Cell Animal Models Research Articles

Mesenchymal stem cells and induced pluripotent stem cells as therapies for multiple sclerosis.

Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC) and induced pluripotent stem cell (iPSCs) derived precursor cells can modulate the autoimmune response in the central nervous system (CNS) and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS.

Phenotypic switching of vascular smooth muscle cells in animal model of rat thoracic aortic aneurysm.

To explore if there is phenotypic switching in the vascular smooth muscle cells (vSMCs) of rat thoracic aortic aneurysms and the role it plays in the process of aneurysm formation. Male SD white rats were assigned randomly to the aneurysm group (AG) and control group (CG). The animal aneurysm model was obtained by soaking the peri-adventitia with porcine pancreatic elastase (PPE). The rats in the CG were given saline to provide contrast. A vascular ultrasound was used to monitor the diameter of the aneurysm. Specimens were stained with haematoxylin and eosin (HE), and α-SMA, SM-MHC, matrix metalloproteinase (MMP)-2 and MMP-9 were detected with immunohistochemistry staining. α-SMA, SM-MHC, MMP-2 and MMP-9 were conducted with western blot. vSMCs taken from the descending aorta of both of the CG and AG were separated and cultured until Passage 3. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method were used to analyse cell proliferation. Western blot was used to evaluate MMP-2, MMP-9 expression and flow cytometry was employed to assess cell apoptosis. Vascular ultrasound showed obvious dilatation of soaked descending aorta. HE staining showed thickening of thoracic aorta and disarrangement of cells after soaking with PPE. Immunohistochemistry staining showed high expression of MMP-2 and MMP-9 but low expression of SM-MHC and α-SMA in the AG. Tissue western blot analysis of the AG showed that the protein gray value was high in MMP-2 and MMP-9, but low in α-SMA and SM-MHC, which had statistical differences compared with CG with a P-value of <0.05. MTT analysis showed vSMC proliferation activity was higher in the AG than in the CG. Flow cytometry analysis revealed that cell apoptosis between the control and aneurysm groups had significant statistical differences. There is vSMC phenotypic switching in animal models as seen through the rat thoracic aortic aneurysms. This may play an important role in the formation of aneurysms. Our findings are relevant to human aneurysms and may be conducive in the research of aortic aneurysm pathology and treatment.

Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson's disease model.

Recent studies have shown evidence of behavioral recovery after transplantation of human pluripotent stem cell (PSC)-derived neural cells in animal models of neurological disease. However, little is known about the mechanisms underlying graft function. Here we use optogenetics to modulate in real time electrophysiological and neurochemical properties of mesencephalic dopaminergic (mesDA) neurons derived from human embryonic stem cells (hESCs). In mice that had recovered from lesion-induced Parkinsonian motor deficits, light-induced selective silencing of graft activity rapidly and reversibly re-introduced the motor deficits. The re-introduction of motor deficits was prevented by the dopamine agonist apomorphine. These results suggest that functionality depends on graft neuronal activity and dopamine release. Combining optogenetics, slice electrophysiology and pharmacological approaches, we further show that mesDA-rich grafts modulate host glutamatergic synaptic transmission onto striatal medium spiny neurons in a manner reminiscent of endogenous mesDA neurons. Thus, application of optogenetics in cell therapy can link transplantation, animal behavior and postmortem analysis to enable the identification of mechanisms that drive recovery.

Recurrent urinary tract infections in children: Preventive interventions other than prophylactic antibiotics.

Urinary tract infection (UTI) is one of the most common childhood infections. Permanent renal cortical scarring may occur in affected children, especially with recurrent UTIs, leading to long-term complications such as hypertension and chronic renal failure. To prevent such damage, several interventions to prevent UTI recurrences have been tried. The most established and accepted prevention at present is low dose long-term antibiotic prophylaxis. However it has a risk of break through infections, adverse drug reactions and also the risk of developing antibiotic resistance. The search is therefore on-going to find a safer, effective and acceptable alternative. A recent meta-analysis did not support routine circumcision for normal boys with no risk factors. Vaccinium Macrocarpon (cranberry), commonly used against UTI in adult women, is also effective in reducing the number of recurrences and related antimicrobial use in children. Sodium pentosanpolysulfate, which prevents bacterial adherence to the uroepithelial cells in animal models, has shown conflicting results in human trials. When combined with antibiotic, Lactobacillus acidophilus (LA-5) and Bifidobacterium, by blocking the in vitro attachment of uropathogenic bacteria to uroepithelial cells, significantly reduce in the incidence of febrile UTIs. Deliberate colonization of the human urinary tract of patients with recurrent UTI with Escherichia-coli (E. coli) 83972 has resulted in subjective benefit and less UTI requiring treatment. The non-pathogenic E. coli isolate NU14 DeltawaaL is a candidate to develop live-attenuated vaccine for the treatment and prevention of acute and recurrent UTI. Diagnosing and treating dysfunctional elimination syndromes decrease the incidence of recurrent UTI. A meta-analysis found the lack of robust prospective randomized controlled trials limited the strength of the established guidelines for surgical management of vesicoureteral reflux. In conclusion, several interventions, other than antibiotic prophylaxis, for the prevention of recurrent UTI have been tried and, although showing some promise, they do not provide so far a definitive effective answer. Finding suitable alternatives still requires further high quality research of those seemingly promising interventions.

Osteogenic Potential of Dental Mesenchymal Stem Cells in Preclinical Studies: A Systematic Review Using Modified ARRIVE and CONSORT Guidelines.

Background and Objective. Dental stem cell-based tissue engineered constructs are emerging as a promising alternative to autologous bone transfer for treating bone defects. The purpose of this review is to systematically assess the preclinical in vivo and in vitro studies which have evaluated the efficacy of dental stem cells on bone regeneration. Methods. A literature search was conducted in Ovid Medline, Embase, PubMed, and Web of Science up to October 2014. Implantation of dental stem cells in animal models for evaluating bone regeneration and/or in vitro studies demonstrating osteogenic potential of dental stem cells were included. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to ensure the quality of the search. Modified ARRIVE (Animal research: reporting in invivo experiments) and CONSORT (Consolidated reporting of trials) were used to critically analyze the selected studies. Results. From 1914 citations, 207 full-text articles were screened and 137 studies were included in this review. Because of the heterogeneity observed in the studies selected, meta-analysis was not possible. Conclusion. Both in vivo and in vitro studies indicate the potential use of dental stem cells in bone regeneration. However well-designed randomized animal trials are needed before moving into clinical trials.

Amniotic fluid-derived stem cells as an effective cell source for transplantation therapy in stroke

This review examines stem cells harvested from human amniotic fluid and considers their possible applications in regenerative medicine, specifically for stroke therapy. Providing an early-stage, highly differentiable source of mesenchymal stem cells, amniotic fluid shows the potential to be effective in the development of future stem cell-based transplantation. This paper underscores the importance of pursuing amniotic fluid as a stem cell source in stroke therapy, citing both the characteristics and the demonstrated functional benefits of these cells in animal models. Additional research is required to discover the full range of amniotic fluid-derived stem cells' (AFSCs) applications but these cells have thus far demonstrated the ability to be applied to a wide array of existing and future treatment methods. Both amniotic fluid- and amnion membrane-derived stem cells (AMSCs) have their merits, and this assessment will accordingly provide a comparison of the benefits and drawbacks of both cell sources.

Icariin intervenes in cardiac inflammaging through upregulation of SIRT6 enzyme activity and inhibition of the NF-kappa B pathway.

The aim of the study was to investigate the effect of icariin (ICA) on cardiac aging through its effects on the SIRT6 enzyme and on the NF-κB pathway. Investigating the effect of ICA on the enzymatic activity of histone deacetylase SIRT6 revealed a concentration of 10−8 mol/L ICA had a maximum activating effect on histone deacetylase SIRT6 enzymatic activity. Western analysis showed that ICA upregulated SIRT6 protein expression and downregulated NF-κB (p65) protein expression in animal tissues and cell models. ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF-κB inflammatory signaling pathways as shown by decreasing mRNA levels of the NF-κB downstream target genes TNF-α, ICAM-1, IL-2, and IL-6. Those effects were mediated directly or indirectly by SIRT6. We provided evidence that inflammaging may involve a novel link between the effects of ICA on SIRT6 (a regulator of aging) and NF-κB (a regulator of inflammation).

Gap junctional communication in health and disease.

Gap junctional communication in health and disease.

Structure-guided development of deoxycytidine kinase inhibitors with nanomolar affinity and improved metabolic stability.

Recently, we have shown that small molecule dCK inhibitors in combination with pharmacological perturbations of de novo dNTP biosynthetic pathways could eliminate acute lymphoblastic leukemia cells in animal models. However, our previous lead compound had a short half-life in vivo. Therefore, we set out to develop dCK inhibitors with favorable pharmacokinetic properties. We delineated the sites of the inhibitor for modification, guided by crystal structures of dCK in complex with the lead compound and with derivatives. Crystal structure of the complex between dCK and the racemic mixture of our new lead compound indicated that the R-isomer is responsible for kinase inhibition. This was corroborated by kinetic analysis of the purified enantiomers, which showed that the R-isomer has >60-fold higher affinity than the S-isomer for dCK. This new lead compound has significantly improved metabolic stability, making it a prime candidate for dCK-inhibitor based therapies against hematological malignancies and, potentially, other cancers.

Dual targeting of the tumor and its associated vasculature using a single bispecific chimeric antigen receptor molecule

Meeting abstracts We have previously demonstrated the efficacy of HER2 specific chimeric antigen receptor (CAR) T cells in animal models of human cancer. While HER2 CAR T cells induced tumor regression, tumors recurred in a subset of animals. Lytic co-targeting of the tumor endothelium could

Interaction of human telomeric G-quadruplex DNA with thymoquinone: A possible mechanism for thymoquinone anticancer effect

BackgroundThymoquinone (TQ) has been documented to possess chemo-preventive and chemotherapeutic antitumor effects. Studies reported that TQ inhibits the growth of cancer cells in animal models, culture and xenografted tumors. Molecular mechanisms underlying these anticancer effects were attributed to inductions of cell cycle arrest, apoptosis, oxidative damage of cellular macromolecules, blockade of tumor angiogenesis and inhibitions in migration, invasion and metastasis of cancer cells.On the other hand, human telomere DNA plays a role in regulating genes' transcriptions. It folds up into G-quadruplex structures that inhibit telomerase enzyme over-expressed in cancerous cells. Molecules that selectively stabilize G-quadruplex are potential anticancer agents. Therefore, this work aimed to explore the interaction of TQ with G-quadruplex DNA as a possible underlying mechanism for the anticancer effect of TQ. MethodsInteractions of TQ with telomeric G-quadruplex (5′-AGGG(TTAGGG)3-3′) and duplex DNAs were studied using UV–vis, fluorescence, circular dichroism, liquid and solid NMR (1H and 13C), melting temperature and docking simulation. ResultsChanges in UV–vis, CD, fluorescence, 1H NMR and 13C NMR, spectra as well as melting temperatures and docking simulations provided evidences for TQ's interactions with G-quadruplex. TQ was found to interact with G-quadruplex on two binding sites adjacent to the TTA loop with binding constants 1.80×105 and 1.12×107M−1. Melting temperatures indicated that TQ stabilized G-quadruplex by 5.6°C and destabilized ct-DNA by 5.1°C. Selectivity experiment indicated that TQ is preferentially binding to G-quadruplex over duplex with selectivity coefficients of 2.80–3.33×10−3. Results suggested an intercalation binding mode based on π–π stacking. ConclusionOur results propose that TQ can possibly act as a G-quadruplex DNA stabilizer and subsequently contribute to the inhibition of telomerase enzyme and cancer's proliferation. General significanceOur results represent a change in the paradigms reported for structural features of G-quadruplex's stabilizers and anticancer mechanisms of TQ.

Using Augmented Reality to Bring interactivity to Metabolism Teaching

Visual literacy is the ability to understand (read) and use (write) images and to think and learn regarding images (both static and moving). Visual literacy and visualization are key learning components in the biochemistry because that science uses models of molecules to explain how cells work. Many studies have shown that visualization technologies (VT) can be useful to develop essential visual literacy. The term “mixed reality” can be defined as the merging of real and virtual worlds to produce new environments and visualizations where physical and digital objects co-exist and interact in real time. The VT taps the brain's inherent ability to process visual information rapidly, identify patterns and sense order in complex situations generally making the complex simpler. OBJECTIVES: Design a Mixed Reality (MR) application named VRMET to help the development of visual literacy skills to understand and represent biochemical concepts. MATERIALS AND METHODS: VRMET app was developed using Unity3D, Vuforia Augmented Reality SDK and Google VR SDK for Unity. 3D molecules were obtained from Protein Data Bank and ChemSpider and optimized using Blender. VRMET uses a 3D scaled animal cell model. RESULTS AND DISCUSSION: VRMET requires a device with a camera. The user can get the App from the Google Play Store. VRMET has two different scenes: the Augmented reality (AR) scene and the Virtual Reality (VR) scene. AR Allows visualizing, from various angles, a scale model of an animal cell. VR allows one to realize a biochemical route within the cellular model, visualizing each one of the organelles and observing each of the reactions of glycolysis and the Krebs cycle. CONCLUSIONS: VRMET allows students to visualize the molecular structure of substrates and products, thus perceiving changes in each molecule along the metabolic pathway. It also allows observing where in the cell each metabolic pathway occurs.

Conversion From Tacrolimus to Sirolimus Results in Expansion of CD4+25hiFoxp3+ T Cells.

Background: Tacrolimus(TAC) and Sirolimus(SRL) are commonly used immunosuppressive drugs in kidney transplantation. SRL has been shown to induce the expansion of regulatory T cells in animal models and human cell cultures but the data in clinical trials are scarce. Methods: This study included 30 renal transplant recipients from a randomized trial of SRL conversion (n=18) or TAC maintenance (n=12). The conversion started at 12 months post-transplant. Peripheral blood mononuclear cells were collected at 0 (baseline), 6, 12 and 24 months post-randomization. T cell subpopulations were analyzed by flow cytometry. Median fluorescent intensity (MFI) of Foxp3 was analyzed by flowjo v10 software. Results: At baseline, the frequencies of CD4+25hiFoxp3+ T cells were similar in both groups (0.25±0.04(SRL) VS 0.39±0.07(TAC) % of PBMC, p=0.10). SRL conversion led to a significant increase in CD4+25hiFoxp3+ T cells at 6, 12 and 24 months post conversion (0.81±0.10(SRL) VS 0.29±0.05(TAC) % of PBMC at 6 months, 0.67±0.10(SRL) VS 0.26±0.06(TAC) % of PBMC at 12 months and 1.58±0.09(SRL) VS 0.13±0.02(TAC) % of PBMC at 24 months (p<0.01 at all time point)).Figure: No Caption available.No frequency difference was observed in other T cell subpopulations. The MFI of foxp3 in CD4+25hiFoxp3+ T cells was comparable in both groups from baseline (105.8±14.3(SRL) VS 112.1±25.8(TAC), p=0.82) to 24 months (75.0±7.1(SRL) VS 98.1±10.8(TAC), p=0.07) post conversion. Conclusion: Switching from TAC to SRL results in a gradual expansion of CD4+25hiFoxp3+ T cells from 6 to 24 months. No significant different in Foxp3 MFI expression was observed between TAC and SRL group suggesting a true increase in regulatory T cells in SRL group. These results might have a clinical impact on immunosuppressive drug selection in kidney transplant patients.

The Latest News in Movement Disorders: Steps Forward and Back

This article reviews several recent studies using focused ultrasound to facilitate treatment of movement disorders and commented on its future. Also discussed are recent Phase 3 studies that assessed disease modification in patients with Parkinson's disease (PD), novel technologies to understand the role of circuits and cells in animal models of movement disorders, and the role of leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), and parkin as genetic risk factors in sporadic PD.

Blockade of type I interferon (IFN) production by retroviral replicating vectors and reduced tumor cell responses to IFN likely contribute to tumor selectivity.

We developed a Moloney mouse leukemia virus (MLV)-based retroviral replicating vector (RRV), Toca 511, which has displayed tumor specificity in resected brain tumor material and blood in clinical trials. Here, we investigated the interaction between Toca 511 and human host cells, and we show that RRVs do not induce type I interferon (IFN) responses in cultured human tumor cells or cultured human primary cells. However, exogenous type I IFN inhibited RRV replication in tumor cells and induced IFN-regulated genes, albeit at a lower level than in primary cells. Unexpectedly, RRVs did not induce IFN-α production upon incubation in vitro with human plasmacytoid dendritic cells (pDCs), whereas lentivirus vector and heat-treated RRVs did. Coincubation of RRVs with heat-treated RRVs or with lentivirus vector suppressed IFN-α production in pDCs, suggesting that native RRV has a dominant inhibitory effect on type I IFN induction. This effect is sensitive to trypsin treatment. In addition, heat treatment inactivated that activity but exposed an immune-stimulatory activity. The immune-stimulating component is sensitive to deglycosidases, trypsin, and phospholipase C treatment. Experiments with retroviral nonreplicating vectors and virus-like particles demonstrated that the immunosuppressive activity is not associated with the amphotropic envelope or the glyco-Gag protein. In summary, our data provide evidence that RRVs do not directly trigger type I IFN responses in IFN-responsive tumor cells. Moreover, RRVs appear to carry a heat-labile component that actively suppresses activation of cellular innate immune responses in pDCs. Inhibition of IFN induction by RRVs and the reduced response to IFN should facilitate tumor-specific infection in vivo. RRVs have a convincing preference for replicating in tumor cells in animal models, and we observed similar preferences in the initial treatment of human glioblastoma patients. This study investigates the basis for the interaction between RRV and human host cells (tumor versus nontumor) in vitro. We found that RRVs do not trigger an IFN-α/β response in tumor cells, but the cells are capable of responding to type I IFNs and of producing them when stimulated with known agonists. Surprisingly, the data show that RRVs can actively inhibit induction of cellular innate immunity and that this inhibitory activity is heat labile and trypsin sensitive and not attributable to the envelope protein. These data partially explain the observed in vivo tumor specificity.

A semi-automated technique for labeling and counting of apoptosing retinal cells.

BackgroundRetinal ganglion cell (RGC) loss is one of the earliest and most important cellular changes in glaucoma. The DARC (Detection of Apoptosing Retinal Cells) technology enables in vivo real-time non-invasive imaging of single apoptosing retinal cells in animal models of glaucoma and Alzheimer’s disease. To date, apoptosing RGCs imaged using DARC have been counted manually. This is time-consuming, labour-intensive, vulnerable to bias, and has considerable inter- and intra-operator variability.ResultsA semi-automated algorithm was developed which enabled automated identification of apoptosing RGCs labeled with fluorescent Annexin-5 on DARC images. Automated analysis included a pre-processing stage involving local-luminance and local-contrast “gain control”, a “blob analysis” step to differentiate between cells, vessels and noise, and a method to exclude non-cell structures using specific combined ‘size’ and ‘aspect’ ratio criteria. Apoptosing retinal cells were counted by 3 masked operators, generating ‘Gold-standard’ mean manual cell counts, and were also counted using the newly developed automated algorithm. Comparison between automated cell counts and the mean manual cell counts on 66 DARC images showed significant correlation between the two methods (Pearson’s correlation coefficient 0.978 (p < 0.001), R Squared = 0.956. The Intraclass correlation coefficient was 0.986 (95% CI 0.977-0.991, p < 0.001), and Cronbach’s alpha measure of consistency = 0.986, confirming excellent correlation and consistency. No significant difference (p = 0.922, 95% CI: −5.53 to 6.10) was detected between the cell counts of the two methods.ConclusionsThe novel automated algorithm enabled accurate quantification of apoptosing RGCs that is highly comparable to manual counting, and appears to minimise operator-bias, whilst being both fast and reproducible. This may prove to be a valuable method of quantifying apoptosing retinal cells, with particular relevance to translation in the clinic, where a Phase I clinical trial of DARC in glaucoma patients is due to start shortly.

Elimination of Progressive Mammary Cancer by Repeated Administrations of Chimeric Antigen Receptor-Modified T Cells

Continuous oncogenic processes that generate cancer require an on-going treatment approach to eliminate the transformed cells, and prevent their further development. Here, we studied the ability of T cells expressing a chimeric antibody-based receptor (CAR) to offer a therapeutic benefit for breast cancer induced by erbB-2. We tested CAR-modified T cells (T-bodies) specific to erbB-2 for their antitumor potential in a mouse model overexpressing a human erbB-2 transgene that develops mammary tumors. Comparing the antitumor reactivity of CAR-modified T cells under various therapeutic settings, either prophylactic, prior to tumor development, or therapeutically. We found that repeated administration of CAR-modified T cells is required to eliminate spontaneously developing mammary cancer. Systemic, as well as intratumoral administered CAR-modified T cells accumulated at tumor sites and eventually eliminated the malignant cells. Interestingly, within a few weeks after a single CAR T cells' administration, and rejection of primary lesion, tumors usually relapsed both in treated mammary gland and at remote sites; however, repeated injections of CAR-modified T cells were able to control the secondary tumors. Since spontaneous tumors can arise repeatedly, especially in the case of syndromes characterized by specific susceptibility to cancer, multiple administrations of CAR-modified T cells can serve to control relapsing disease.

An easy way to make a good anti-tumor chimeric antigen receptor T cell?

The notion that the immune system has the capacity to prevent, control and eradicate cancer has been present for many years, but truly effective potent immunotherapeutic strategies have materialized only recently. One of the most successful and effective of these strategies involves adoptive transfer of genetically engineered T cells expressing chimeric antigen receptor (CAR) targeting the B-cell antigen CD19 present on B-cell lymphomas, acute lymphoblastic leukemia and chronic lymphocytic leukemia (1,2). Although the CD19 appears to represent an excellent safe target and the initial reports of efficacy are highly promising, it is clear that many aspects of the adoptive immunotherapy protocols still must be perfected. Generation of specific anti-tumor T cells in vitro requires their stimulation and significant expansion. The quality of the in vitroegenerated T-cell product appears to be as critical as the antigenic specificity of the T cells and can profoundly affect the treatment outcome. Traditionally, these highly cytotoxic, armed effectors were thought to be the most desirable by tumor immunologists because they displayed target killing capacity in vitro. Paradoxically, however, the in vivo function of these cells in animal models and in many clinical trials was disappointing (3). Gradually, it became clear that these armed terminal effectors displayed functional features of senescence and were unable to survive, expand and eradicate the tumor in vivo (4). In contrast, T cells under various conditions promoting less terminally differentiated central memory (CM) or even earlier stem cellelike phenotype display absent or low in vitro cytotoxic effector activity but much higher in vivo anti-tumor functionality that was

Human Amnion-Derived Cells: Prospects for the Treatment of Lung Diseases

Lung diseases represent a significant burden of morbidity and mortality worldwide. Current therapies have not proven adequate in the long term and are often associated with significant side effects. There has been recent interest in the regenerative/reparative potential of cell-based therapies, including cells derived from the placental tissues. Amnion-derived cells are fetal-derived and characterized by expression profile and differentiative capacity of pluripotent cells. Moreover, because placenta is discarded after delivery, they represent an ethical source for the purposes of regenerative medicine. Amnion-derived cells are endowed with immunomodulatory, anti-inflammatory, anti-scarring and antibacterial properties, which may explain many of the beneficial effects observed with administration of the cells in animal models for a large number of inflammatory diseases. Both human amniotic epithelial cells (hAEC) and mesenchymal stromal cells (hAMSC) have been shown to acquire in vitro and in vivo some characteristics of epithelial cells, i.e. CFTR (cystic fibrosis transmembrane conductance regulator) and surfactant proteins. Administration of hAEC or hAMSC in vivo in the bleomycin-induced lung injury model has proven their therapeutic effects in term of reduction of pulmonary fibrosis and inflammation, as well as recovery of lung mechanical function. Many biological and clinical information have to be gathered before proposing amnion-derived cells in the clinic for the treatment of acute and chronic lung diseases.

Flagellin pretreatment enhances the immunosuppressive capacity of mesenchymal stem cells in animal model of proctitis

Flagellin pretreatment enhances the immunosuppressive capacity of mesenchymal stem cells in animal model of proctitis