Comparative assessment of proliferation and immunomodulatory potential of Hypericum perforatum plant and callus extracts on mesenchymal stem cells derived adipose tissue from multiple sclerosis patients

Background Mesenchymal stem cells-derived adipose tissue (AT-MSCs) are recognized for the treatment of inflammatory diseases including multiple sclerosis (MS). Hypericum perforatum (HP) is an anti-inflammatory pharmaceutical plant with bioactive compounds. Plant tissue culture is a technique to improve desired pharmacological potential. The aim of this study was to compare the anti-inflammatory and proliferative effects of callus with field-growing plant extracts of HP on AT-MSCs derived from MS patients. Materials and methods AT-MSCs were isolated and characterized. HP callus was prepared and exposure to light spectrum (blue, red, blue-red, and control). Total phenols, flavonoids, and hypericin of HP callus and plant extracts were measured. The effects of HP extracts concentrations on proliferation were evaluated by MTT assay. Co-culture of AT-MSCs: PBMCs were challenged by HP plant and callus extracts, and Tregs percentage was assessed by flow cytometry. Results Identification of MSCs was performed. Data showed that blue light could stimulate total phenols, flavonoids, and hypericin. MTT test demonstrated that plant extract in concentrations (0.03, 1.2, 2.5 and 10 mu g/ml) and HP callus extract in 10 mu g/ml significantly increased. Both HP extracts lead to an increase in Tregs percentage in all concentrations. In particular, a comparison between HP plant and callus extracts revealed that Tregs enhanced 3-fold more than control groups in the concentration of 10 mu g/ml callus. Conclusions High concentrations of HP extracts showed effectiveness on AT-MSCs proliferation and immunomodulatory properties with a certain consequence in callus extract. HP extracts may be considered as supplementary treatments for the patients who receiving MSCs transplantation

Various strategies to improve efficacy of stem cell transplantation in multiple sclerosis: Focus on mesenchymal stem cells and neuroprotection

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) which predominantly affect young adults and undergo heavy socioeconomic burdens. Conventional therapeutic modalities for MS mostly downregulate aggressive immune responses and are almost insufficient for management of progressive course of the disease. Mesenchymal stem cells (MSCs), due to both immunomodulatory and neuroprotective properties have been known as practical cells for treatment of neurodegenerative diseases like MS. However, clinical translation of MSCs is associated with some limitations such as short-life engraftment duration, little in vivo trans-differentiation and restricted accessibility into damaged sites. Therefore, laboratory manipulation of MSCs can improve efficacy of MSCs transplantation in MS patients. In this review, we discuss several novel approaches, which can potentially enhance MSCs capabilities for treating MS

Novel approaches using mesenchymal stem cells for curing peripheral nerve injuries

Peripheral nerve injury (PNI) is a common life-changing disability of peripheral nervous system with significant socioeconomic consequences. Conventional therapeutic approaches for PNI have several drawbacks such as need to autologous nerve scarifying, surplus surgery, and difficult accessibility to donor nerve; therefore, other therapeutic strategies such as mesenchymal stem cells (MSCs) therapy are getting more interesting. MSCs have been proved to be safe and efficient in numerous degenerative diseases of central and peripheral nervous systems. In this paper, we review novel biotechnological advancements in treating PNI using MSCs

Punica granatum peel supplementation attenuates cognitive deficits and brain injury in rat by targeting the Nrf2-HO-1 pathway

The critical role of nutrition to prevent neurodegenerative disorders is well documented. Punica granatum fruit is identified as a highly nutritional food for alleviating various ailments. The ameliorating properties of P. granatum peel on memory dysfunction and the possible roles of oxidative stress, acetylcholinesterase (AchE), and nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway in the scopolamine-treated rats were assessed. The hydroethanolic extract was standardized using high-performance liquid chromatography (HPLC). The animal groups were as follows: Control, scopolamine (2 mg/kg), and treatment groups (the extract at doses of 200–800 mg/kg). The behavioral performance was evaluated using the Morris water maze (MWM) and passive avoidance equipment. Various biochemical parameters were then measured. Rats received the extract properly found on the platform location, indicated by a shorter traveling time and distance during 5 days of learning MWM. Moreover, the extract increased the delay and light time, while decreasing dark time and the frequency of entries to the dark in the passive avoidance test. The extract also exerted a significant increase in superoxide dismutase activity and thiol content, while decreasing AchE activity and lipid peroxidation in the brain of scopolamine-injured rats. Our results demonstrated the neuroprotective effects of P. granatum peel in minimizing scopolamine injury possibly through targeting the Nrf2-HO-1 pathway

Mesenchymal stem cell-derived exosomes for managing graft-versus-host disease: An updated view

Graft-versus-host disease (GvHD) is the most common complication after stem cell transplantation, and also it is one of the primary limiting factors for the use of hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic cancers. GvHD, a systemic inflammatory disease, is caused by donor T cells recognizing the recipient's foreign antigens. In addition, an immune dysregulation, caused by autoreactive immune cells, complicates potent inflammatory process following HSCT. While there is no one approved treatment method for GvHD, corticosteroids are the most common first-line treatment. Exosomes are biological vesicles between 30 and 120 nm in diameter, which carry various biologically active molecules. They are known to play a key role in the paracrine effect of mesenchymal stem cells with therapeutic and tissue repair effects, including an immunosuppressive potential. Exosomes are unable to replicate themselves but because of their small size and fluid-like structure, they can pass through physiological barriers. Exosome are relatively easy to prepare and they can be quickly sterilized by a filtration process. Administration of exosomes, derived from mesenchymal stem cells, effectively reduced GvHD symptoms and significantly increased HSCT recipients' survival. Mesenchymal stem cell-derived exosome therapy reduced clinical symptoms of GvHD in patients after HSCT. Studies in patients with GvHD described that that mesenchymal stem cell-derived exosomes inhibited the release of IFN-γ and TNF-α by activated natural killer (NK cells), thereby reducing the lethal function of NK cells and inflammatory responses. Current review provides a comprehensive overview about the use of mesenchymal stem cells and their derived exosomes for the treatment of GvHD

Effects of 1,25-dihydroxyvitamin D3 on IL-17/IL-23 axis, IFN-γ and IL-4 expression in systemic lupus erythematosus induced mice model

Objective(s): Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease which may be characterized by T lymphocytes dysfunctions. Th17 cells have been identified as new effector cells, which play an important role in the pathogenesis. In recent years, immunomodulatory effect of vitamin D3 has been noticed. In the present experiment, the effect of vitamin D3 on the expression of IL-17, IL-23, IL-4 and IFN-γ were assessed in activated chromatin-induced mouse model for SLE. Materials and Methods: Five groups of mice were included in this study; Group one received active chromatin +CFA + PBS; Group 2 received vitamin D3  starting 2 weeks before disease induction; Group 3 received vitamin D3 (50 ng/day) starting with the disease establishment; Group 4 received non active chromatin +CFA + PBS; Group 5 received CFA + PBS. On day 56 splenocytes were isolated and gene expression of interleukin IL-17, IL-23, IL-4 and IFN-γ were analyzed by Real-Time PCR method. Proteinuria and serum anti-dsDNA and Th17 levels were measured using commercial kits. Results: The results showed that IL-17, IL-23, and IFN-γ mRNA expression, and IL-17 titers were decreased remarkably and that of IL-4 increased in mice which received vitamin D3 before SLE induction. Administration of vitamin D3 after the establishment of SLE failed to affect the IL-17 or IL-23 mRNA levels. Lastly, pre-treatment of mice with vitamin D3 decreased the anti-ds DNA antibody titer. Conclusion: Our findings showed that vitamin D3 supplementation in lupus induced mice through modulating the expression rate of some inflammatory cytokines diminished the inflammatory conditions in SLE

Immunoregulatory, proliferative and anti-oxidant effects of nanocurcuminoids on adipose-derived mesenchymal stem cells

Curcuminoids are dietary complexes extracted from the seeds of Curcuma longa L. that contain curcumin, bisdemethoxycurcumin and desmethoxycurcumin. Curcuminoids are popular for their pleiotropic therapeutic functions, such as their anti-inflammatory and anti-oxidant effects. Nonetheless, their clinical use is associated with poor systemic bioavailability and insolubility. The nano-formulation of curcuminoids eliminates these shortcomings. In the present study, we explored immunoregulatory, proliferative and anti-oxidant effects of nanocurcuminoids on adipose-derived mesenchymal stem cells (AT-MSCs). Flow cytometry analysis and MTT assay were employed to explore the effects of nanocurcuminoids on the apoptosis and proliferation of adipose-derived MSCs (AT-MSCs). The anti-oxidant effect of nanocurcuminoids on AT-MSCs also was examined. The immune regulatory effect of nanocurcuminoids was evaluated by the flow cytometric measurement of the T regulatory (Treg) population. The expression of inflammatory and anti-inflammatory cytokines was quantified using real-time PCR. Our findings demonstrate that low concentrations of nanocurcuminoids are beneficial for MSC proliferation, protection of MSCs from apoptosis, reducing inflammatory cytokines and SOD activity. A high concentration of nanocurcuminoids increases the population of Tregs and elevates the expression of TGFβ and FOXP3 genes. The beneficial effects of nanocurcuminoids on AT-MSCs were mainly observed at low doses of nanocurcuminoids

Evaluation of the immune-modulatory, anti-oxidant, proliferative, and anti-apoptotic effects of nano-silymarin on mesenchymal stem cells isolated from multiple sclerosis patients' adipose tissue sources

Silymarin (SL) has a long history of use for the treatment of a variety of diseases, but several limitations, such as poor bioavailability and negligible solubility, have restricted its successful translation in a clinical setting. However, the nano-micelle delivery system is a highly reproducible method which capable of improving poor-water solubility and bioavailability of free-SL. Mesenchymal stem cells (MSCs) are multipotent cells proficient in tissue renewal and regeneration. MSCs have similar properties to SL including immunomodulatory, antioxidant, and neuroprotective effects. Here, we show that nano-SL (1 and 2.5) increased AD-MSCs proliferation and protected from apoptosis. Our findings indicated that the levels of anti-inflammatory agents including IL-10, IL-4, FOXp3 and TGF-B mRNA expression were significantly upregulated in nano-SL-treated MSCs along with downregulated mRNA expression of pro-inflammatory cytokines (IL-6, IL-17). We identified that nano-SL elevated the T-regulatory (Treg) population (1 and 2.5 µM) and superoxide dismutase activity (2.5 µM) while decreasing nitrite oxide content. Conclusively, combinatorial therapy by nano-SL and MSCs may be useful for MS patients who are receiving MSCs for treatment

B lymphocytes in COVID-19: a tale of harmony and discordance

B lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection