Mesenchymal stem cells osteogenic differentiation by ZnO nanoparticles and polyurethane bimodal foam nanocomposites.

Mesenchymal stem cells with tissue repair capacity involve in regenerative medicine. MSCs can promote bone repair when employed with nano scaffolds/particles. Here, the MTT and Acridine Orange assay enabled the cytotoxic concentration of Zinc oxide nanoparticles and Polyurethane evaluation. Following culturing adipose tissue-derived MSCs, ADSCs' proliferation, growth, and osteogenic differentiation in the presence of PU with and without ZnO NPs is tracked by a series of biological assays, including Alkaline Phosphatase activity, Calcium deposition, alizarin red staining, RT-PCR, scanning electron microscope, and immunohistochemistry. The results showed boosted osteogenic differentiation of ADSCs in the presence of 1% PU scaffold and ZnO NPS and can thus apply as a new bone tissue engineering matrix. The expression level of Osteonectin, Osteocalcin, and Col1 increased in PU-ZnO 1% on the 7th and 14th days. There was an increase in the Runx2 gene expression on the 7th day of differentiation in PU-ZnO 1%, while it decreased on day 14th. In conclusion, Polyurethane nano scaffolds supported the MSCs' growth and rapid osteogenic differentiation. The PU-ZnO helps not only with cellular adhesion and proliferation but also with osteogenic differentiation.

The role of copper chromite nanoparticles on physical and bio properties of scaffolds based on poly(glycerol-azelaic acid) for application in tissue engineering fields.

Tissue engineering combines suitable cells, engineering methods, and proper biochemical factors to develop functional and biological tissues and repair damaged tissues. In this study, we focused on synthesizing and characterizing a nanocomposite scaffold based on glycerol and azelaic acid (Gl-Az) combined with copper chromite (CuCr2O4) nanoparticles in order to increase the osteogenic differentiation efficiency of human adipose-derived stem cells (hADSCs) on fabricated scaffolds. The degradability and hydrophobicity properties as well as mechanical and thermal behaviors of nanocomposite scaffolds were investigated. Next, the cell toxicity of glycerol, azelaic acid and CuCr2O4 nanoparticles was studied by MTT assay test and acridine orange staining. Finally, the osteogenic differentiation of hADSCs on Gl-Az-CuCr2O4 scaffolds was examined using alkaline phosphatase activity (ALP) and calcium content. The obtained results demonstrated that Gl-Az-1%CuCr2O4 not only showed appropriate mechanical strength, biocompatibility and degradability but also influenced the capability of hADSCs to differentiate into osteogenic lineages. The hADSCs culture in Gl-Az-1%CuCr2O4 showed a significant increase in ALP activity levels and calcium biomineralization after 14 days of osteogenic differentiation. In conclusion, the Gl-Az-1%CuCr2O4 nanocomposite could be used as a biocompatible and degradable scaffold to induce the bone differentiation of hADSCs and it could be a promising scaffold in bone regenerative medicine.

Schizophyllan promotes osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells in vitro.

BACKGROUND: Bioactive polysaccharides are a promising way for bone disease prevention with high efficiency. Schizophyllan (SPG) is a polysaccharide derived from a species of fungus with anticancer, antitumor, and anti-inflammatory effects. In the present study, for the first time, the cell proliferation, osteogenic markers, mineral deposition, and osteogenic gene expression of human adipose tissue-derived mesenchymal stem cells (hADMSCs) grown on SPG were evaluated by in vitro assays. METHODS AND RESULTS: The cytotoxicity of SPG was measured using the MTT assay and acridine orange staining. Differentiation of hADMSCs was assessed using alkaline phosphatase (ALP) activity test, cellular calcium content assay, and mineralized matrix staining. To this end, Alizarin red S, von Kossa staining, and the expression of bone-specific markers, including ALP, Runx2, and osteonectin, were used by real-time RT-PCR over a 2-week period. According to the results, SPG at 10 µg/ml concentration was determined as the optimal dosage for differentiation studies. The results of osteogenic differentiation tests showed that compared to the control groups in vitro, SPG enhanced the osteogenic markers and mineralization as well as upregulation of the expression of bone specific genes in differentiated hADMSCs during differentiation. CONCLUSIONS: The results revealed that SPG could be applied as effective factor for osteogenic differentiation in the future. The current study provides insights into the hADMSC-based treatment and introduces promising therapeutic material for individuals who suffer from bone defects and injuries.

A novel co-culture assay to evaluate the effects of sympathetic innervation on vascular smooth muscle differentiation.

Dedifferentiation of vascular smooth muscle cells (VSMCs) from a functional phenotype to an inverse synthetic phenotype is a symptom of cardiovascular disorders, such as atherosclerosis and hypertension. The sympathetic nervous system (SNS) is an essential regulator of the differentiation of vascular smooth muscle cells (VSMCs). In addition, numerous studies suggest that SNS also stimulates VSMCs to retain their contractile phenotype. However, the molecular mechanisms for this stimulation have not been thoroughly studied. In this study, we used a novel in vitro co-culture method to evaluate the effective cellular interactions and stimulatory effects of sympathetic neurons on the differentiation of VSMCs. We co-cultured rat neural-like pheochromocytoma cells (PC12) and rat aortic VSMCs with this method. Expression of VSMCs contractile genes, including smooth muscle actin (acta2), myosin heavy chain (myh11), elastin (eln), and smoothelin (smtn), were determined by quantitative real-time-PCR analysis as an indicator of VSMCs differentiation. Fold changes for specific contractile genes in VSMCs grown in vitro for seven days in the presence (innervated) and absence (non-innervated) of sympathetic neurons were 3.5 for acta2, 6.5 for myh11, 4.19 for eln, and 4 for smtn (normalized to Tata Binding Protein (TBP)). As a result, these data suggest that sympathetic innervation promotes VSMCs' contractile gene expression and also maintains VSMCs' functional phenotype.

Ethics of Facial Transplantation: The Effect of Psychological Trauma Associated With Facial Disfigurement on Risk Acceptance and Decision Making.

OBJECTIVE: This study examines and contrasts the effect of risk disclosure on risk acceptance and perceived changes in quality of life (QoL) among individuals with and without facial disfigurement. SUMMARY OF BACKGROUND DATA: Psychological distress has been previously shown to alter patients' perception of certain treatments. Due to the grave risks and complications of FT, it is important to understand whether the psychological trauma associated with facial disfigurement alters their perception of FT and its associated risks. METHODS: Participants with and without facial disfigurement were recruited to complete a questionnaire about their perceived QoL, sense of identity, and willingness to proceed with FT in the context of 3 different hypothetical scenarios involving facial disfiguration. RESULTS: Four hundred nine nonfacially disfigured and 74 facially disfigured participants were included. When both healthy and facially disfigured individuals were presented with the risks and benefits of a FT, they both perceived their QoL to be as low, or significantly lower, than if they had severe facial disfigurement. Furthermore, presenting the risks of FT significantly altered the decision making and risk acceptance of healthy individuals with no facial disfigurement. However, risk disclosure did not affect the decision making among facially disfigured individuals. CONCLUSION: This study highlights that presenting the complication profile of FT decreases risk acceptance of FT in healthy individuals but has no significant effects on facially disfigured individuals. The psychological impact of facial disfigurement and its influence on accepting the significant risks of FT should be considered and warrants further investigation.

Anti-apoptotic effect of Nisin as a prebiotic on human mesenchymal stem cells in harsh condition.

Mesenchymal stem cells (MSCs) are progenitor cells of connective tissue with the ability of proliferation, self-renewal, and multilineage differentiation that make it a promising source with an enormous potential to be utilized for tissue repairing and vehicles of cell-based gene therapy. The low survival rate of MSCs following transplantation is their drawback. Preconditioning with some factors is a novel and effective strategy, improving the survival of the cells by protecting them from harmful conditions and result in the good recovery of injured tissues. Nisin is a prebiotic with antimicrobial activity. This manuscript aimed to evaluate the effect of Nisin preconditioning of MSCs on in vitro cell viability. MSCs were cultured and preconditioned with Nisin in different concentrations. Then, they are separately exposed to H2O2 and serum deprivation. Cell survival and cell apoptosis were evaluated by MTT assay and Real-time PCR, respectively. Furthermore, Annexin-PI staining and caspase activity was performed to visualize apoptotic cells. MSC-Nisin viability and proliferation significantly increased when exposed to H2O2 and serum deprivation, compared to that of MSCs. About 250 and 500 IU/mL of Nisin donate a significant anti-apoptotic impact to MSCs. Our data suggest that preconditioning with Nisin has been improved cell viability and the anti-apoptotic capacity of MSCs. However, the mechanism related to the protective properties of preconditioning and using this strategy in stem cell therapy requires more research.

Prevalence of zonulopathy in primary angle closure disease.

BACKGROUND: To determine the prevalence of zonulopathy in a large cohort of eyes with primary angle closure disease (PACD) that underwent cataract surgery. METHODS: Retrospective consecutive case series of PACD eyes (including primary angle closure suspect, primary angle closure, and primary angle closure glaucoma) that underwent phacoemulsification cataract surgery or clear lens extraction between 2009 and 2020 at a single ophthalmology centre. Those with risk factors for zonulopathy such as history of trauma, pseudoexfoliation syndrome, intraocular surgery, retinitis pigmentosa or connective tissue disorders were excluded. The primary outcomes included the prevalence of zonulopathy assessed intraoperatively and secondary pigment dispersion syndrome. RESULTS: In our cohort of 806 consecutive PACD eyes, the prevalence of zonulopathy was 7.3% (59 of 806 eyes) - significantly greater than the 0.46%-2.6% range reported for the general population (p < 0.001). Intraoperative signs of zonular weakness included floppy capsular bag (29 eyes, 3.6%), zonular laxity (25 eyes, 3.1%) and zonular dehiscence (11 eyes, 1.4%). Among these eyes, capsular tension ring was used in 23 eyes (39.0%), six eyes (10.2%) experienced vitreous prolapse intraoperatively and underwent anterior vitrectomy, and two eyes (3.4%) experienced posterior capsular rupture, one of which required a scleral-fixated intraocular lens. Secondary pigment dispersion syndrome was observed in 141 eyes (17.5%). CONCLUSIONS: This study evidenced a high prevalence of zonulopathy among a large cohort of PACD eyes and suggests zonulopathy as a possible under-recognised cause of angle closure. Until more sophisticated imaging modalities become available, awareness about the prevalence of zonulopathy in angle closure disease coupled with careful preoperative examinations can help minimise or prevent the complications of zonulopathy.

Cancer Therapy; Prospects for Application of Nanoparticles for Magnetic-Based Hyperthermia.

Hyperthermic therapy is defined as increasing the temperature of tumor tissues to 40-43 °C that has been effective approach for destroying malignant cells in the field of cancer therapy. Recent line of research has applied different approaches along with hyperthermic treatment to obtain high efficiency and little side effects. Magnetic nanoparticle-based hyperthermia has demonstrated an improved functionality in targeting malignant cells and implement their therapeutic role by heating the tumor cells. Here in this review article, we clarify the diverse aspects of magnetic nanoparticles in the treatment of cancer.

The effect of female sex steroid hormones on osteogenic differentiation of endometrial stem cells.

Bone regeneration is a significant and crucial health issue worldwide. Tissue bioengineering has shown itself to be the best substitute for common clinical treatment of bone loss. The suitable cell source is human endometrial stem cells (hEnSCs) which have several suitable characteristics for this approach. Since sex steroid hormones are involved in expansion and conservation of the skeleton, the effect of two sex steroid hormones known as estrogen (17-ß estradiol) and progesterone on osteogenic differentiation of hEnSCs were examined. For this purpose, hEnSCs were treated with 17-ß estradiol and progesterone separately (1 × 10-6 M) and simultaneously (1 × 10-7 M). Osteogenic differentiation tests including measurement of total mineral calcium content, Alizarin Red staining, the quantitative expression levels of some osteogenic markers by Real-time RT-PCR, and immunofluorescence staining were performed at 7 and 14 days of differentiation. To exhibit the morphology of the cells in osteogenic and culture medium, the hEnSCs were stained with Acridine Orange (AO) solution. In this research, MTT assay and AO staining revealed progesterone and 17-ß estradiol increase the proliferation of hEnSCs in a dose-dependent manner. Furthermore, the results of calcium content analysis, Real-time RT-PCR assay, and all tests of differentiation staining have shown that 17-ß estradiol and progesterone cannot induce hEnSCs' osteogenic differentiation. In conclusion, it is indicated that 17-ß estradiol and progesterone do not have positive effects on hEnSCs' osteogenic differentiation in vitro.

Tissue engineering scaffolds in the treatment of brain disorders in geriatric patients.

The world population is ageing at an alarming rate, currently increasing at around 3% per year for people over 60 years. This fast growing demography is largely unproductive and prone to many brain disorders such as Alzheimer's disease, Parkinson's disease, and brain tumors. Currently available treatment modalities are inadequate to stop neural degeneration or to completely eradicate cancer cells. Exogenously engineered scaffolds hold great potential for in vivo brain regeneration and functional restoration. Ideally, scaffolds for brain tissue engineering should be biocompatible, non-toxic, and electroactive with the ability to encourage neural elongation. These scaffolds have been successfully fabricated from a wide range of materials and techniques. Different types of stem cells have also been investigated for their ability to differentiate to nerve or glial tissue. The success of tissue engineering can thus be envisioned as a panacea for "retooling" of both individual's ability and for immense long-term benefit of society.

Generation of insulin-producing cells from human adipose-derived mesenchymal stem cells on PVA scaffold by optimized differentiation protocol.

The studies have been done on patient-specific human adipose-derived from mesenchymal stem cells (hADSCs) like a series of autologous growth factors and nanofibrous scaffolds (3D culture) will probably have many benefits for regenerative medicine in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a polyvinyl alcohol (PVA) scaffold and a differentiation protocol by adding platelet-rich plasma (PRP) that induces the hADSCs into insulin-producing cells (IPCs). The characteristics of the derived IPCs in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels. The viability of induced pancreatic cells was 14 days. The in vitro studies showed that the treatment of hADSCs in the 3D culture resulted in differentiated cells with strong characteristics of IPCs including pancreatic-like cells, the expression of the islet-associated genes at the mRNA and protein levels in comparison of 2D culture group. Furthermore, the immunoassay tests showed that these differentiated cells in these two groups are functional and secreted C-peptide and insulin in a glucose stimulation challenge. The results of our study for the first time demonstrated that the PVA nanofibrous scaffolds along with the optimized differentiation protocol with PRP can enhance the differentiation of IPCs from hADSCs. In conclusion, this study provides a new approach to the future pancreatic tissue engineering and beta cell replacement therapies for T1DM.

Nisin, a potent bacteriocin and anti-bacterial peptide, attenuates expression of metastatic genes in colorectal cancer cell lines.

Colorectal cancer is the third most common cause of cancer-related death in the world which genetic and environmental agents are responsible for cancer. When cells detach from the tumor and invade surrounding tissues, the tumor is malignant and may form secondary tumors at other locations in a process called metastasis. Probiotics are the largest group of inhabitation bacteria in the colon. Gut microbiota has a central role in prevented the risk colon cancer. Probiotics are beneficial microorganisms, like Lactic acid bacteria and Lactobacilli bacteria which are using in the dairy industry. Probiotics nisin are having the most important category of safe usage. In this study LS180, SW48, HT29 and Caco2 was cultured and treated with different dose of nisin. Cell proliferation was assayed with MTT. The expression of CEA, CEAM6 and MMP2F genes was analyzed with Real-time PCR. Protein expression of CEA was evacuated with ELISA. Our result was shown that the 40-50 IU/mL nisin could suppress proliferation of LS180. Cell proliferation of SW48, HT29, Caco2 cells was decreased in 250-350 IU/mL concentration of nisin. The gene expression of CEA, CEAM6, MMP2F was significantly down-regulated with nisin treatment (p < 0.001, p < 0.01). Also, after cells treated with nisin, CEA protein expression was down regulated (p < 0.01). In conclusion, nisin could suppressed metastatic process via down-regulation of CEA, CEAM6, MMP2F, MMP9F genes. We suggested the new treatment strategies beyond Probiotics, which play a role in the prevention local tumor invasion, metastasis and recurrence.

Hardystonite-Coated Poly(l-lactide) Nanofibrous Scaffold and Efficient Osteogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells.

In this study, a ceramic-coated nanofibrous scaffold has been fabricated to biomimic the microstructure of natural extracellular matrix and the stiffening inorganic compartment of bone. Poly-l-lactic acid (PLLA) nanofibers were electrospun and exposed to oxygen plasma to induce hydrophilicity and promote ceramic adsorption. Hardystonite (HS), which possesses superior osteoinduction potential over hydroxyapatite, was coated on plasma-treated PLLA nanofibers by drenching the nanofibers in HS suspension. Pure and composite PLLA-based scaffolds were characterized in terms of physical and biological properties. In vitro cultivation of adipose-derived mesenchymal stem cells (AMSCs) on the scaffolds displayed that the composite scaffold is able to further support cell attachment and proliferation. In case of osteogenic differentiation of AMSCs, HS coating significantly increased the synthesis and activity of alkaline phosphate over 21 days period. In addition, the composite scaffold showed improved mineralization. The expression level of osteonectin and osteocalcin genes was significantly enhanced by HS coating of nanofibers. The biological improvement of PLLA nanofibrous matrix in the presence of HS nanoparticles could either be attributed to the release and stimulatory effect of constituent ions of HS or to the modification of chemico-physical properties of the resultant ceramic by silicon and zinc present in HS.

The effect of transplanted human Wharton's jelly mesenchymal stem cells treated with IFN-γ on experimental autoimmune encephalomyelitis mice.

Interferon gamma (IFN-γ) increases the immunosuppressive property of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs). In this study, we evaluated the therapeutic effects of IFN-γ primed WJ-MSCs in EAE mice. IFN-γ primed WJ-MSCs were injected on days 3 and 11 after EAE induction. 21 days after EAE induction, splenocytes and cervical lymph node cells were isolated and cell proliferation, secretion of inflammatory cytokines and frequency of regulatory T-cells was measured. On day 50 of the study, cell infiltration and gene expression of inflammatory cytokines in brain of mice were studied. Leukocyte infiltration and symptoms were significantly reduced in IFN-γ primed WJ-MSCs treated group compared to other groups. These cells showed significantly reduced proliferation and increased Treg cells as well as decreased secretion and gene expression of inflammatory cytokines in EAE mice. Our data suggest that IFN-γ may be used to stimulate the immunomodulatory property of WJ-MSCs in clinical situations.

Osteoblast differentiation of mesenchymal stem cells on modified PES-PEG electrospun fibrous composites loaded with Zn2SiO4 bioceramic nanoparticles.

Tissue engineering has attracted a great deal of interest by combining fibrous scaffolds and stem cells regarding bone regeneration applications. In the present study, polymeric fibrous polyethersulphone-polyethylene glycol (PES-PEG) was fabricated by electrospinning. It was then treated with NH3 plasma to enhance surface hydrophilicity, cell attachment, growth and differentiation potential. X-ray photoelectron spectroscopy (XPS) measurements were used to evaluate the modification of the scaffold's surface chemistry. Electrospun scaffolds were coated with willemite (Zn2SiO4) bioceramic nanoparticles. Scaffold characterization was done by scanning electron microscope (SEM), differential scanning calorimetry (DSC), contact angle measurements and tensile analysis. MTT assay was used to assess the biocompatibility of fibrous scaffolds loaded with Zn2SiO4 regarding proliferation support. Osteogenic differentiation of cultured human mesenchymal stem cells (hMSCs) on fibers was evaluated using common osteogenic markers such as alkaline phosphatase (ALP) activity, calcium mineral deposition, quantitative real-time PCR (qPCR) and immunocytochemical analysis (ICC). According to the results, proliferation and osteogenic differentiation of hMSCs were significantly enhanced after coating Zn2SiO4 on fibrous scaffolds. These results were detected by higher ALP activity, biomineralization and expression of osteogenic related genes and proteins in differentiated hMSCs. In conclusion, our results indicated that the combination of Zn2SiO4 nanoparticles and electrospun fibers is able to provide a new, suitable and more efficient matrix to support stem cells differentiation for bone tissue engineering applications.

Comparison of different protocols for neural differentiation of human induced pluripotent stem cells.

Although embryonic stem cells (ESCs) have enormous potentials due to their pluripotency, their therapeutic use is limited by ethical, biological and safety issues. Compared to ESCs, induced pluripotent stem cells (iPSCs) can be obtained from mouse or human fibroblasts by reprogramming. Numerous studies have established many protocols for differentiation of human iPSCs (hiPSCs) into neural lineages. However, the low differentiation efficiency of such protocols motivates researchers to design new protocols for high yield differentiation. Herein, we compared neural differentiation potential of three induction media for conversion of hiPSCs into neural lineages. In this study, hiPSCs-derived embryoid bodies were plated on laminin coated dishes and were treated with three induction media including (1) bFGF, EGF (2) RA and (3) forskolin, IBMX. Immunofluorescence staining and quantitative real-time PCR (qPCR) analysis were used to detect the expression of neural genes and proteins. qPCR analysis showed that the expression of neural genes in differentiated hiPSCs in forskolin, IBMX supplemented media was significantly higher than undifferentiated cells and those in induction media containing bFGF, EGF or RA. In conclusion, our results indicated a successful establishment protocol with high efficiency for differentiation of hiPSCs into neural lineages.

Osteogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells on Composite Polymeric Scaffolds: A Review.

The mesenchymal stem cells (MSCs) are the fundamental part of bone tissue engineering for the emergence of reconstructive medicine. Bone tissue engineering has recently been considered a promising strategy for treating bone diseases and disorders. The technique needs a scaffold to provide an environment for cell attachment to maintain cell function and a rich source of stem cells combined with appropriate growth factors. MSCs can be isolated from adipose tissue (ASCs), bone marrow (BM-MSCs), or umbilical cord (UC-MSCs). In the present study, the potential of ASCs to stimulate bone formation in composite polymeric scaffolds was discussed and it showed that ASCs have osteogenic ability in vitro. The results also indicated that the ASCs have the potential for rapid growth, easier adipose tissue harvesting with fewer donor site complications and high proliferative capacity. The osteogenic differentiation capacity of ASCs varies due to the culture medium and the addition of factors that can change signaling pathways to increase bone differentiation. Furthermore, gene expression analysis has a significant impact on improving our understanding of the molecular pathways involved in ASCs and, thus, osteogenic differentiation. Adding some drugs, such as dexamethasone, to the biomaterial composite also increases the formation of osteocytes. Combining ASCs with scaffolds synthesized from natural and synthetic polymers seems to be an effective strategy for bone regeneration. Applying exopolysaccharides, such as schizophyllan, chitosan, gelatin, and alginate in composite scaffolds enhances the osteogenesis potential of ASCs in bone tissue regeneration.

Canadian legal cases in ophthalmology: a closer look at 40 years' worth of data.

OBJECTIVE: To assess the characteristics of malpractice lawsuits against Canadian ophthalmologists and the predisposing factors leading to claims. DESIGN: Retrospective case series. METHODS: A systematic search of the 2 largest Canadian online legal databases, LexisNexis Canada and Westlaw Canada, was performed to collect cases against ophthalmologists in Canadian courts from 1977 to 2021. RESULTS: This study comprised 68 legal cases, including 52 lawsuits, 14 cases appealed once, and 2 cases appealed twice. Most cases concerned surgical procedures (46.2%), followed by misdiagnoses or lack thereof (32.7%) and nonsurgical procedures (21.2%). Half the cases (n = 26) were immediately dismissed by the judge in favour of the ophthalmologist, though among the remaining half that proceeded to trial the majority (88.5%) were won by the patients. All appeals by patients were dismissed by the judge. The median monetary value of damages awarded was $308,202. CONCLUSIONS: This study is the first to report on ophthalmology-involved medical litigation cases in Canada. Most cases were ruled in favour of the ophthalmologist, but most of those that were not immediately dismissed by the judge were ruled in favour of the plaintiff. Notably, a plurality of these cases argued for a lack of informed consent, and every case in which a lack was successfully pleaded was ruled in favour of the plaintiff, highlighting the importance of appropriate informed consent. The findings of this study give Canadian ophthalmologists insight into areas of practice that commonly lead to litigation and can aid in improving clinical practice and risk management.

Potential therapeutic effects and nano-based delivery systems of mesenchymal stem cells and their isolated exosomes to alleviate acute respiratory distress syndrome caused by COVID-19.

The severe respiratory effects of the coronavirus disease 2019 (COVID-19) pandemic have necessitated the immediate development of novel treatments. The majority of COVID-19-related fatalities are due to acute respiratory distress syndrome (ARDS). Consequently, this virus causes massive and aberrant inflammatory conditions, which must be promptly managed. Severe respiratory disorders, notably ARDS and acute lung injury (ALI), may be treated safely and effectively using cell-based treatments, mostly employing mesenchymal stem cells (MSCs). Since the high potential of these cells was identified, a great deal of research has been conducted on their use in regenerative medicine and complementary medicine. Multiple investigations have demonstrated that MSCs and their products, especially exosomes, inhibit inflammation. Exosomes serve a critical function in intercellular communication by transporting molecular cargo from donor cells to receiver cells. MSCs and their derived exosomes (MSCs/MSC-exosomes) may improve lung permeability, microbial and alveolar fluid clearance, and epithelial and endothelial repair, according to recent studies. This review focuses on COVID-19-related ARDS clinical studies involving MSCs/MSC-exosomes. We also investigated the utilization of Nano-delivery strategies for MSCs/MSC-exosomes and anti-inflammatory agents to enhance COVID-19 treatment.