CAR-T cell-derived exosomes: a new perspective for cancer therapy.

Chimeric antigen receptor (CAR)-T cell adoptive immunotherapy is a promising cancer treatment that uses genetically engineered T cells to attack tumors. However, this therapy can have some adverse effects. CAR-T cell-derived exosomes are a potential alternative to CAR-T cells that may overcome some limitations. Exosomes are small vesicles released by cells and can carry a variety of molecules, including proteins, RNA, and DNA. They play an important role in intercellular communication and can be used to deliver therapeutic agents to cancer cells. The application of CAR-T cell-derived exosomes could make CAR-T cell therapy more clinically controllable and effective. Exosomes are cell-free, which means that they are less likely to cause adverse reactions than CAR-T cells. The combination of CAR-T cells and exosomes may be a more effective way to treat cancer than either therapy alone. Exosomes can deliver therapeutic agents to cancer cells where CAR-T cells cannot reach. The appropriate application of both cellular and exosomal platforms could make CAR-T cell therapy a more practicable treatment for cancer. This combination therapy could offer a safe and effective way to treat a variety of cancers.

Topical ophthalmic instillation of engineered hMSCs-derived exosomes: A novel non-invasive therapeutic strategy for ocular posterior-segment disorder.

Due to the presence of protective mechanisms and blood-ocular barriers in the eye, drugs aimed at treating posterior segment ophthalmic disorder have to be administrated mostly through periocular or intravitreal injection. In the current study, we sought to investigate whether topical ophthalmic instillation of human mesenchymal stem cells (hMSCs)-derived exosomes can prevent and treat experimental autoimmune uveitis (EAU), a posterior segment ophthalmic disease induced in animals and considered a model of human autoimmune diseases of the eye. Our studies reveal that topical ophthalmic instillation of hMSCs-derived exosomes can effectively ameliorate EAU. More importantly, we demonstrate that exosomes modified by trans-activator of transcription peptide (TAT) were more effective than naive exosomes in penetrating ocular barrier and preventing/treating EAU. Taken together, these results indicate that topical ophthalmic instillation of TAT-peptide modified exosomes represents a novel non-invasive therapeutic strategy for posterior-segment ophthalmic disorders.

Progress of mesenchymal stem cells (MSCs) & MSC-Exosomes combined with drugs intervention in liver fibrosis.

Liver fibrosis is an intrahepatic chronic damage repair response caused by various reasons such as alcoholic liver, fatty liver, viral hepatitis, autoimmune diseases, etc., and is closely related to the progression of liver disease. Currently, the mechanisms of liver fibrosis and its treatment are hot research topics in the field of liver disease remedy. Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential, which can ameliorate fibrosis through hepatic-directed differentiation, paracrine effects, and immunomodulation. However, the low inner-liver colonization rate, low survival rate, and short duration of intervention after stem cell transplantation have limited their wide clinical application. With the intensive research on liver fibrosis worldwide, it has been found that MSCs and MSCs-derived exosomes combined with drugs have shown better intervention efficiency than utilization of MSCs alone in many animal models of liver fibrosis. In this paper, we review the interventional effects and mechanisms of mesenchymal stem cells and their exosomes combined with drugs to alleviate hepatic fibrosis in vivo in animal models in recent years, which will provide new ideas to improve the efficacy of mesenchymal stem cells and their exosomes in treating hepatic fibrosis in the clinic.

Stem cell and exosome therapies for regenerating damaged myocardium in heart failure.

Finding novel treatments for cardiovascular diseases (CVDs) is a hot topic in medicine; cell-based therapies have reported promising news for controlling dangerous complications of heart disease such as myocardial infarction (MI) and heart failure (HF). Various progenitor/stem cells were tested in various in-vivo, in-vitro, and clinical studies for regeneration or repairing the injured tissue in the myocardial to accelerate the healing. Fetal, adult, embryonic, and induced pluripotent stem cells (iPSC) have revealed the proper potency for cardiac tissue repair. As an essential communicator among cells, exosomes with specific contacts (proteins, lncRNAs, and miRNAs) greatly promote cardiac rehabilitation. Interestingly, stem cell-derived exosomes have more efficiency than stem cell transplantation. Therefore, stem cells induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), cardiac stem cells (CDC), and skeletal myoblasts) and their-derived exosomes will probably be considered an alternative therapy for CVDs remedy. In addition, stem cell-derived exosomes have been used in the diagnosis/prognosis of heart diseases. In this review, we explained the advances of stem cells/exosome-based treatment, their beneficial effects, and underlying mechanisms, which will present new insights in the clinical field in the future.

Exosomes Derived from Adipose Mesenchymal Stem Cells Promote Regeneration of Injured Liver in Minipigs.

Hepatic ischemia/reperfusion injury (IRI) is an important factor affecting liver regeneration and functional recovery postoperatively. Many studies have suggested that mesenchymal stem cells (MSCs) contribute to hepatic tissue repair and functional recovery through paracrine mechanisms mediated by exosomes. Minipigs exhibit much more similar characteristics of the liver to those of humans than rodents. This study aimed to explore whether exosomes from adipose-derived MSCs (ADSCs-exo) could actively promote liver regeneration after hepatectomy combined with HIRI in minipigs and the role they play in the cell proliferation process. This study also compared the effects and differences in the role of ADSCs and ADSCs-exo in the inflammatory response and liver regeneration. The results showed that ADSCs-exo suppressed histopathological changes and reduced inflammatory infiltration in the liver; significantly decreased levels of ALT, TBIL, HA, and the pro-inflammatory cytokines TNF-α, IL-6, and CRP; increased levels of the anti-inflammatory cytokine IL-10 and the pro-regeneration factors Ki67, PCNA, CyclinD1, HGF, STAT3, VEGF, ANG1, ANG2; and decreased levels of the anti-regeneration factors SOCS3 and TGF-ß. These indicators above showed similar changes with the ADSCs intervention group. Indicating that ADSCs-exo can exert the same role as ADSCs in regulating inflammatory responses and promoting liver regeneration. Our findings provide experimental evidence for the possibility that ADSCs-exo could be considered a safe and effective cell-free therapy to promote regeneration of injured livers.

3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius.

Currently, the repair of large bone defects still faces numerous challenges, with the most crucial being the lack of large bone grafts with good osteogenic properties. In this study, a novel bone repair implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate a porous zinc scaffold, combining it under vacuum conditions with highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed the presence of tea saucer-shaped exosomes with a double-layered membrane structure, ranging in diameter from 30-150 nm, with an average size of 86.3 nm and a concentration of 3.28E+09 particles/mL. In vitro experiments demonstrated that the zinc scaffold displayed no significant cytotoxicity, and loading exosomes enhanced the zinc scaffold's ability to promote osteogenic cell activity while inhibiting osteoclast activity. In vivo experiments on rabbits indicated that the hepatic and renal toxicity of the zinc scaffold decreased over time, and the loading of exosomes alleviated the hepatic and renal toxic effects of the zinc scaffold. Throughout various stages of repairing radial bone defects in rabbits, loading exosomes reinforced the zinc scaffold's capacity to enhance osteogenic cell activity, suppress osteoclast activity, and promote angiogenesis. This effect may be attributed to BF Exo's regulation of p38/STAT1 signaling. This study signifies that the combined treatment of degradable porous zinc scaffolds and BF Exo is an effective and biocompatible strategy for bone defect repair therapy.

Exosomes Derived from Mesenchymal Stem Cells: Therapeutic Opportunities for Spinal Cord Injury.

Spinal cord injury (SCI) is a serious neurological condition comprising primary and secondary injury and causing severe neurological impairments. The effect of the conventional treatment is limited, including supportive therapy and emergency surgery. Exosomes derived from mesenchymal stem cells (MSCs-Exos) were previously reported to exert its potential therapeutic effects on SCI. Compared with mesenchymal stem cells (MSCs) transplantation for SCI, MSC-Exos showed several superiorities. In the present review, we summarized the revealed data of mechanisms underlying MSC-Exos repairing of SCI and discussed the issues of MSC-Exos use. Thus, in this review we summarized the latest studies on MSCs-Exos in the therapy of SCI and discussed whether MSCs-Exos can be applied to SCI and the prospects of transformation application.

Mesenchymal Stem Cell-Derived Exosomes as Drug Carriers for Delivering miRNA-29b to Ameliorate Inflammation in Corneal Injury Via Activating Autophagy.

Purpose: Corneal injury (CI) resulting in corneal opacity remains a clinical challenge. Exosomes (Exos) derived from bone marrow mesenchymal stem cells (BMSCs) have been proven effective in repairing various tissue injuries and are also considered excellent drug carriers due to their biological properties. Recently, microRNA-29b (miR-29b) was found to play an important role in the autophagy regulation which correlates with cell inflammation and fibrosis. However, the effects of miR-29b and autophagy on CI remain unclear. To find better treatments for CI, we used Exos to carry miR-29b and investigated its effects in the treatment of CI. Methods: BMSCs were transfected with miR-29b-3p agomir/antagomir and negative controls (NCs) to obtain Exos-29b-ago, Exos-29b-anta, and Exos-NC. C57BL/6J mice that underwent CI surgeries were treated with Exos-29b-ago, Exos-29b-anta, Exos-NC, or PBS. The autophagy, inflammation, and fibrosis of the cornea were estimated by slit-lamp, hematoxylin and eosin (H&E) staining, immunofluorescence, RT‒qPCR, and Western blot. The effects of miR-29b-3p on autophagy and inflammation in immortalized human corneal epithelial cells (iHCECs) were also investigated. Results: Compared to PBS, Exos-29b-ago, Exos-29b-anta, and Exos-NC all could ameliorate corneal inflammation and fibrosis. However, Exos-29b-ago, which accumulated a large amount of miR-29b-3p, exerted excellent potency via autophagy activation by inhibiting the PI3K/AKT/mTOR pathway and further inhibited corneal inflammation via the mTOR/NF-κB/IL-1ß pathway. After Exos-29b-ago treatment, the expressions of collagen type III, α-smooth muscle actin, fibronectin, and vimentin were significantly decreased than in other groups. In addition, overexpression of miR-29b-3p prevented iHCECs from autophagy impairment and inflammatory injury. Conclusions: Exos from BMSCs carrying miR-29b-3p can significantly improve the therapeutic effect on CI via activating autophagy and further inhibiting corneal inflammation and fibrosis.

Mesenchymal stem cells-derived exosomes alleviate temporomandibular joint disc degeneration in temporomandibular joint disorder.

Temporomandibular joint (TMJ) disorder (TMD) is a chronic progressive disease that is commonly seen in clinical settings. TMJ disc degeneration is an important manifestation of TMD, and further aggravates the progression of TMD. However, treatments on TMJ disc degeneration are very limited till now. In this study, we first observed the effects of bone marrow stem cells (BMSC) conditioned medium on functions of TMJ disc fibroblasts. Then BMSC-derived small extracellular vesicles (BMSC-EVs) were isolated and exposed to TMJ disc fibroblasts. RNA-sequencing was used to further investigate the mechanisms. BMSC-EVs were finally injected into a rat model with TMD. Results showed that in the transwell co-culture system, the medium derived from BMSC reduced inflammation and enhanced chondrogenesis in TMJ disc fibroblasts. BMSC-EVs promoted proliferation, migration, and chondrogenic differentiation of TMJ disc fibroblasts, and inhibited apoptosis and inflammatory responses. Local injection of BMSC-EVs into the TMD model alleviated TMJ disc degeneration. Therefore, BMSC-EVs were a potentially effective, sustainable and clinically translational-promising option for TMJ disc degeneration, and further reduce the progression of TMD.

Exosomes isolated from TNF-α-treated bone marrow mesenchymal stem cells ameliorate pelvic floor dysfunction in rats.

Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential therapeutical effects of exosomes derived from BMSCs treated with tumour necrosis factor (TNF)-α on the symptoms of PFD in rats are unknown. Exosomes extracted from BMSCs treated with or without TNF-α were applied to treat PFD rats. Our findings revealed a significant elevation in interleukin (IL)-6 and TNF-α, and matrix metalloproteinase-2 (MMP2) levels in the vaginal wall tissues of patients with pelvic organ prolapse (POP) compared with the control group. Daily administration of exosomes derived from BMSCs, treated either with or without TNF-α (referred to as Exo and TNF-Exo), resulted in increased void volume and bladder void pressure, along with reduced peak bladder pressure and leak point pressure in PFD rats. Notably, TNF-Exo treatment demonstrated superior efficacy in restoring void volume, bladder void pressure and the mentioned parameters compared with Exo treatment. Importantly, TNF-Exo exhibited greater potency than Exo in restoring the levels of multiple proteins (Elastin, Collagen I, Collagen III, IL-6, TNF-α and MMP2) in the anterior vaginal walls of PFD rats. The application of exosomes derived from TNF-α-treated BMSCs holds promise as a novel therapeutic approach for treating PFD.

Emerging Roles of Exosomes in Stroke Therapy.

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell-derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on (1) the therapeutic potential of exosomes in stroke treatment, (2) the optimization process of upstream and downstream production, and (3) preclinical application in a stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications.

Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.

Exosomes as a therapeutic tool to promote neurorestoration and cognitive function in neurological conditions: Achieve two ends with a single effort.

Exosomes possess a significant role in intercellular communications. In the nervous system, various neural cells release exosomes that not only own a role in intercellular communications but also eliminate the waste of cells, maintain the myelin sheath, facilitate neurogenesis, and specifically assist in normal cognitive function. In neurological conditions including Parkinson's disease (PD), Alzheimer's disease (AD), traumatic brain injury (TBI), and stroke, exosomal cargo like miRNAs take part in the sequela of conditions and serve as a diagnostic tool of neurological disorders, too. Exosomes are not only a diagnostic tool but also their inhibition or administration from various sources like mesenchymal stem cells and serum, which have shown a worthy potential to treat multiple neurological disorders. In addition to neurodegenerative manifestations, cognitive deficiencies are an integral part of neurological diseases, and applying exosomes in improving both aspects of these diseases has been promising. This review discusses the status of exosome therapy in improving neurorestorative and cognitive function following neurological disease.

Intranasal Administration of Umbilical Cord Mesenchymal Stem Cell Exosomes Alleviates Parkinson's Disease.

Parkinson's disease (PD) is a common and complex neurodegenerative disease. This disease is typically characterized by the formation of Lewy bodies in multiple brain regions and dopaminergic neuronal loss in the substantia nigra pars compacta, resulting in non-motor symptoms (e.g., olfactory deficits) and motor dysfunction in the late stages. There is yet no effective cure for Parkinson's disease. Considering the neuroprotective effects of exosomes, we investigated whether intranasal administration of umbilical cord mesenchymal stem cell exosomes could improve behavioral functions in PD mice. First, exosomes were endocytosed by the cells in vitro and in vivo, indicating that exosomes can cross the blood-brain barrier. Second, we found that both motor and non-motor functions of the PD models were effectively improved during intranasal exosomes treatment. Finally, the activity of olfactory bulb neurons was improved and the loss of dopaminergic neurons in the substantia nigra pars compacta was reversed. Moreover, exosomes attenuated microglia and astrocyte activation, leading to a low level of inflammation in the brain. In conclusion, our study provided a new reference for the clinical application of exosomes in the treatment of PD.

Advances in Exosome-Based Therapies for the Repair of Peripheral Nerve Injuries.

Peripheral nerve injuries (PNIs) are the term used to describe injuries that occur to the nerve fibers of the peripheral nervous system (PNS). Such injuries may be caused by trauma, infection, or aberrant immunological response. Although the peripheral nervous system has a limited capacity for self-repair, in cases of severe damage, this process is either interrupted entirely or is only partially completed. The evaluation of variables that promote the repair of peripheral nerves has consistently been a focal point. Exosomes are a subtype of extracellular vesicles that originate from cellular sources and possess abundant proteins, lipids, and nucleic acids, play a critical role in facilitating intercellular communication. Due to their modifiable composition, they possess exceptional capabilities as carriers for therapeutic compounds, including but not limited to mRNAs or microRNAs. Exosome-based therapies have gained significant attention in the treatment of several nervous system diseases due to their advantageous properties, such as low toxicity, high stability, and limited immune system activation. The objective of this review article is to provide an overview of exosome-based treatments that have been developed in recent years for a range of PNIs, including nerve trauma, diabetic neuropathy, amyotrophic lateral sclerosis (ALS), glaucoma, and Guillain-Barre syndrome (GBS). It was concluded that exosomes could provide favorable results in the improvement of peripheral PNIs by facilitating the transfer of regenerative factors. The development of bioengineered exosome therapy for PNIs should be given more attention to enhance the efficacy of exosome treatment for PNIs.

Mesenchymal stem cell-derived exosomes for management of prostate cancer: An updated view.

Prostate cancer represents the second most prevalent form of cancer found in males, and stands as the fifth primary contributor to cancer-induced mortality on a global scale. Research has shown that transplanted mesenchymal stem cells (MSCs) can migrate by homing to tumor sites in the body. In prostate cancer, researchers have explored the fact that MSC-based therapies (including genetically modified delivery vehicles or vectors) and MSC-derived exosomes are emerging as attractive options to improve the efficacy and safety of traditional cancer therapies. In addition, researchers have reported new insights into the application of extracellular vesicle (EV)-MSC therapy as a novel treatment option that could provide a more effective and targeted approach to prostate cancer treatment. Moreover, the new generation of exosomes, which contain biologically functional molecules as signal transducers between cells, can simultaneously deliver different therapeutic agents and induce an anti-tumor phenotype in immune cells and their recruitment to the tumor site. The results of the current research on the use of MSCs in the treatment of prostate cancer may be helpful to researchers and clinicians working in this field. Nevertheless, it is crucial to emphasize that although dual-role MSCs show promise as a therapeutic modality for managing prostate cancer, further investigation is imperative to comprehensively grasp their safety and effectiveness. Ongoing clinical trials are being conducted to assess the viability of MSCs in the management of prostate cancer. The results of these trials will help determine the viability of this approach. Based on the current literature, engineered MSCs-EV offer great potential for application in targeted tumor therapy.

[Effects of applying human umbilical cord mesenchymal stem cell exosomes through different pathways to treat full-thickness skin defect wounds in mice].

Objective: To investigate the effects of human umbilical cord mesenchymal stem cell (hUCMSC) exosomes in the treatment of full-thickness skin defect wounds in mice through local wound application, subcutaneous injection at the wound margin, and tail vein injection, and to explore the optimal administration route of hUCMSC exosomes for wound treatment. Methods: This study was an experimental study. hUCMSC exosomes were extracted from the discarded umbilical cord tissue of three normal delivery women aged 25-35 years in the Department of Obstetrics and Gynecology of Baogang Hospital of Inner Mongolia and successfully identified. Totally 120 male BALB/c mice aged 6-8 weeks were selected, and full-thickness skin defect wounds were prepared on the back of them. According to the random number table, the injured mice were divided into control group (without drug administration), local wound application group, wound margin subcutaneous injection group, and tail vein injection group (with 30 mice in each group). Mice in the latter three groups were given 0.2 mL phosphate buffer solution containing 200 µg hUCMSC exosomes by local wound application, subcutaneous injection at the wound margin, and tail vein injection, respectively. On post injury day (PID) 7, 14, and 21, the general condition of the wound was observed, and the wound healing rate was calculated; the wound tissue was collected, the pathological changes and collagen fibers were observed respectively by hematoxylin-eosin staining and Masson staining, the number of new microvessels was observed by CD31 immunohistochemical staining, and the content of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay. The sample number was 10 in each group at each time point. Results: On PID 7, 14, and 21, the wounds of mice in the 4 groups all healed gradually, and the wound healing of the mice in wound margin subcutaneous injection group was the best; the wound healing rates of mice in the three administration groups were significantly higher than those in control group (P<0.05), the wound healing rates of mice in wound margin subcutaneous injection group and tail vein injection group were significantly higher than those in local wound application group (P<0.05), and the wound healing rates of mice in wound margin subcutaneous injection group were significantly higher than those in tail vein injection group (P<0.05). On PID 7, 14, and 21, the growth and epithelialization speed of the wound tissue of mice in the three administration groups were significantly accelerated, and the collagen fibers in the wounds of mice in the three administration groups were larger in number and more neatly arranged in comparison with the control group. On PID 7, 14, and 21, under every 200-fold visual field, the number of new microvessels in the wound tissue of mice in local wound application group was 24.1±2.5, 50.7±4.1, and 44.2±2.3, respectively, the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group was 32.2±2.9, 67.5±4.9, and 53.6±3.7, respectively, and the number of new microvessels in the wound tissue of mice in tail vein injection group was 27.8±2.4, 59.1±3.7, and 49.6±2.6, respectively, which was significantly more than 20.6±1.7, 46.7±3.4, and 40.9±2.8 in control group (P<0.05); the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group and tail vein injection group was significantly more than that in local wound application group (P<0.05); the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group was significantly more than that in tail vein injection group (P<0.05). On PID 7, 14, and 21, the content of TNF-α and IL-6 in the wound tissue of mice in the three administration groups was significantly less than that in control group (P<0.05), the content of TNF-α and IL-6 in the wound tissue of mice in wound margin subcutaneous injection group and tail vein injection group was significantly less than that in local wound application group (P<0.05), and the content of TNF-α and IL-6 in the wound tissue of mice in wound margin subcutaneous injection group was significantly less than that in tail vein injection group (P<0.05). Conclusions: Local wound application, subcutaneous injection at the wound margin, and tail vein injection of hUCMSC exosomes can all promote the wound healing of full-thickness skin defects in mice through alleviating excessive inflammatory response and promoting angiogenesis. Among them, subcutaneous injection at the wound margin has a better therapeutic effect, indicating subcutaneous injection at the wound margin is the optimal administration route for hUCMSC exosomes in wound treatment.

Immunotherapy of M2 macrophage derived from exosome-based nanoparticles for spinal cord injury.

Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H2O2-induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible.

Stem Cell Secretions as a Potential Therapeutic Agent for Autism Spectrum Disorder: A Narrative Review.

Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by impaired social interaction and restricted repetitive behaviors or interests. The rising prevalence of ASD diagnosis has triggered a surge in research into investigating the underlying neuropathological processes and finding new therapeutic approaches. ASD is characterized by neuroinflammation and dysregulation of neuro-immune cross-talk, which suggests that stem cell treatment might be a potential therapeutic approach. The beneficial and restorative effects of stem cells are mainly due to their paracrine activity, in which stem cells generate and release extracellular vesicles such as exosomes and distinct secreted non-vesicle soluble proteins, including, growth factors, chemokines, cytokines, and immunomodulatory molecules referred to as the Secretome. In this paper, we reviewed the existing research exploring the therapeutic potential of stem cell secretome focusing on their role in addressing ASD pathology. Furthermore, we proposed a comprehensive mechanism of action for stem cell secretions, encompassing the broader secretome as well as the specific contribution of exosomes, in alleviating ASD neuropathology. Across the reviewed studies, exosomes and secreted soluble factors of the transplanted stem cell demonstrate a potential efficacy in ameliorating autistic-like behaviors. The proposed mechanism of action involves the modulation of signaling pathways implicated in neuroinflammation, angiogenesis, cellular apoptosis, and immunomodulation.