosomes (exos) as a targeted cell-free therapy could offer a new therapeutic strategy for immune-mediated inflammatory diseases, due to their st...

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perspective chapter: development of exosomes for esthetic use

while there are thousands of peer-reviewed papers on exosomes, most of the work has been done in the medical field. studies and clinical trials on exosome-related products for the esthetic industry have just begun to be a regular occurrence. one of the reasons for this is a lack of regulatory approval for any exosome use. the fda does not regulate topical cosmetic use, while only a few exosomes are registered on the international cosmetic ingredient dictionary (icid) of the personal care product council (pcpc), so most esthetic providers are utilizing exosomes in this manner. clinical uses for exosomes in esthetic practice include the treatment of burns, active acne, atopic dermatitis, and chronic skin irritations. when used in combination with energy-based device treatment, exosomes reduce inflammation and redness, improve the rapidity of healing for laser and microneedling patients, and reduce the tendency for fibrosis and thick hypertrophic scar formation when used topically. byong cho is the ceo & cto of exocobio, one of the four largest exosome companies globally. he has developed a large research, development, and gmp manufacturing facility just south of seoul, korea. his topic, the development of exosomes for clinical esthetic use, will take us through the process of developing a safe and cost-effective biological regenerative product while staying in line with regulatory limitations.

mesenchymal stem cell-derived exosome and liposome hybrids as transfection nanocarriers of cas9-gfp plasmid to hek293t cells

exosomes are natural membrane-enclosed nanovesicles (30–150 nm) involved in cell-cell communication. recently, they have garnered considerable interest as nanocarriers for the controlled transfer of therapeutic agents to cells. here, exosomes were derived from bone marrow mesenchymal stem cells using three different isolation methods. relative to filtration and spin column condensation, the size exclusion chromatography led to the isolation of exosomes with the highest purity. these exosomes were then hybridized with liposomes using freeze-thaw cycles and direct mixing techniques to evaluate whether this combination enhances the transfection efficiency of large plasmids. the efficiency of these hybrids in transferring the cas9-green fluorescent protein plasmid (pcas9-gfp) into the human embryonic kidney 293t (hek293t) cells was evaluated compared to the pure exosomes. both cas9-gfp-loaded exosomes and exosome-liposome hybrids were taken up well by the hek293t cells and were able to transfect them with their plasmid loads. meanwhile, the treatment of the cells with plasmids alone, without any vesicles, resulted in no transfection, indicating that the exosome and exosome-liposome hybrids are essential for the transfer of the plasmids across the cell membrane. the pure exosomes and the hybrids incorporating liposomes obtained by the heating method transfected the cells more efficiently than those containing liposomes obtained by the thin film hydration technique. interestingly, the method of combining exosomes with liposomes (freeze-thaw vs. direct mixing) proved to be more decisive in determining the size of the vesicular hybrid than their composition. in contrast, the liposome component in the hybrids proved to be decisive for determining the transfection efficiency.

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cml derived exosomes promote tumor favorable functional performance in t cells - bmc cancer

background leukemic cells facilitate the creation of the tumor-favorable microenvironment in the bone marrow niche using their secreted factors. there are not comprehensive details about immunosuppressive properties of chronic myelogenous leukemia-derived exosomes in the bone marrow stromal and immune compartment. we explained here that k562-derived exosomes could affect the gene expression, cytokine secretion, nitric oxide (no) production, and redox potential of human primary cord blood-derived t cells (cb t cells). methods human primary cord blood-derived t cells were treated with k562-derived exosomes. we evaluated the expression variation of some critical genes activated in suppressor t cells. the alterations of some inflammatory and anti-inflammatory cytokines levels were assessed using elisa assay and real-time pcr. finally, no production and intracellular ros level in cb t cells were evaluated using greiss assay and flow cytometry, respectively. results our results showed the over-expression of the genes involved in inhibitory t cells, including nqo1, pd1, and foxp3. in contrast, genes involved in t cell activation such as cd3d and nfatc3 have been reduced significantly. also, the expression of interleukin 10 (il-10) and interleukin 6 (il-6) mrnas were significantly up-regulated in these cells upon exosome treatment. in addition, secretion of the interleukin 10, interleukin 6, and interleukin 17 (il-17) proteins increased in t cells exposed to k562-derived exosomes. finally, k562-derived exosomes induce significant changes in the no production and intracellular ros levels in cb t cells. conclusions these results demonstrate that k562-derived exosomes stimulate the immunosuppressive properties in cb-derived t cells by inducing anti-inflammatory cytokines such as il-10, reducting ros levels, and arising of no synthesis in these cells. moreover, considering the elevation of foxp3, il-6, and il-17 levels in these cells, exosomes secreted by cml cells may induce the fates of t cells toward tumor favorable t cells instead of conventional activated t cells.

potential of exosomes as cell-free therapy | ijn

potential of exosomes as cell-free therapy in articular cartilage regeneration

establishing a working range for effective msc-ev dose

extracellular vesicles / exosomes derived from mscs are promising therapeutic candidates that have been used in several clinical trials.

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home | harmony medical aesthetics

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exosomes derived from bone marrow dendritic cells exhibit protective and therapeutic potential against chemically induced chronic pancreatitis in rats - inflammation

background chronic pancreatitis (cp) is a specific clinical disorder that develops from pancreatic fibrosis and immune cell dysregulation. it has been proposed that bone marrow dendritic cells (bmdcs) exosomes have significant effects on immune regulation. thus, the current study acquainted the prophylactic and therapeutic effects of exosomes derived from bmdcs on a rat model of cp. materials and methods bmdcs were prepared and identified, and then the exosomes were isolated by differential ultracentrifugation. prophylactic and therapeutic effects of exosomes were investigated on l-arginine induced cp model. results administration of two tail vein injections of exosomes (200 μg/kg/dose suspended in 0.2 ml pbs) markedly improved the pancreatic function and histology compared to cp group. moreover, exosomes prominently mitigated the increase in amylase, lipase, tumor necrosis factor-α (tnf-α), transforming growth factor-β (tgf-β) and elevated antioxidant enzymes; catalase, superoxide dismutase (sod) and glutathione peroxidase (gpx). conclusion bmdcs exosomes can be considered as a promising candidate, with a high efficacy and stability compared with its parent cell, for management of cp and similar inflammatory diseases.

impact of exosome therapy on pancreatic cancer and its progression - medical oncology

pancreatic cancer, one of the most aggressive tumors, has a dismal prognosis because of the low rates of early identification, fast progression, difficulties following surgery, and the ineffectiveness of current oncologic therapies. there are no imaging techniques or biomarkers that can accurately identify, categorize, or predict the biological behavior of this tumor. exosomes are extracellular vesicles that play a crucial rule in the progression, metastasis, and chemoresistance of pancreatic cancer. they have been verified to be potential biomarkers for pancreatic cancer management. studying the role of exosomes in pancreatic cancer is substantial. exosomes are secreted by most eukaryotic cells and participated in intercellular communication. the components of exosomes, including proteins, dna, mrna, microrna, long non-coding rna, circular rna, etc., play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. hereby, in this concise review, we intend to summarize exosomes components and isolation, exosome secretion, function, importance of exosomes in the progression of pancreatic cancer and exosomal mirnas as possible pancreatic cancer biomarkers. finally, the application potential of exosomes in the treatment of pancreatic cancer, which provides theoretical supports for using exosomes to serve precise tumor treatment in the clinic, will be discussed.

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human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes - scientific reports

alzheimer's disease (ad) is characterized by the accumulation of β-amyloid peptide (aβ) in the brain because of an imbalance between aβ production and clearance. neprilysin (nep) is the most important aβ-degrading enzyme in the brain. thus, researchers have explored virus-mediated nep gene delivery. however, such strategies may entail unexpected risks and thus exploration of a new possibility for nep delivery is also required. here, we show that human adipose tissue-derived mesenchymal stem cells (adscs) secrete exosomes carrying enzymatically active nep. the nep-specific activity level of 1 μg protein from adsc-derived exosomes was equivalent to that of ~ 0.3 ng of recombinant human nep. of note, adsc-derived exosomes were transferred into n2a cells and were suggested to decrease both secreted and intracellular aβ levels in the n2a cells. importantly, these characteristics were more pronounced in adscs than bone marrow-derived mesenchymal stem cells, suggesting the therapeutic relevance of adsc-derived exosomes for ad.

comparison between stem cell therapy and stem cell derived exosomes on induced multiple sclerosis in dogs - bmc veterinary research

background multiple sclerosis (ms) is a chronic condition that primarily manifests as demyelination of neuronal axons in the central nervous system, due to the loss or attack of oligodendroglia cells that form myelin. stem cell therapy has shown promising results for the treatment of ms due to its capability to halt the immune attack, stop apoptosis and axonal degeneration, and differentiate into oligodendrocytes. stem cell-derived exosomes (exosomes) have shown great capabilities for neuronal diseases as they have growth factors, complex sets of mirna, enzymes, proteins, major peptides, lipids, and macromolecules with anti-inflammatory, angiogenesis, and neurogenesis activities. methods this study aimed to compare the healing properties of stem cells, against exosomes for the treatment of an experimentally induced ms dog model. dog models of ms received either a single treatment of stem cells or a single treatment of exosomes intrathecally and the treatment process was evaluated clinically, radiologically, histopathologically, and electron microscopy and cerebrospinal fluid analysis. results showed marked amelioration of the clinical signs in both treated groups compared to the control one, magnetic resonance scans showed the resolution of the hyperintense lesions at the end of the study period, the histopathology and electron microscopy showed marked healing properties and remyelination in treated groups with superiority of the stem cells compared to exosomes. conclusions although stem cell results were superior to exosomes therapy; exosomes have proven to be effective and safe important actors in myelin regeneration, and their use in diseases like ms helps to stimulate remyelination.

the efficacy of exosomes from human chemically derived hepatic progenitors in liver damage alleviation: a preclinical experimental study

kim m, et al. ann surg treat res. 2024 nov;107(5):252-263. https://doi.org/10.4174/astr.2024.107.5.252

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anticarcinogenic impact of extracellular vesicles (exosomes) from cord blood stem cells in malignant melanoma: a potential biological treatment - pubmed

incidence of malignant melanoma has become the 5th in the uk. to date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology-based strategies. recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits …

residual matrix from different separation techniques impacts exosome biological activity - scientific reports

exosomes are gaining a prominent role in research due to their intriguing biology and several therapeutic opportunities. however, their accurate purification from body fluids and detailed physicochemical characterization remain open issues. we isolated exosomes from serum of patients with multiple myeloma by four of the most popular purification methods and assessed the presence of residual contaminants in the preparations through an ad hoc combination of biochemical and biophysical techniques - including western blot, colloidal nanoplasmonics, atomic force microscopy (afm) and scanning helium ion microscopy (him). the preparations obtained by iodixanol and sucrose gradients were highly pure. to the contrary, those achieved with limited processing (serial centrifugation or one step precipitation kit) resulted contaminated by a residual matrix, embedding the exosomes. the contaminated preparations showed lower ability to induce nfkb nuclear translocation in endothelial cells with respect to the pure ones, probably because the matrix prevents the interaction and fusion of the exosomes with the cell membrane. these findings suggest that exosome preparation purity must be carefully assessed since it may interfere with exosome biological activity. contaminants can be reliably probed only by an integrated characterization approach aimed at both the molecular and the colloidal length scales.

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