mesenchymal stem cells

One of the leading causes of endometriosis is the return of menstrual blood flow into the pelvic cavity and the establishment of menstrual blood mesenchymal stem cells (MenSCs) outside the uterus. MenSCs from endometriosis patients (E-MenSCs) and healthy women have been shown to vary in terms of surface markers and gene expression, which may suggest the involvement of these cells in the development and expansion of ectopic lesions. This study aimed to investigate the effects of beta-catenin signaling inhibitor C-82 and naringenin as PI3K signaling pathway inhibitors on E-MenSCs to modulate their gene expression and functional pattern. 

Briefly, E-MenSCs isolated by density-gradient centrifugation were treated with C-82 and naringenin, and the genes and pathways related to inflammation, proliferation, and survival were evaluated. E-MenSCs showed increased early apoptosis and decreased levels of ROS, IL-6 and IL-8, ER, α-SMA, and Ki-67 protein expression. 

Our results shed light on the function of C-82 and naringenin in modulating E-MenSCs. 

However, more research is needed to analyze the precise effects of small molecule C-82 and naringenin on endometriosis.

Due to the scarcity of treatment options, managing the progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to cirrhosis necessitates innovative approaches. This study focused on endoplasmic reticulum (ER) stress, apoptosis, and autophagy as key mechanisms in NAFLD pathogenesis. It also highlighted the potential of adipose-derived mesenchymal stem cells (AD-MSCs) and their exosomes as promising therapeutic options. The study was conducted at the Department of Regenerative Medicine, Shiraz University of Medical Sciences, (Shiraz, Iran) from November 2021 to December 2023. The mice (n=32) were divided into four groups: control, high-fat diet (HFD) without treatment, HFD with AD-MSCs treatment, and HFD with AD-MSCs-derived exosomes groups. The mice were fed HFD for 8 weeks. They received MSC and exosomes for the last 3 weeks. One week after the final injection, mice were tested for serum testing, stereological analysis, and real-time polymerase chain reaction (RT-PCR). The data were analyzed using the Graph-Pad Prism software by one-way analysis of variance (ANOVA) with Tukey analysis as a post hoc comparison between groups. P<0.05 indicated a significant difference.  AD-MSCs-exosomes significantly reduced ER stress indicators (IRE1α [P=0.0001], PERK [P=0.0006], ATF6 [P=0.0001], and GRP78 [P=0.0001]), apoptosis markers (Bax [P=0.005] and Cas3 [P=0.001]), and autophagic flux markers (P62 [P=0.0001] and LC3B/A [P=0.003]).  In this investigation, AD-MSCs-exosomes significantly restored autophagy and suppressed unfolded protein response (UPR) pathways in the early stages of NAFLD.

To date, different strategies have been used for co-transplantation of cell-loaded biomaterials for bone tissue regeneration. This study aimed to investigate the osteogenic properties of adipose-derived-mesenchymal stem cell (AD-MSC) sheets combined with nanofibrous poly-caprolactone (PCL) mat and Gelfoam in rats with calvarial bone defect.

Calvarial critical-size defects were induced in male rats. Animals were classified into Control, Gelfoam, Gelfoam/PCL nanofiber, Gelfoam/AD-MSC sheet, and Gelfoam/PCL nanofiber/AD-MSC sheet groups. After 3 months, rats were sacrificed and the regeneration rate was evaluated.

Almost all groups showed bone regeneration properties, but the volume of newly formed bone was higher in groups that received Gelfoam/AD-MSC and Gelfoam/PCL nanofiber/AD-MSC sheets (P < 0.05). The application of Gelfoam/PCL nanofiber/AD-MSC sheets not only increased bone thickness, bone volume/total bone volume (BV/TV) ratio, strong Hounsfield Unit (HU), but also led to the formation of ossified connective tissue with wrinkled patterns.

The current study indicated that the Gelfoam/PCL nanofiber/AD-MSC sheet provides a suitable platform for effective osteogenesis in calvarial bone defects.

Neuropathic pain, a chronic condition resulting from somatosensory system damage, remains a significant clinical challenge due to its complex pathophysiology and inadequate response to traditional therapies. Oxidative stress, characterized by an imbalance between free radicals production and antioxidant defenses, plays a pivotal role in the development and maintenance of neuropathic pain. Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to differentiate into various cell types and possess immunomodulatory, anti-inflammatory, and regenerative properties, making them promising candidates for novel pain management strategies. Preclinical studies demonstrate that MSCs can reduce inflammation, scavenge reactive oxygen species (ROS), promote nerve regeneration, and modulate pain signaling pathways. Various administration routes, including intravenous and intrathecal, have been investigated to optimize MSC delivery and efficacy. Additionally, MSC-derived extracellular vesicles (EVs) represent a cell-free alternative with substantial therapeutic potential. Despite encouraging preclinical findings, further research is needed to refine MSC-based therapies, including the exploration of combination treatments and rigorous clinical trials, to translate these promising results into effective clinical applications for neuropathic pain relief. This review explores the therapeutic potential of MSCs in alleviating oxidative stress-mediated neuropathic pain.

Mesenchymal stem cells of human umbilical cord origin (hucMSCs) appear to be an attractive candidate for cell-based therapies. However, their efficacy requires improvement as poor survival and specific homing to the site of injury are the major barriers to their effective implementation in cell therapy. As Wnt signaling pathway is involved in the development and repair of organs, we adopted a preconditioning strategy of stem cells by using CHIR99021 compound (a Wnt pathway agonist) to potentiate hucMSCs beneficial effects and circumvent their therapeutic limitations.

We treated hucMSCs with 5 µM of CHIR99021 and evaluated the expression levels of genes involved in different biological processes through qRT-PCR. Subsequently, we examined the effectiveness of preconditioned cells (CHIR99021-hucMSCs) in a cisplatin-induced rat acute kidney injury model. Amelioration in tissue injury was evaluated by histopathology, immunohistochemistry and renal functional assessment.

In treated groups, we observed preserved renal tissue architecture in terms of lesser epithelial cells necrosis (P ≤ 0.001) and cast formation ( ≤ 0.05). Accelerated proliferation of injured tubular cells (P ≤ 0.001) and low serum creatinine values (P ≤ 0.01) were observed in preconditioned hucMSCs group compared to untreated AKI rats. In addition, administration of preconditioned hucMSCs in kidney injury model offered better restoration of tubular cell membrane β-catenin molecules. Our findings showed that CHIR99021-modified hucMSCs may exhibit better capacity for cell migration and proliferation.

The results showed that preconditioning of stem cells with Wnt pathway activators could provide advanced benefits for organ repair, which may contribute to design a more effective therapeutic approach for renal regeneration.

In the article published in Cell J, Vol 15, No 4, 2015, pages 364-371, the reference for Table 1 and Figures 1B-D, 2,and 5A, B was inadvertently omitted. The missing reference (24), originally written in Persian by the authors, has nowbeen added to the relevant Table and Figures' legends with the permission of the original publisher, Journal of ArdabilUniversity of Medical Sciences.The authors would like to apologies for any inconvenience caused.

Reducing the immune response to inflammation is vital for successful transplantation, yet chronic graft rejection remains a major issue despite immunosuppressive drugs. This study explored the effect of bone marrow mesenchymal stem cell-derived exosomes on the survival of skin allografts in mice.

C57BL/6 and BALB/c mice underwent skin allograft surgery, followed by intraperitoneal injection of exosomes, which were compared with groups receiving dexamethasone and no treatment group.

On day 3, mild signs of graft rejection appeared in both control groups, while none were seen in the exosome-treated group. By day 14, the grafts were completely rejected in the control groups but showed mild rejection in the treatment group. Histopathology revealed severe rejection signs in the control groups, including epithelial necrosis and inflammation, while the treatment group showed signs of angiogenesis and graft acceptance. Additionally, inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were lower in the treatment group than in the positive control group, particularly on days 3 and 14.

The findings suggest that exosomes can prevent graft rejection and may offer a promising therapeutic approach for solid organ transplantation, though further research is needed to standardize exosome methods and evaluate cost-effectiveness.

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive destruction of behavioral and cognitive functions. Various therapies have been tested to improve or at least effectively change the course of AD. In recent years; stem cell therapy has emerged as a hopeful potential treatment for Alzheimer's. Stem cells can differentiate into various types of cells, including brain cells, potentially replacing damaged cells and improving cognitive function.

In the present study we investigated the inhibitory effect of mesenchymal stem cells isolated from amniotic membrane (AM-MSCs) on neural progenitor cells (NPC) treated with Scopolamine.

NPC cell was provided by the Iranian Biological Resource Center. To expose these cells to Alzheimer's situations, scopolamine (0.05 mg/ml) treatment has been used. The inhibitory effect of mesenchymal stem cells isolated from the amniotic membrane was evaluated by using the co-cultivation method. The expression of amyloid beta (Aβ), TERM2, Tau, and ABCA7 genes, was assessed in NPC cells co-cultivated with AM-MSC by Real-time PCR. After the Co-culture of AM-MSC and NPC cells for 72 hours, we evaluated the expression of BDNF and CHAT protein in Co-cultured NPC cells by immunocytochemical test.

Results of Real-time PCR and Immunocytochemistry showed that in Co-culture of AM-MSC with NPC decreased Aß, TREM2, and Tau gene expression and increased ABCA7 expression. As well, the expression of BDNF and CHAT protein enhanced.

AM-MSCs have attracted much consideration. MSCs have the capability of immune regulation, regeneration, and neuroprotection These cells are a potential candidate for cell therapy due to their easy accessibility and compliance with ethical issues.

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive destruction of behavioral and cognitive functions. Various therapies have been tested to improve or at least effectively change the course of AD. In recent years; stem cell therapy has emerged as a hopeful potential treatment for Alzheimer's. Stem cells can differentiate into various types of cells, including brain cells, potentially replacing damaged cells and improving cognitive function.

In the present study we investigated the inhibitory effect of mesenchymal stem cells isolated from amniotic membrane (AM-MSCs) on neural progenitor cells (NPC) treated with Scopolamine.

NPC cell was provided by the Iranian Biological Resource Center. To expose these cells to Alzheimer's situations, scopolamine (0.05 mg/ml) treatment has been used. The inhibitory effect of mesenchymal stem cells isolated from the amniotic membrane was evaluated by using the co-cultivation method. The expression of amyloid beta (Aβ), TERM2, Tau, and ABCA7 genes, was assessed in NPC cells co-cultivated with AM-MSC by Real-time PCR. After the Co-culture of AM-MSC and NPC cells for 72 hours, we evaluated the expression of BDNF and CHAT protein in Co-cultured NPC cells by immunocytochemical test.

Results of Real-time PCR and Immunocytochemistry showed that in Co-culture of AM-MSC with NPC decreased Aß, TREM2, and Tau gene expression and increased ABCA7 expression. As well, the expression of BDNF and CHAT protein enhanced.

AM-MSCs have attracted much consideration. MSCs have the capability of immune regulation, regeneration, and neuroprotection These cells are a potential candidate for cell therapy due to their easy accessibility and compliance with ethical issues.

Ultraviolet B (UVB) irradiation induces photoaging and apoptosis in various cell types. Inhibition of UVB-induced apoptotic pathways has been explored in different apoptotic cascades. Conditioned media from human umbilical cord blood mesenchymal stem cells (CM-hUCB-MSC) contain important substances for cell regeneration. However, the potential of CM-hUCB-MSC in preventing UVB-induced apoptosis has not been clearly elucidated. Therefore, the current research was conducted to investigate the potential of CM-hUCB-MSC in inhibiting UVB-induced apoptosis and its role in the antiapoptotic signaling pathway. An experimental in vitro study was conducted at PT. Prodia StemCell Indonesia, Jakarta, Indonesia, 2019-2022. Initially, hUCB-MSCs were isolated and cultured to produce CM-hUCB-MSC. NIH3T3 cells were pretreated with/without 50 μM LY294002, treated with/without 10% CM-hUCB-MSC, and then irradiated with/without UVB. Subsequently, the cells were analyzed using sub-G1, immunofluorescence, and immunoblotting assays. One-way analysis of variance (ANOVA) was used for data analysis, followed by Tukey’s honest significant difference (HSD) test or the Kruskal-Wallis test, followed by the Dunn-Bonferroni test using IBM SPSS Statistics software version 21. Statistical significance was determined at P<0.05. CM-hUCB-MSC significantly inhibited UVB-induced apoptosis in NIH3T3 cells (P=0.002, Dunn-Bonferroni test). CM-hUCB-MSC significantly induced Akt phosphorylation at Ser 473 in UVB-irradiated NIH3T3 cells (P<0.001, Tukey’s HSD test). The CM-hUCB-MSC-induced phosphorylation of Akt was significantly inhibited by LY294002 (P<0.001, Tukey’s HSD test). Taken together, it can be concluded that CM-hUCB-MSC inhibits UVB-induced NIH3T3 cell apoptosis via the activation of phosphatidylinositol-3-kinase (PI3K)/Akt signaling cascades.

The dental pulp is essential for tooth health and sensory function. However, conventional treatments for infected or necrotic pulp, such as root canal therapy, frequently result in tooth loss and increased fracture risk. Regenerative endodontic procedures (REPs) aim to regenerate pulp tissue while preserving tooth vitality. Exosomes from human umbilical cord mesenchymal stromal/stem cells (hUCMSCs) demonstrated potential for tissue regeneration. In this case report, the potential of hUCMSC-derived exosomes for regenerating the dental pulp of a pulpectomized tooth was investigated. The patient, a 40-year-old man, was presented with irreversible pulpitis in the mandibular second premolar. The patient underwent a pulpectomy, followed by the application of a chitosan and hUCMSC-derived exosome mixture into the root canal. This project was conceived and executed as a joint project in Bushehr (Iran), Shiraz (Iran), and Aktobe (Kazakhstan) from 2022 to 2024. Exosomes were isolated and characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Clinical evaluations, including visual inspection, palpation, pulp vitality tests, radiography, and cone beam computed tomography (CBCT) imaging, were conducted over 24 weeks post-treatment. The SEM and TEM images confirmed the effective isolation and characterization of exosomes. Clinical follow-ups showed no signs of infection, swelling, or tenderness around the treated tooth. Radiographic assessments indicated periapical radiolucency and periodontal ligament widening, suggesting active healing. Despite these radiographic changes, the absence of clinical symptoms indicated successful tissue regeneration and integration. This case report demonstrated the potential of hUCMSC-derived exosomes for dental pulp regeneration, with promising results in maintaining tooth vitality and promoting healing.

Allergic asthma is a chronic inflammatory disease characterized by airway remodeling, hyperresponsiveness, and exacerbated inflammation. While most patients respond well to current treatments, a small subset remains resistant necessitating new therapeutic strategies. Due to their immunomodulatory properties, stem cells have been proposed as a promising treatment option for asthma. Stem cells can reduce airway inflammation and restore immune balance, demonstrating positive outcomes, particularly in cases of steroid-resistant asthma. However, the mechanisms underlying lung tissue repair are not clearly defined. On the other hand, there are limitations in using these cells and for clinical use of mesenchymal stem cells, which must be produced in accordance with Good Manufacturing Practice. This review article discusses the mechanisms by which stem cells may aid in asthma treatment and addresses and explores the challenges associated with their use. By addressing these areas, we can better understand the potential and limitations of stem cell therapy in asthma and develop more effective strategies to harness their therapeutic benefits for patients with uncontrolled asthma.

Heart failure (HF) is a prevalent diagnosis with a significant mortality rate. Various therapeutic approaches exist for treating HF, and human adipose-derived mesenchymal stem cells-conditioned medium (hAMSCs-CM) therapy has emerged as a promising option. Despite its potential efficacy, the precise mechanism of action underlying hAMSCs-CM treatment remains unclear. To address this knowledge gap, we conducted a novel animal study to investigate the mechanism of action of hAMSCs-CM in an HF model, with a specific focus on transforming growth factor-β (TGF-β)/galectin-3, monocyte chemoattractant protein-1 (MCP1), B-type natriuretic peptide (BNP), and aldosterone (ALD).

Forty adult male Wistar rats were divided into 4 groups: control, HF, culture medium, and CM. All rats, except those in the control group, received an injection of isoproterenol to induce an animal model of HF. The CM group was administered the CM, while those in the culture medium group received standard culture media. Subsequently, serum levels of fibrotic factors, including TGF-β/galectin-3, MCP1, BNP, and ALD, were measured using ELISA. Statistical analysis was performed using one-way analysis of variance and the Tukey test.

Serum levels of TGF-β/galectin-3, MCP1, BNP, and ALD were significantly elevated in the HF, CM, and culture medium groups compared with the control group (P<0.001). Additionally, these fibrotic factors were significantly reduced in the CM group compared with the HF group (P<0.001). Notably, CM therapy could not restore TGF-β/galectin-3, MCP1, BNP, or ALD levels to the normal range observed in the control group.

 Our findings indicate that hAMSCs-CM modulates the expression of inflammatory and fibrotic cytokines, such as TGF-β/galectin-3, MCP1, BNP, and ALD, in isoproterenol-induced HF in male rats. These results contribute to a better understanding of the therapeutic mechanisms underlying hAMSCs-CM treatment for HF.

This study aimed to construct a decellularized mouse spleen scaffold and evaluate its cellular compatibility in vitro using murine bone marrow-derived mesenchymal stem cells (BM-MSCs).

A combination of physical, chemical, and enzymatic treatments was employed for mouse spleen decellularization. These included multiple freeze-thaw cycles, the ionic detergent sodium dodecyl sulfate (SDS), and enzymatic trypsin. Histological and scanning electron microscopy analyses were conducted up to 7 days post-culture to assess the impact of decellularization and cellular adaptation to the spleen scaffolds.

Histological studies revealed the attachment and penetration of BM-MSCs into the scaffolds on days 5-7 following cell seeding. Furthermore, cell migration into the scaffold was observed 5 days after the seeding process.

The decellularization approach utilized in this study proved to be effective and biocompatible, supporting the preservation and proliferation of BM-MSCs. These findings indicate its potential for spleen tissue engineering applications.

Cancer, as a complicated disease, is considered to be one of the major leading causes of death globally. Although various cancer therapeutic strategies have been established, however, some issues confine the efficacies of the treatments. In recent decades researchers for finding efficient therapeutic solutions have extensively focused on the abilities of stem cells in cancer inhibition. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can the most widely extracted from various sources such as the bone marrow (BM), placenta, umbilical cord (UC), menses blood, Wharton’s jelly (WJ), adipose tissue and dental pulp (DP). These cells are capable of differentiating into the osteoblasts, chondrocytes, and adipocytes. Due to the unique characteristics of MSCs such as paracrine effects, immunomodulation, tumor-tropism, and migration, they are considered promising candidates for cancer therapeutics. Currently, MSCs are an excellent living carrier for delivery of therapeutic genes and chemical agents to target tumor sites. Also, exosomes, the most important extracellular vesicle released from MSCs, act as a strong cell-free tool for cancer therapeutics. MSCs can prevent cancer progression by inhibiting several signaling pathways, such as wnt/β-catenin and PI3K/AKT/mTOR. However, there are several challenges associated with the use of MSCs and their exosomes in the field of therapy that need to be considered. This review explores the significance of MSCs in cell-based therapy, focusing on their homing properties and immunomodulatory characteristics. It also examines the potential of using MSCs as carriers for delivery of anticancer agents and their role in modulating the signal transduction pathways of cancer cells.

Lung is one of the vital organs that get severely affected by cytokine storm and sepsis, leading to the development of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Mesenchymal stem cell- derived small extracellular vesicles (MSC- derived sEVs) are one of the therapeutic approaches for ARDS/ ALI caused by sepsis. Apart from sEVs’ ability to carry medication, MSC- derived sEVs also possess anti- inflammatory, tissue repair, and regeneration properties. Targeted drug delivery has been a crucial area of concern in the medical field, specifically for treating lung diseases. To treat lung diseases locally, inhalation of drug products has been developed. Drug delivery by inhalation has emerged as an effective method for local administration of therapeutic agents, with numerous benefits including better efficacy at lower doses and decreased toxicity. Additionally, inhalation administration is a viable option for the systemic distribution of medications due to the lungs' considerable absorption surface and their ability to bypass initial metabolism. Therefore, our hypothesis proposes the inhalation of MSC- derived sEVs as a potential strategy for alleviating acute lung injury induced by sepsis-related cytokine storm. Following the isolation and characterization of these MSC- derived sEVs, they will be administered to an animal model of sepsis via a nebulizer, either in their pure form or loaded with drugs. Several approaches will be employed to evaluate lung functionality, including histological analysis and the measurement of inflammatory and regulatory cytokine levels to assess changes in both the humoral and cellular immune systems

Atrophy of the muscles following denervation can lead to the death of myofibers. This study evaluated the sciatic nerve and tibialis cranialis muscle (TCM) regeneration using scaffold and cells. 

Ninety adult male Wistar rats were divided into six main groups (n=15) and three subgroups (2, 4, and 8 weeks). Groups: control; without surgery, Tr; sciatic nerve transected in silicone tube, S; collagen gel put inside the silicone tube, MC; placed 3×104 mast cells mixed with scaffold, MSC; placed 3×104 mesenchymal stem cells mixed with scaffold, and MC+MSC; 3×104 of each of the mast cell and mesenchymal stem cells along with scaffold. Animals were euthanized and sampled for muscle and nerve histological and nerve immunohistochemical evaluations. 

Diameter of muscle fibers, ratio of the muscle fiber’s nuclei to the fibrocyte nuclei (mn/fn), ratio of the muscle fibers nuclei number to the muscle fiber’s number (mn/mf), and ratio of the blood vessels number to the number of muscle fibers (v/mf) in all treatment groups, especially the MC + MSC group, increased compared to the Tr group but the number of mast cells, the percentage of sarcoplasmolysis, and necrosis fibers decreased. Histomorphometric results of the nerve in its various parts and immunohistochemistry results also showed improved nerve conduction, especially in the MC + MSC group. 

In this study, nerve improvement happened mainly for two reasons: cells and time. So, the most obvious improvement occurred in the group with mast and mesenchymal cells in the 8th week.