Source Of Mesenchymal Stem Cells Research Articles

Lidocaine intensifies the anti-osteogenic effect on inflammation-induced human dental pulp stem cells via mitogen-activated protein kinase inhibition

Human dental pulp stem cells (hDPSCs) are an emerging source of mesenchymal stem cells (MSCs) for bone tissue regeneration and engineering. In bone regeneration using transplanted MSCs, the extracellular environment or co-injected drugs can affect their success or failure. In this study, we investigated the effects and signaling mechanisms of lidocaine on osteogenic differentiation of hDPSCs after inducing inflammatory conditions with lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α). To investigate the effect of lidocaine on the osteogenic differentiation of LPS/TNF-α-treated hDPSCs, alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were conducted. The expression of osteogenesis-related genes was assessed using quantitative real-time polymerase chain reaction and western blotting. The expression of mitogen-activated protein kinases was analyzed to evaluate the effect of lidocaine on osteogenic differentiation of LPS/TNF-α-treated hDPSCs. Various concentrations of lidocaine (0.05, 0.2, and 1mM) further decreased ALP and ARS staining of LPS/TNF-α-treated hDPSCs. Similarly, the mRNA and protein expression of osteogenesis-related genes was suppressed via lidocaine treatment in LPS/TNF-α-treated hDPSCs. Lidocaine treatment downregulated the protein expression of p-ERK and p-JNK in LPS/TNF-α-treated hDPSCs. Lidocaine intensified the inhibition of osteogenic differentiation on inflammation-induced hDPSCs by inhibiting the ERK and JNK signaling pathways. This invitro study suggested that lidocaine may have an inhibitory effect on bone regeneration.

Simple Procedure for the Isolation of Mesenchymal Stem Cells from Different Parts of the Human Umbilical Cord

The umbilical cord and placenta are both sources of mesenchymal stem cells (MSCs) that are promising for cell-based therapy. Furthermore, compared to other MSCs sources, they are easy to obtain with no invasive procedures. This study presents an adapted method for stem cell isolation from three different parts of the human umbilical cord, including Wharton’s jelly (WJ), cord lining (CL), and cord-placenta junction (CPJ). The isolation consists of sample preparation, tissue dissection into distinct anatomical regions, mincing and enzyme digestion, and explant culturing. In addition, we monitored when the cells migrated from the explant to the bottom of the cell culture dish and passed the cells after they became confluent. This study found that WJ cells were the first to reach confluence at Passage 0 (P0). In contrast, CL cells needed the longest time to get confluence at P0 but displayed faster cell growth after subsequent passages (P1-P2). In addition, CPJ cells showed growth retardation after P1 and P2. Altogether, we could extract the MSCs from umbilical cord tissue explants by using DMEM supplemented with 10% FBS, 100 IU/mL penicillin, and 100 μg/mL streptomycin as general cell culture medium and omitting the use of gentamicin. However, the MSCs may need a more complex specified medium for optimum cell regeneration for further cell expansion.Keywords: mesenchymal stem cells, umbilical cord, Wharton’s jelly, cord lining, cord-placenta junction.

Biologics, Stem Cells, Growth Factors, Platelet-Rich Plasma, Hemarthrosis, and Scaffolds May Enhance Anterior Cruciate Ligament Surgical Treatment

AbstractBiologics including mesenchymal stem cells (MSCs), growth factors, and platelet-rich plasma may enhance anterior cruciate ligament (ACL) reconstruction and even ACL primary repair. In addition, hemarthrosis after acute ACL injury represents a source of biologic factors. MSCs can differentiate into both fibroblasts and osteoblasts, potentially providing a transition between the ligament or graft and bone. MSCs also produce cytokines and growth factors necessary for cartilage, bone, ligament, and tendon regeneration. MSC sources including bone marrow, synovium, adipose tissue, ACL-remnant, patellar tendon, and umbilical cord. Also, scaffolds may represent a tool for ACL tissue engineering. A scaffold should be porous, which allows cell growth and flow of nutrients and waste, should be biocompatible, and might have mechanical properties that match the native ACL. Scaffolds have the potential to deliver bioactive molecules or stem cells. Synthetic and biologically derived scaffolds are widely available. ACL reconstruction with improved outcome, ACL repair, and ACL tissue engineering are promising goals. Level of EvidenceLevel V, expert opinion.

Safety and Efficacy of Mesenchymal Stem Cells in Burn Therapy: Systematic Review

The experimental research on the use of mesenchymal stem cells (MSCs) for burn therapy has been published several times. However, current clinical procedure remains a challenging discussion. This systematic review assesses the safety and efficacy of administering mesenchymal stem cells (MSCs) to burns and determines the most effective source of MSCs for burn therapy. We reviewed several studies through PubMed, Google Scholar, Science Direct, and DOAJ online databases. PRISMA-P 2020 method was used based on inclusion and exclusion criteria that were re-selected through Joanna Briggs Institute (JBI) Critical Appraisal Tools. Results from 13 articles showed that MSCs are safe for burn therapy with minimal side effects/complications and have the potential to repair tissue and accelerate burn healing through several mechanisms. The treatment of MSCs in burns is influenced by donor characteristics and related to the severity and area of the burn. It can be concluded that the administration of MSCs is safe and effective in burn therapy. Keywords: burns, mesenchymal stem cells, therapeutic safety, therapeutic efficacy, wound healing

Mesenchymal Stem Cell Therapy for Acetaminophen-related Liver Injury: A Systematic Review and Meta-analysis of Experimental Studies In Vivo.

The efficacy of mesenchymal stem cell (MSC) therapy in acetaminophen-induced liver injury has been investigated in animal experiments, but individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis of preclinical studies to explore the potential of using MSCs in acetaminophen- induced liver injury. Eight databases were searched for studies reporting the effects of MSCs on acetaminophen hepatoxicity. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. SYRCLE's risk of bias tool for animal studies was applied to assess the methodological quality. A meta-analysis was performed by using RevMan 5.4 and STATA/ SE 16.0 software. Eleven studies involving 159 animals were included according to PRISMA statement guidelines. Significant associations were found for MSCs with the levels of alanine transaminase (ALT) (standardized mean difference (SMD) - 2.58, p < 0.0001), aspartate aminotransferase (AST) (SMD - 1.75, p = 0.001), glutathione (GSH) (SMD 3.7, p < 0.0001), superoxide dismutase (SOD) (SMD 1.86, p = 0.022), interleukin 10 (IL-10) (SMD 5.14, p = 0.0002) and tumor necrosis factor-α (TNF-α) (SMD - 4.48, p = 0.011) compared with those in the control group. The subgroup analysis showed that the tissue source of MSCs significantly affected the therapeutic efficacy (p < 0.05). Our meta-analysis results demonstrate that MSCs could be a potential treatment for acetaminophen- related liver injury. The protocol for this meta-analysis was prospectively registered in PROSPERO (Number: CRD42020212677).

Low Oxygen Tension Inhibits Senescence in Bone Marrow Mesenchymal Stem Cells (BMSCs)

Background: Stem cells have been used in regenerative medicine but are so few in the body that they require cell culture. Stem cell culture was performed under normal oxygen tension and passage was carried out until the number of cells was sufficient for therapy. Stem cell cultures under normal oxygen tension do not match the stem cell microenvironment, which can lead to premature senescence. This study aims to determine the association of low oxygen tension with premature senescence of mesenchymal stem cells (MSCs) through inhibition of p21 expression by HIF-1a. Methode: The research method used rabbit bone marrow in New Zealand as a source of MSCs. The results of isolation of MSCs were divided into two groups for cultured on normal and low oxygen tension until 10 passages. Cells were identified using flowcytometry for cd105 and cd34. At early and late passage, the expression of p21 and HIF-1a was examined using immunofluorescence while senescence was examined using β-galactosidase assay. Results: The results showed that in low oxygen cultures HIF-1a expression increased significantly (p &lt;0.05) while p21 expression decreased significantly (p &lt;0.05) as did the β-galactosidase assay. Conclusions: The conclusion of this research is low oxygen tension culture able to decrease premature senescence culture of invitro stem cells mesenchymal through obstacles p21 by HIF-1a.&#x0D; Keywords: p21 expression, HIF-1a expression, late passage, premature senescence.

Umbilical Cord-Derived Mesenchymal Stem Cells for the Treatment of Infertility Due to Premature Ovarian Failure.

Females belonging to the reproductive age group may face challenges regarding infertility or miscarriage due to conditions such as premature ovarian failure (POF). It is the conditionthat happens when a female's ovaries stop working before she is 40. The majority of the causes of POF cases are idiopathic. Other reasons includegenetic disorders (Turner's syndrome, bone morphogenetic protein 15 (BMP15) mutation, galactosemia, mutation of forkhead box protein L2 (FOXL2), growth differentiation factor-9 (GDF9), mutation of luteinizing hormone (LH) and follicle-stimulating hormonereceptors (FSHR), etc.), enzymatic mutation such as aromatase, autoimmune disorders (Addison's disease, vitiligo, systemic lupus erythematosus, myasthenia gravis, autoimmune thyroiditis, autoimmune polyglandular syndrome, etc.), vaccination, and environmental factors (cigarette smoking, toxins, and infections). Manyattempts have been made to treat POF by various methods. Some of the methods of treatment include hormone replacement therapy (HRT), melatonin therapy, dehydroepiandrosterone (DHEA) therapy, and stem cell therapy. Stem cell therapy has proven to be the most efficient form for treating POF as compared to all other options. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are the best among the other sources of mesenchymal stem cells (MSCs) for the treatment of POF as they have a painless extraction procedure. They have a tremendous capacity for self-repair and regeneration, which helps them in restoring degenerated ovaries. This review includes informationon the causes of POF, its efficacious therapeutic approaches, and the impact of transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs) as an option for the therapy of POF. Numerous studies conducted on stem cell therapy provethat it is an effective approach for the treatment of sterility.

Evaluating the effect of LPS from periodontal pathogenic bacteria on the expression of senescence-related genes in human dental pulp stem cells.

The human dental pulp stem cells (hDPSCs) are one of the readily available sources of multipotent mesenchymal stem cells (MSCs) and can be considered as a type of tool cells for cell-based therapies. However, the main limitation in the clinical use of these cells is DPSC senescence, which can be induced by lipopolysaccharide (LPS) of oral pathogenic bacteria. Up to now, far little attention has been paid to exploring the molecular mechanisms of senescence in DPSCs. So, the current study aimed to investigate the underlying molecular mechanism of senescence in hDPSCs stimulated with Porphyromonas gingivalis (P. gingivalis) and Escherichia coli (E. coli)-derived LPSs, by evaluating both mRNA and protein expression of four important senescence-related genes, including TP53, CDKN1A, CDKN2A and SIRT1. To this purpose, hDPSCs were stimulated with different LPSs for 6, 24 and 48 h and then the gene expression was evaluated using quantitative real-time polymerase chain reaction (qPCR) and western blotting. Following stimulation with P. gingivalis and E. coli-derived LPSs, the relative mRNA and protein expression of all genes were significantly up-regulated in a time-dependent manner, as compared with unstimulated hDPSCs. Moreover, the hDPSCs stimulated with P. gingivalis LPS for 6 and 24 h had the highest mRNA expression of CDKN1A and SIRT1, respectively (p &lt; 0.0001), whereas the highest mRNA expression of CDKN2A and TP53 was seen in hDPSCs stimulated with E. coli LPS for 48 h (p &lt; 0.0001). In summary, because DPSCs have been reported to have therapeutic potential for several cell-based therapies, targeting molecular mechanisms aiming at preventing DPSC senescence could be considered a valuable strategy.

Validation of a color deconvolution method to quantify MSC tri-lineage differentiation across species.

Mesenchymal stem cells (MSCs) are a promising candidate for both human and veterinary regenerative medicine applications because of their abundance and ability to differentiate into several lineages. Mesenchymal stem cells are however a heterogeneous cell population and as such, it is imperative that they are unequivocally characterized to acquire reproducible results in clinical trials. Although the tri-lineage differentiation potential of MSCs is reported in most veterinary studies, a qualitative evaluation of representative histological images does not always unambiguously confirm tri-lineage differentiation. Moreover, potential differences in differentiation capacity are not identified. Therefore, quantification of tri-lineage differentiation would greatly enhance proper characterization of MSCs. In this study, a method to quantify the tri-lineage differentiation potential of MSCs is described using digital image analysis, based on the color deconvolution plug-in (ImageJ). Mesenchymal stem cells from three species, i.e., bovine, equine, and porcine, were differentiated toward adipocytes, chondrocytes, and osteocytes. Subsequently, differentiated MSCs were stained with Oil Red O, Alcian Blue, and Alizarin Red S, respectively. Next, a differentiation ratio (DR) was obtained by dividing the area % of the differentiation signal by the area % of the nuclear signal. Although MSCs isolated from all donors in all species were capable of tri-lineage differentiation, differences were demonstrated between donors using this quantitative DR. Our straightforward, simple but robust method represents an elegant approach to determine the degree of MSC tri-lineage differentiation across species. As such, differences in differentiation potential within the heterogeneous MSC population and between different MSC sources can easily be identified, which will support further optimization of regenerative therapies.

Dental pulp stem cells retain mesenchymal phenotype despite differentiation toward retinal neuronal fate in vitro

Dental pulp stem cells (DPSCs) are an easily accessible, heterogenous source of mesenchymal stem cells (MSCs) that are derived from the neural crest. Evidence suggests that they have neurotrophic qualities in their undifferentiated state and can also be differentiated into neuronal and retinal cell types. There is growing interest in using DPSCs in cell-based therapies to treat glaucoma and blinding retinal diseases. However, careful characterization of these cells is necessary as direct intravitreal and subretinal MSC transplantation is known to lead to deleterious glial reaction and fibrosis. In this study, we provide evidence for the mesenchymal-predominant nature of DPSCs and show that DPSCs maintain their mesenchymal phenotype despite upregulating mature retinal markers under retinal differentiation conditions. CD56, which was previously thought to be a specific marker of neural crest lineage, is robustly co-expressed with mesenchymal markers and may not be adequate for isolating a subpopulation of neural crest cells in DPSCs. Therefore, identification of more specific markers is required to elucidate the heterogeneity of the population and to successfully isolate a putative neural stem cell population before DPSCs can be used for retinal therapy.

Adipose-derived mesenchymal stem cells and wound healing: Potential clinical applications in wound repair.

Delayed and chronic wounds result from the dysregulation of molecular and cellular events associated with wound healing, including migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. Adipose tissue is an abundant, easily accessible, and rich source of mesenchymal stem cells (MSCs) with high therapeutic potential. In addition to their capability to differentiate into various lineages with specialized functions, adipose-derived MSCs (AMSCs) can mediate to the wound repair process through the secretion of different growth factors and mediators rather than making structural contribution alone. Adipose-derived MSCs mediate the formation of blood vessels, recruit progenitor cells, stimulate cell differentiation and ECM formation, and promote wound healing by releasing immune mediators and exosomes. Herein, we discuss and review the therapeutic potential of AMSCs for wound repair via acceleration of wound closure, re-epithelialization, enhancement of angiogenesis and immunomodulation of prolonged inflammatory responses, as well as the current challenges in clinical implementation.

Research trends of mesenchymal stem cells application in orthopedics: A bibliometric analysis of the past 2 decades.

BackgroundBibliometric analysis and visualization tools were used to determine the development trend of mesenchymal stem cells (MSCs) in orthopedics in the past 20 years, so as to guide researchers to explore new directions and hotspots in the field in the future.MethodsIn the Web of Science Core Collection, all articles about the application of MSCs in orthopedics from 2002 to 2021 were searched. The qualitative and quantitative analysis was performed based on Web of Science and CiteSpace software.ResultsA total of 2,207 articles were retrieved. After excluding non-article articles such as review and letter and non-English language articles, 1,489 articles were finally included. Over the past 2 decades, the number of publications on the application of MSCs in orthopedic diseases increased. Among them, the United States, China, Japan and the United Kingdom have made significant contributions in this field. The most productive institution was Shanghai Jiao Tong University. Journal of Orthopedic Research published the largest number of publications. The journal with the highest citation frequency was Experimental Hematology. The authors with the highest output and the highest citation frequency on average were Rochy S. Tuan and Scott A. Rodeo, respectively. “Mesenchymal stem cell”, “in vitro” and “Differentiation” were the top three keywords that appeared. From the keyword analysis, the current research trend indicates that the primary research hotspots of MSCs in orthopedics are the source of MSCs, in vitro experiments and the differentiation of MSCs into bone and cartilage. The frontiers of this field are the combination of MSCs and platelet-rich plasma (PRP), the treatment of knee diseases such as osteoarthritis, osteogenic differentiation, and the application of biological scaffolds combined with MSCs.ConclusionOver the past 2 decades, the application of MSCs in orthopedic diseases has received increasing attention. Our bibliometric analysis results provide valuable information and research trends for researchers in the field to understand the basic knowledge of the field, identify current research hotspots, potential collaborators, and future research frontiers.

Cellular Aging Secretes: a Comparison of Bone-Marrow-Derived and Induced Mesenchymal Stem Cells and Their Secretome Over Long-Term Culture.

Mesenchymal stem cells (MSCs) hold promising therapeutic potential in several clinical applications, mainly due to their paracrine activity. The implementation of future secretome-based therapeutic strategies requires the use of easily accessible MSCs sources that provide high numbers of cells with homogenous characteristics. MSCs obtained from induced pluripotent stem cells (iMSCs) have been put forward as an advantageous alternative to the gold-standard tissue sources, such as bone marrow (BM-MSCs). In this study, we aimed at comparing the secretome of BM-MSCs and iMSCs over long-term culture. For that, we performed a broad characterization of both sources regarding their identity, proteomic secretome analysis, as well as replicative senescence and associated phenotypes, including its effects on MSCs secretome composition and immunomodulatory action. Our results evidence a rejuvenated phenotype of iMSCs, which is translated into a superior proliferative capacity before the induction of replicative senescence. Despite this significant difference between iMSCs and BM-MSCs proliferation, both untargeted and targeted proteomic analysis revealed a similar secretome composition for both sources in pre-senescent and senescent states. These results suggest that shifting from the use of BM-MSCs to a more advantageous source, like iMSCs, may yield similar therapeutic effects as identified over the past years for this gold-standard MSC source.

Injectable Peptide Hydrogel Encapsulation of Mesenchymal Stem Cells Improved Viability, Stemness, Anti-Inflammatory Effects, and Early Stage Wound Healing.

Human-adipose-derived mesenchymal stem cells (hADMSCs) are adult stem cells and are relatively easy to access compared to other sources of mesenchymal stem cells (MSCs). They have shown immunomodulation properties as well as effects in improving tissue regeneration. To better stimulate and preserve the therapeutic properties of hADMSCs, biomaterials for cell delivery have been studied extensively. To date, hyaluronic acid (HA)-based materials have been most widely adopted by researchers around the world. PGmatrix is a new peptide-based hydrogel that has shown superior functional properties in 3D cell cultures. Here, we reported the in vitro and in vivo functional effects of PGmatrix on hADMSCs in comparison with HA and HA-based Hystem hydrogels. Our results showed that PGmatrix was far superior in maintaining hADMSC viability during prolonged incubation and stimulated expression of SSEA4 (stage-specific embryonic antigen-4) in hADMSCs. hADMSCs encapsulated in PGmatrix secreted more immune-responsive proteins than those in HA or Hystem, though similar VEGF-A and TGFβ1 release levels were observed in all three hydrogels. In vivo studies revealed that hADMSCs encapsulated with PGmatrix showed improved skin wound healing in diabetic-induced mice at an early stage, suggesting possible anti-inflammatory effects, though similar re-epithelialization and collagen density were observed among PGmatrix and HA or Hystem hydrogels by day 21.

Comprehensive Analysis of Novel Genes and Pathways Associated with Osteogenic Differentiation of Adipose Stem Cells.

Background Adipose-derived stem cells (ADSCs) are an important alternative source of mesenchymal stem cells (MSCs) and show great promise in tissue engineering and regenerative medicine applications. However, identifying the novel genes and pathways and finding the underlying mechanisms regulating ADSCs osteogenic differentiation remain urgent. Methods We downloaded the gene expression profiles of GSE63754 and GSE37329 from the Gene Expression Omnibus (GEO) Database. We derived differentially expressed genes (DEGs) before and after ADSC osteogenic differentiation, followed by Gene Ontology (GO) functional and KEGG pathway analysis and protein-protein interaction (PPI) network analysis. 211 differentially expressed genes (142 upregulated genes and 69 downregulated genes) were aberrantly expressed. GO analysis revealed that these DEGs were associated with extracellular matrix organization, protein extracellular matrix, and semaphorin receptor binding. Conclusions Our study provides novel genes and pathways that play important roles in regulating ADSC osteogenic differentiation, which may have potential therapeutic targets for clinic.

Down-Regulation of CXCR4 in Mesenchymal Stem Cells by Septic Serum.

Sepsis is one of the main concerns of health and one of the leading causes of death in hospitals. It is essential to manage sepsis in hospitalized patients. In recent years, cell therapy has been considered as a new approach to treat sepsis. This study evaluated the effect of CXCR4 as one of the main proteins involved in the homing of mesenchymal stem cells in the sepsis serum in mice model. Mouse sepsis model was induced by injection of E.coli and biochemical analyses was done to confirm the organ failure. Mesenchymal stem cells (MSCs) derived from bone marrow were separated into sepsis and control groups. In the sepsis serum group, MSCs were treated with sepsis serum at two time points: 24 and 48h. Quantitative RT-PCR and flow cytometry were performed to determine the mRNA expression of CXCR4 in sepsis serum group compared to control group. Also, a migration assay was done to assess the migration capacity of bone marrow MSCs during inflammation and treatment in sepsis. Our result showed that treatment with sepsis serum can control migration by decrease in CXCR4 level (P ≤ 0.05) compared to control group. Moreover it was also reported that sepsis serum decreased mRNA expression of CXCR4 in MScs. In our study, MSCs treated with septic serum were no longer able to migrate . Probably many variables such as source, dose, injection time, and injection route of MSCs after sepsis induction in the animal models are key factors for successful cell therapy.

The Neural Multilineage Differentiation Capacity of Human Neural Precursors from the Umbilical Cord-Ready to Bench for Clinical Trials.

Mesenchymal stem cells (MSC) are promising for regenerative medicine as they have a vast differentiation capacity, immunomodulatory properties and can be isolated from different tissues. Among them, the umbilical cord is considered a good source of MSC, as its collection poses no risk to donors and is unrelated to ethical issues. Furthermore, umbilical cord mesenchymal stem cells (UC-MSC) can differentiate into several cell lines, including neural lineages that, in the future, may become an alternative in the treatment of neurodegenerative diseases. This study used a natural functional biopolymer matrix (NFBX) as a membrane to differentiate UC-MSC into neurospheres and their Neural precursors without using neurogenic growth factors or gene transfection. Through the characterization of Neural precursors and differentiated cells, it was possible to demonstrate the broad potential for the differentiation of cells obtained through cultivation on this membrane. To demonstrate these Neural precursors’ potential for future studies in neurodegenerative diseases, the Neural precursors from Wharton’s jelly were differentiated into Schwann cells, oligodendrocytes, cholinergic-, dopaminergic- and GABAergic-like neurons.

Preventive effects of bone marrow-derived mesenchymal stem cell transplantation in a D-galactose-induced brain aging in rats.

Aging is a complex process accompanied by numerous morphological, functional, and metabolic impairments in the brain, and a critical risk factor involved in the increasing incidence of neurodegenerative diseases. Few studies have evaluated the efficacy of different sources of mesenchymal stem cells (MSCs) in ameliorating the early morphological and functional alterations in the aging brain. This study, for the first time, evaluated the potential efficacy of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose-induced rat model of brain aging. BMMSCs (1 × 10⁶) were intravenously injected into brain aging model rats once every 2 weeks for 8 weeks. The transplanted cells survived and migrated to the brain, and differentiated into astrocytes and neurons, including choline acetyltransferase neurons. BMMSC transplantation improved locomotor activity and cognitive functions, restored cholinergic system function, protected atrophic cholinergic neurons in the basal forebrain, induced antioxidative effects and restored neurotrophic factors, and modulated hippocampal synaptic plasticity by upregulating PSD95 and Egr1 expression. Our findings demonstrated the efficacy of BMMSC injection in an aging rat model and suggest that these cells may be developed into an effective cell therapy for the aging brain.

Mesenchymal stem cell therapy: A review of clinical trials for multiple sclerosis.

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is the result of the body's own immune cells being auto-reactive to the myelin regions of the body as if these regions were foreign antigens. This demyelination process is damaging to the electrical conductivity of neurons. The current medicines are only capable of fighting off the symptoms of the disease, but not the disease itself. Specialized stem cells, known as mesenchymal stem cells (MSCs), seem to be the candidate therapy to get rid of MS. MSCs can be isolated from multiple sources of the person's body, and even from the umbilical cord (UC) and placenta of a donor. These cells have anti-inflammatory effects so they can target the overactivity and self-antigen attacks by T cells and macrophages; this immune system overactivity is characteristic of MS. MSCs show the ability to locate into brain lesions when injected and thus can compensate for the loss of the brain function by differentiating into neuronal precursor cells and glial cells. The author has listed tables of clinical trials that have utilized MSCs from different sources, along with the years and the phase of study completed for each trial. The consensus is that these cells work on inhibiting CD4+ and CD8+ T cell activation, T regulatory cells (Tregs), and macrophage switch into the auto-immune phenotype.The best source of MSCs seems to be the UC due to the easiness of extraction, the noninvasive method of collection, their higher expansion ability and more powerful immune-modulating properties compared to other locations in the body. Studies showed there was a significant decline of mRNA expression of several cytokines after the administration of MSCs derived from the UC (UCMSCs). Other researchers were able to repair the defects of Tregs in MS patients by co-culturing Tregs from these patients with UCMSCs, which decreased the production of the pro-inflammatory cytokine IFN , and also suggested a strong link between Tregs lack of functionality in MS patients with the pathogenesis of the disease.

Mesenchymal (Stem) Stromal Cells Based as New Therapeutic Alternative in Inflammatory Bowel Disease: Basic Mechanisms, Experimental and Clinical Evidence, and Challenges.

Inflammatory bowel diseases (IBD) are an example of chronic diseases affecting 40% of the population, which involved tissue damage and an inflammatory process not satisfactorily controlled with current therapies. Data suggest that mesenchymal stem cells (MSC) may be a therapeutic option for these processes, and especially for IBD, due to their multifactorial approaches such as anti-inflammatory, anti-oxidative stress, anti-apoptotic, anti-fibrotic, regenerative, angiogenic, anti-tumor, or anti-microbial. However, MSC therapy is associated with important limitations as safety issues, handling difficulties for therapeutic purposes, and high economic cost. MSC-derived secretome products (conditioned medium or extracellular vesicles) are therefore a therapeutic option in IBD as they exhibit similar effects to their parent cells and avoid the issues of cell therapy. In this review, we proposed further studies to choose the ideal tissue source of MSC to treat IBD, the implementation of new standardized production strategies, quality controls and the integration of other technologies, such as hydrogels, which may improve the therapeutic effects of derived-MSC secretome products in IBD.