Application of stem cells in tissue engineering for defense medicine

The dynamic nature of modern warfare,including threats and injuries faced by soldiers,necessitates the development of countermeasures that address a wide variety of injuries.Tissue engineering has emerged as a field with the potential to provide contemporary solutions.In this review,discussions focus on the applications of stem cells in tissue engineering to address health risks frequently faced by combatants at war.Human development depends intimately on stem cells,the mysterious precursor to every kind of cell in the body that,with proper instruction,can grow and differentiate into any new tissue or organ.Recent reports have suggested the greater therapeutic effects of the anti-inflammatory,trophic,paracrine and immune-modulatory functions associated with these cells,which induce them to restore normal healing and tissue regeneration by modulating immune reactions,regulating inflammation,and suppressing fibrosis.Therefore,the use of stem cells holds significant promise for the treatment of many battlefield injuries and their complications.These applications include the treatment of injuries to the skin,sensory organs,nervous system tissues,the musculoskeletal system,circulatory/pulmonary tissues and genitals/testicles and of acute radiation syndrome and the development of novel biosensors.The new research developments in these areas suggest that solutions are being developed to reduce critical consequences of wounds and exposures suffered in warfare.Current military applications of stem cell-based therapies are already saving the lives of soldiers who would have died in previous conflicts.Injuries that would have resulted in deaths previously now result in wounds today;similarly,today’s permanent wounds may be reduced to tomorrow’s bad memories with further advances in stem cell-based therapies.

Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.

Effect of aging on stem cells

Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of agingassociated disorders, but also in future development of novel effective stem cell-based therapies to treat agingassociated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects.

Formulating etoposide in a nanoemulsion containing polyunsaturated fatty acids potentiates its anti-proliferation and anti-invasion activities against the ovarian cancer cells

Inorporation of etoposide(ETP)into nanoemulsion(NE)containing polyunsaturated faty adids(PUFAS)may potentially augment its antiproliferation efet on the cancer cll The current study aimed to examine the in vitro antitumor activity of a novel formulation(ETP-BC/EP-NE)produced by combining the anticancer drug(ETP)with NE(BCEP-NE)consisting of the blasck currant seed and organic ewening primrose oils.The produced formulas were physically charaterized using 2etasizer measurements.Thelr ceytotoxkc efect was testfied at concentrations ranges from 0.0001 to 5μM using CCK-8.Apoptotic and ant-invasion efects were evaluated using the assays of mitochondrtal membrane potental,annexin V-FITC double staining.DNA fragmentation,and collagen-based cell invasion.According to the zetasizer charaterization,the nano-suspensions of ETP-BC/EP-NE have z-average diameters of 87.63土3.30 nm with an average surface zeta potential of-0.605土0.003 mV.A reduction of 50%in the growth of SK-OV-3 cells was found at a distinetly lower concentration of ETP-BCEP-NE(IlCso=0.04土0.2μM)than that of ETP(ICsu=4.75土0.1μM).Resuts indicated that FTP-BCIEP-NE had a greater apoptotic ffect than FTP on SK-OV-3 cllsl which was attibuted to the larger amount of late apoptotic cells(41.9土1.05%)higher loss of mitochondrial membrane potential,and more intensive fragmented DNA The ETP-BC/EP-NE treatment suppressed the cllular invasion by 55%,whereas EIP impeded the ellular invasion by only 3%,Formulting ETP with PUFAs in NE had ameliorated the efcacy of ETP.

MicroRNAs and JAK/STAT3 signaling:A new promising therapeutic axis in blood cancers

Blood disorders include a wide spectrum of blood-associated malignancies resulting from inherited or acquired defects.The ineffectiveness of existing therapies against blood disorders arises from different reasons,one of which is drug resistance,so different types of leukemia may show different responses to treatment.Leukemia occurs for a variety of genetic and acquired reasons,leading to uncontrolled proliferation in one or more cell lines.Regarding the genetic defects,oncogene signal transducer and activator of transcription(STAT)family transcription factor,especially STAT3,play an essential role in hematological disorders onset and progress upon mutations,dysfunction,or hyperactivity.Besides,microRNAs,as biological molecules,has been shown to play a dual role in either tumorigenesis and tumor suppression in various cancers.Besides,a strong association between STAT3 and miRNA has been reported.For example,miRNAs can regulate STAT3 via targeting its upstream mediators such as IL6,IL9,and JAKs or directly binding to the STAT3 gene.On the other hand,STAT3 can regulate miRNAs.In this review study,we aimed to determine the role of either microRNAs and STAT3 along with their effect on one another's activity and function in hematological malignancies.

Electromagnetic field exposure as a plausible approach to enhance the proliferation and differentiation of mesenchymal stem cells in clinically relevant scenarios

Mesenchymal stem/stromal cell(MSC)-based therapy has been regarded as one of the most revolutionary breakthroughs in the history of modern medicine owing to its myriad of immunoregulatory and regenerative properties.With the rapid progress in the fields of osteo-and musculoskeletal therapies,the demand for MSC-based treatment modalities is becoming increasingly prominent.In this endeavor,researchers around the world have devised new and innovative techniques to support the proliferation of MSCs while minimizing the loss of hallmark features of stem cells.One such example is electromagnetic field(EMF)exposure,which is an alternative approach with promising potential.In this review,we present a critical discourse on the efficiency,practicability,and limitations of some of the relevant methods,with insurmountable evidence backing the implementation of EMF as a feasible strategy for the clinically relevant expansion of MSCs.