mesenchymal stem cell

Chronic wounds, a major clinical challenge, still need to develop new methods based on efficient technologies to improvetreatment results. Stem cells, particularly mesenchymal stem cells (MSC), as an advanced approach in skin regenerativemedicine, brought new hopes. The multifaceted effects of MSCs, including paracrine signaling, trophic factor secretion, andmodulation of the wound microenvironment, orchestrate a cascade of regenerative, plays a critical role in tissue repair. Preclinicalinvestigations have revealed the regenerative capacity of MSCs in accelerating wound closure, promoting angiogenesis, andfostering a pro-healing environment in chronic wound models. Clinical trials have also confirmed these findings and show theefficacy of MSC treatment in accelerating wound healing and improving the quality of healed tissue in patients with chronicwounds. Despite the therapeutic progress, key issues, such as optimal cell sourcing, cell dosage, delivery modalities, andlong-term safety profiles, there are a number of unresolved issues which need to be dealt with. This review aims to provide acomprehensive overview of current state of stem cell research in wound healing, and offers a new new hope for effective andinnovative treatments in regenerative medicine.

Intrauterine adhesions (IUAs), also known as Asherman syndrome, is a pathological condition characterized by the development of fibrous scar tissue within the uterine cavity, leading to menstrual abnormalities, infertility, and recurrent pregnancy loss. Current treatment options for IUAs are limited and often associated with suboptimal outcomes. In recent years, mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have emerged as potential therapeutic tools for various tissue injuries and disorders. MSCs play an important role in regeneration and repair and can differentiate into several lineages. These cells can be harvested from various sources, such as bone marrow, umbilical cord, adipose tissue, peripheral blood, and placenta. EVs are small membrane-bound vesicles containing a diverse cargo of proteins, lipids, and nucleic acids, which can be transferred to target cells to modulate their biological functions. Evidence suggests that EVs possess therapeutic properties similar to their parent cells but without the risks associated with cell-based therapies. Studies have demonstrated that EVs, by multiple pathways and mechanisms, can promote endometrial repair, reduce fibrosis, and restore normal uterine function in animal models of IUAs. Understanding the therapeutic effects of MSCs-derived EVs on IUAs could pave the way for developing novel and minimally invasive treatment options for this challenging condition. This review provides an overview of the current knowledge regarding the therapeutic potential of different sources of MSC-EVs in treating IUAs in preclinical and in vitro studies.

Sulfur mustard (SM) is an established chemical weapon that can result in severe damage to parts of the body. Currently, there are no effective treatments available for SM-caused damage.  We aimed to investigate the therapeutic potential of adipose-derived mesenchymal stromal cells (AD-MSCs) and conditioned medium (CM-MSCs) in acute and chronic pulmonary mouse models caused by 2-chloroethyl ethyl sulfide (CEES), an SM analog.
The mice were divided into 4 experimental groups:(1) CEES+AD-MSCs, (2) CEES+CM-MSCs, (3) CEES, and (4) control. The model observation time was divided into 7 days for the short and 6 months for the long term. AD-MSCs were injected into mice via intraperitoneal injection 24 hours after CEES exposure. The therapeutic effects of AD-MSCs on pulmonary tissue damage were assessed using histopathologic assay, measuring the neutrophil count, and bronchial alveolar lavage fluid (BALF) protein level. The levels of inflammatory and anti-inflammatory cytokines were evaluated using the enzyme-linked immunosorbent assay as the outcomes of interest.
Lung damage progression was reduced by AD-MSC treatment in mice after CEES injection into the peritoneum. The proportion of CD11b+F4/80+ macrophages in peritoneum was significantly lowered by AD-MSC treatment following CEES exposure. AD-MSC administration also reduced the level of pro-inflammatory cytokines, BALF protein, and nitric oxide levels in the peritoneal cavity.
By reducing inflammation and enhancing tissue healing, AD-MSCs and CM-MSC help prevent acute lung damage caused by CEES. The current study supports the use of a mouse model as a solid experimental foundation and indicates potential use for future cell treatment.

This study explored the synergistic effects of low-level laser therapy (LLLT) and adipose-derived stem cells (ADSCs) on cranial bone regeneration in rats, addressing the limitations of autogenous grafts and advancing bone tissue engineering with innovative photobiomodulation (PBM) applications.

Sixty Wistar rats were allocated to 5 separate groups randomly; (1) natural bovine bone mineral (NBBM); (2) NBBM + LLLT; (3) NBBM + allogenic ADSCs; (4) NBBM + allogenic ADSCs + LLLT; (5) Only defects. 8-mm calvarial defects were made in each rat in the surgical procedure. A diode laser was applied with the following parameters (continuous mode, power of 100mW, wavelength of 808nm, and 4 J/cm2 energy density) immediately after the procedure and every other day. Bone samples were obtained and assessed histomorphometrically and histologically after staining with hematoxylin and eosin (H&E).

Different volumes of bony material were observed in two weeks; 2.94% ± 1.00 in group 1, 5.1% ± 1.92 in group 2, 7.11% ± 2.82 in group 3, 7.34% ± 2.31 in group 4, and 2.01% ± 0.83 in group 5 (P < 0.05). On the other hand, foreign body residuals were up by 23% in the groups with scaffolding by the end of 2 weeks. Four weeks of observation led to 6.74 % ± 1.95, 13.24% ± 1.98, 15.76% ± 1.19, 15.92% ± 3.4, and 3.11% ± 1.00 bone formation in groups 1 to 5, respectively (P < 0.05). Generally, the difference between groups 2-4 was not statistically significant based on different types of bone and the extent of inflammation.

Bearing in mind the limitations of our research, it was demonstrated that ADSCs in combination with PBM have promising effects on bone tissue regeneration in sizeable bony defects. Furthermore, this study also showed that PBM usage improved the newly regenerated bone quality.

Liver diseases are a significant global health burden, causing roughly two million deaths annually. Liver Fibrosis, characterized by excessive extracellular matrix accumulation, is a major contributor to morbidity and mortality. Liver transplantation remains the gold standard for severe Fibrosis, but limitations exist. Cell therapy using Mesenchymal Stem Cells offers a promising alternative. Hepatocyte-like Cells derived from human adipose tissue Mesenchymal Stem Cells are particularly attractive due to their potential for liver regeneration. This study aimed to compare the effectiveness of Mesenchymal stem cells and Hepatocyte-like cells in treating CCl4-induced Liver Fibrosis in immunosuppressed mice.

Twenty C57BL/6 mice were divided into four groups: (1) control, (2) Fibrotic/untreated, (3 Mesenchymal stem cell-treated, (4) Hepatocyte-like cell-treated. Fibrosis was induced in groups 2-4 using intraperitoneal CCl4 injection in immunosuppressed (cyclosporine A) mice. Mesenchymal Stem Cells and Hepatocyte-like Cells were transplanted via tail vein injection in groups 3 and 4, respectively. Liver function tests were measured in all groups.

Both Mesenchymal Stem Cells and Hepatocyte-like Cells treatment improved liver function as evidenced by histopathology and biochemical analyses. In the Fibrotic group, Alanine aminotransferase, Aspartate aminotransferase, Alkaline phosphatase, and total bilirubin levels were significantly elevated, while Albumin levels decreased compared to the control group. Following treatment, these parameters significantly improved (p < 0.05) in both treatment groups, suggesting partial regression of Fibrosis.

Our findings suggest that both Hepatocyte-like Cells and Mesenchymal Stem Cells have therapeutic potential for moderating Liver Fibrosis regression. However, Mesenchymal Stem Cells therapy may be more cost-effective and time-efficient.

Radiation-induced peripheral neuropathy (RIPN) is one of the severe adverse effects of radiation therapy that significantly reduces patient quality of life. Bone marrow mesenchymal stem cells (BMSCs) exert beneficial effects on nerve regeneration following injury. We hypothesized that BMSCs are a potential treatment option for RIPN. This study aimed to evaluate the radioprotective effects of BMSCs on RIPN in a rat model.

The right sciatic nerves of fifty-four male Sprague-Dawley rats were locally irradiated with a single dose of 30 Gy X-rays. The rats were randomly divided into three groups (n = 18): Radiation control (RC), Radiation + BMSCs (RB) and Radiation + phosphate-buffered solution (RP). BMSCs and phosphate-buffered solution were administered via gastrocnemius muscle injection 24 hours after radiation exposure. Gait analysis, electrophysiological examinations and morphological examinations were performed subsequently.

No significant differences were observed between the RC and RP groups. Evaluation of the sciatic functional index demonstrated no statistical differences between the three groups after 4, 12 and 24 weeks. The RB group showed better improvement than either RC or RP group, as evidenced by increased motor nerve conductive velocity, expression level of S-100, mean diameter of the axon and thickness of the myelin sheath and decreased perineural scar tissue.

The present study indicated that BMSCs can improve the electrophysiological and morphological features of radiation exposed sciatic nerves, and have therapeutic potential for RIPN management.

Tissue engineering is a multidisciplinary and interdisciplinary topic that involves the development of biological implants for tissue regeneration intending to improve or enhance tissue or organ function.

This study aimed to evaluate the mechanical and histological properties of decellularized rat pancreas scaffolds, as well as to investigate the viability of adipose mesenchymal stem cells (MSCs) on the said scaffold for use in regenerative medicine and tissue engineering.

This is an experimental study that was performed in the research laboratory of Mohaghegh Ardabili University. To prepare the scaffold, male Wistar rats were anesthetized with carbon dioxide. After dissecting the mice, their pancreases were isolated and immediately transferred to a phosphate-buffered saline (PBS) solution to prepare them for decellularization. The decellularized scaffolds were evaluated histologically and mechanically. After decellularization, lipid MSCs were injected into de-cell scaffolds in the third passage.

Examination of the results of histological evaluations showed that scaffolding was completely decellularized. These results were confirmed by Mason trichrome and Dapi staining (coloring). Specialized tissue assessments by electron microscopy showed that the collagen and elastin strands were relatively conserved in the extracellular matrix (ECM).

In general, the result of this research demonstrates the successful decellularization of pancreatic tissue, effective preservation of the ECM of the desired tissue, and the viability of the MSCs on the scaffold resulting from the decellularization of the tissue.

Sulfur mustard (SM), an alkylating chemical agent, targets several organs, particularly the respiratory system, and results in early and late toxic effects. Currently, there is a considerable lack of adequate medical countermeasures for SM-associated lung injury. Mesenchymal stem cells (MSCs) are characterized by their self-renewal properties and differentiation capacity into multiple cell lineages. These features provide MSCs with the unique ability to engraft into injured tissues and exert immunomodulatory and tissue-repairing effects. Recent congruent findings on the usefulness of MSCs in the context of SM-induced pulmonary injury have raised the promise of their therapeutic use; however, their potential protective mechanisms are still unknown. A better understanding of the therapeutic mechanism of MSCs involved in SM-pulmonary injury would help figure out new target options. Accordingly, this study discusses the opportunities and therapeutic mechanisms of MSCs in SM poisoning. Recent advances in the treatment of SM-induced lung injury and the therapeutic mechanisms of MSCs as possible new treatments are highlighted. The PubMed and Scopus databases for published studies on the therapeutic approach of SM-induced lung manifestations were searched with a focus on the therapeutic mechanisms of MSCs.

Mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for rheumatoid arthritis (RA), but the current clinical results are varied. This study is to analyze the therapeutic effect of cell?based strategies on RA.

The searches were performed with public databases from inception to June 17, 2021. Randomized controlled trials researching cell?based therapies in RA patients were included.

Eight studies, including 480 patients, were included in the analysis. The results showed that compared to the control, MSC treatment significantly reduced the disease activity score (DAS) at the second standardized mean difference (SMD): ?0.70; 95% confidence interval (CI): ?1.25, ?0.15; P = 0.01) and 3rd month (SMD: ?1.47; 95% CI: ?2.77, ?0.18; P < 0.01) and significantly reduced the rheumatoid factor (RF) level at the first (SMD: ?0.38; 95% CI: ?0.72, ?0.05; P = 0.03) and 6th months (SMD: ?0.81; 95% CI: ?1.32, ?0.31; P < 0.01). In the network meta?analysis, MSCs combined with interferon?? (MSC_IFN) had a significant effect on increasing the American college of rheumatology criteria (ACR) 20, ACR50, and DAS <3.2 populations, had a significant effect on reducing the DAS, and decreased the RF level for a long period.

MSCs could relieve the DAS of RA patients in the short term and reduce the level of RF. MSC_IFN showed a more obvious effect, which could significantly improve the results of ACR20, ACR50, and DAS <3.2 and reduce the DAS and RF levels.

In this article published in Cell J, Vol 18, No 2, Jul-Sep (Summer) 2016, on pages 179-188, the authors found that Figure 2A was the same as the one that has already been published and it was confusing. The following figure’s legend is corrected in reference 9.
The authors would like to apologies for any inconvenience caused.

Brachial plexus injuries (BPI), although rare, often results in significant morbidity. Stem cell was thoughtto be one of BPI treatment modalities because of their nerve-forming regeneration potential. Although there is a possibility for the use of mesenchymal stem cells as one of BPI treatment, it is still limited on animal studies. Therefore, this systematic review aimed to analyze the role of mesenchymal stem cells in nerve regeneration in animal models of brachial plexus injury.

This study is a systematic review with PROSPERO registration number CRD4202128321. Literature searching was conducted using keywords experimental, animal, brachial plexus injury, mesenchymal stem cell implantation, clinical outcomes, electrophysiological outcomes, and histologic outcomes. Searches were performed in the PubMed, Scopus, and ScienceDirect databases. The risk of bias was assessed using SYRCLE's risk of bias tool for animal studies. The data obtained were described and in-depth analysis was performed.

Four studies were included in this study involving 183 animals from different species those are rats and rabbits. There was an increase in muscle weight and shortened initial onset time of muscle contraction in the group treated with stem cells. Electrophysiological results showed that mesenchymal stem cells exhibited higher (Compound muscle action potential) CMAP amplitude and shorter CMAP latency than control but not better than autograft. Histological outcomes showed an increase in axon density, axon number, and the formation of connections between nerve cells and target muscles.

Mesenchymal stem cell implantation to animals with brachial plexus injury showed its ability to regenerate nerve cells as evidenced by clinical, electrophysiological, and histopathological results. However, this systematic study involved experimental animals from various species so that the results cannot be uniformed, and conclusion should be drawn cautiously. Level of evidence: N/A

Mesenchymal Stem Cells (MSCs) can repair gastrointestinal tract damage. The Secretome of MSCs has a high capacity to inhibit bacterial colonization and the subsequent inflammatory responses of Vibrio cholerae.

The Caco-2 cells were treated with adipose-derived MSCs (AD-MSCs) secretome and then in- fected with V. cholerae. Subsequently, the bacterial attachment and invasion, cholera toxin gene expression, PGE2 and IL-6 secretion, TNF-α, IL-1β, and IL-8 expression, and apoptosis of Caco-2 cells were evaluated.

The secretome of AD-MSCs significantly reduced the V. cholerae attachment and internalization on Caco-2 epithe- lial cells (P<0.0001). The cholera toxin (Ctx-B) gene expression (FR=4.56 ± 0.66) and PGE2 production (P=0.0007) were also significantly reduced. The production of NO and TNF-α, IL-1β, and IL-8 pro-inflammatory cytokines were significantly (P<0.05) reduced in exposure to the secretome of AD-MSCs. Secretome also improved a significant 81.33% increase in IL-6 production (128.1 ± 37.6 pg/mL) and showed a 12.36% significant decrease in epithelial cell apoptosis (P< 0.0001) after exposure to V. cholerae.

The secretome of AD-MSCs can play a critical role in inhibiting bacterial colonization, and subsequent inflam- matory responses, and maintaining the integrity of the epithelial barrier. The secretome may be effective in the prevention of hypovolemic shock.

An individual with a genetic predisposition to inflammatory bowel disease (IBD) can experience inflammatory responses leading to conditions such as Crohn’s disease (CD) or Ulcerative colitis (UC). Currently, stem cell therapies, particularly those utilizing mesenchymal stem cells (MSCs), are gaining attention due to their immunomodulatory properties, as demonstrated in clinical trials. Consequently, we decided to investigate the effects of mesenchymal stem cells-conditioned medium (MSC-CM) and Abatacept in an experimental model of acute colitis. MSC-CM was extracted from female BALB/C mice and stored for future use. Acute colitis was induced in BALB/C mice through the intrarectal administration of 100 µL of 4% acetic acid. Following this procedure, CM and Abatacept were administered intraperitoneally. Throughout the study, various parameters were monitored, including changes in body weight, bleeding, stool consistency, disease activity index (DAI), mortality rate, as well as the weight and length of the colon. Histopathological analyses were also conducted, along with monitoring changes in the levels of IL-10 and IFN-γ. The data collected are presented as mean ± SD and were analyzed using One-Way ANOVA. According to the results of the study, CM with and without Abatacept significantly reduced weight loss and bleeding as well as improved fecal consistency and DAI. Macroscopic examination of the colon showed that after infusion, colon length was reduced and histopathological analysis showed a decrease in mucosal changes. The secretion of IL-10 was increased while the IFN-γ level was reduced. Research indicates that the immunomodulatory properties of MSC secretion can have positive effects. We propose a combination therapy with MSC, which we believe could lead to improved outcomes in the treatment of acute colitis.

Mesenchymal stem cells (MSCs) with their spindle like shapes are a lineage of stem cells with the capacity to self-renew and differentiate into osteoblasts, adipocytes, and chondrocytes and with CD105, CD73, and CD90 expression and the lack of CD34, CD14, CD45, and HLA-DR expression. The immunomodulatory, angiogenic, antiapoptotic, antimicrobial, and antioxidative characteristics of these cells made them more attractive in the field of cell-therapy for several autoimmune and inflammatory diseases, including diabetes, neurological disorders, sepsis, cardiac ischemia, and GvHD. For this reason, various protocols have been proposed to isolate mesenchymal stem cells from different tissue sources, such as adipose tissue (AT), umbilical cord (UC), Wharton’s jelly (WJ), bone marrow (BM), dental pulp, and even menstrual fluid. Considering the ease of access to the umbilical cord tissue and the fact that this tissue is rich in MSCs with embryonic origin and higher proliferation rate and lower senescence of the cells, the umbilical cord became a suitable source for explant MSC culture. In this study, we decided to introduce an explant culture protocol of MSCs that is less expensive and cost-effective achieving a high yield of MSCs.

 The main reason for treatment failure and the primary cause of breast cancer deaths is metastasis. Cancer features, such as epithelial to mesenchymal transition (EMT), invasiveness, stemness, and ability to metastasize, are significantly influenced by oxidative stress.

 The primary objective of this work was to evaluate the effects of human Wharton’s jelly mesenchymal stem cell secretomes (hWJMSCs-Se) on oxidant contents and development of the breast cancer SK-BR3 cell line and alterations in EMT markers genes after treatment.

 SK-BR3 cells received 48 hours of treatment with 10, 25, or 50 μg/mL hWJMSCs-Se. The MTT test and colony formation were used to evaluate the SK-BR3 cells’ viability and proliferation capability. By using annexin V/propidium iodide (PI) staining, apoptosis was determined. The messenger ribonucleic acid (mRNA) expression levels in genes associated with antioxidants were additionally assessed. Antioxidant enzyme activity was checked after SK-BR3 treatment with hWJMSCs-Se.

 In the hWJMSCs-Se-treated SK-BR3 cells, colony counts, and viability percentages decreased significantly with time and concentration. The treated cells displayed considerably greater apoptotic indices when compared to the control. Catalase (CAT), superoxide dismutase (SOD) activities, and glutathione (GSH) content were significantly greater in the hWJMSCs-Se-exposed SK-BR3 cells. The Vimentin gene and N-cadherin gene were significantly elevated in the treated cells, and E-cadherin and β-catenin decreased conversely.

 The present study suggests that the use of hWJMSCs in the treatment of human epidermal growth factor receptor 2 (HER2)-positive malignancies provides an innovative solution for cancer therapy. As the oxidant level and EMT pathway decreased, breast cancer cell growth was significantly restricted, and mortality increased.