Project description:Oral mesenchymal stem/progenitor cells (MSCs) are renowned in the field of tissue engineering/regeneration for their multilineage differentiation potential and easy acquisition. These cells encompass the periodontal ligament stem/progenitor cells (PDLSCs), the dental pulp stem/progenitor cells (DPSCs), the stem/progenitor cells from human exfoliated deciduous teeth (SHED), the gingival mesenchymal stem/progenitor cells (GMSCs), the stem/progenitor cells from the apical papilla (SCAP), the dental follicle stem/progenitor cells (DFSCs), the bone marrow mesenchymal stem/progenitor cells (BM-MSCs) from the alveolar bone proper, and the human periapical cyst-mesenchymal stem cells (hPCy-MSCs). Apart from their remarkable regenerative potential, oral MSCs possess the capacity to interact with an inflammatory microenvironment. Although inflammation might affect the properties of oral MSCs, they could inversely exert a multitude of immunological actions to the local inflammatory microenvironment. The present review discusses the current understanding about the immunomodulatory role of oral MSCs both in periodontitis and systemic diseases, their "double-edged sword" uniqueness in inflammatory regulation, their affection of the immune system, and the underlying mechanisms, involving oral MSC-derived extracellular vesicles.
Project description:Mesenchymal stem cells (MSCs) have broad-based therapeutic potential in regenerative medicine. However, a major barrier to their clinical utility is that MSCs from different tissues are highly variable in their regenerative properties. In this study, we defined the molecular and phenotypic identities of different MSC populations from different osseous tissue sites of different patients and, additionally, determined their respective regenerative properties. MSCs from 6 patients were isolated from either bone marrow of the iliac crest (BMSCs) or alveolar bone tissue (aBMSCs), and flow cytometry revealed that regardless of the tissue source, MSC immunotypes had the same expression of MSC markers CD73, CD90, and CD105. However, transcriptomic analyses revealed 589 genes differentially expressed (DE) between BMSCs and aBMSCs, including eightfold higher levels of bone morphogenetic protein 4 (BMP-4) in aBMSCs. In striking contrast, gene expression of MSCs derived from the same tissue, but between different patients (i.e., BMSCs to BMSCs, aBMSCs to aBMSCs), showed only 38 DE BMSC genes and 51 DE aBMSC genes. A protein array showed that aBMSC and BMSC produced equivalent levels of angiogenic cytokines; however, when placed in angiogenesis model systems, aBMSCs induced significantly more capillaries in vitro and in vivo. Finally, cell transplantation of MSCS into osseous defects showed that the bone regenerative capacity of aBMSCs was significantly greater than that of BMSCs. This study is the first to link the molecular, phenotypic, and regenerative properties of different MSCs from different patients and provides novel insights toward MSC differences based on the osseous tissue origin.
Project description:Mesenchymal stem/stromal cells (MSCs) are widely distributed in the body and play essential roles in tissue regeneration and homeostasis. MSCs can be isolated from discarded tissues, expanded in vitro and used as therapeutics for autoimmune diseases and other chronic disorders. MSCs promote tissue regeneration and homeostasis by primarily acting on immune cells. At least six different types of MSCs have been isolated from postnatal dental tissues and have remarkable immunomodulatory properties. Dental stem cells (DSCs) have been demonstrated to have therapeutic effects on several systemic inflammatory diseases. Conversely, MSCs derived from nondental tissues such as the umbilical cord exhibit great benefits in the management of periodontitis in preclinical studies. Here, we discuss the main therapeutic uses of MSCs/DSCs, their mechanisms, extrinsic inflammatory cues and the intrinsic metabolic circuitries that govern the immunomodulatory functions of MSCs/DSCs. Increased understanding of the mechanisms underpinning the immunomodulatory functions of MSCs/DSCs is expected to aid in the development of more potent and precise MSC/DSC-based therapeutics.
Project description:Mesenchymal stem cells (MSCs) are regarded as highly promising cells for allogeneic cell therapy, owing to their multipotent nature and ability to display potent and varied functions in different diseases. The functions of MSCs, including native immunomodulation, high self-renewal characteristic, and secretory and trophic properties, can be employed to improve the immune-modulatory functions in diseases. MSCs impact most immune cells by directly contacting and/or secreting positive microenvironmental factors to influence them. Previous studies have reported that the immunomodulatory role of MSCs is basically dependent on their secretion ability from MSCs. This review discusses the immunomodulatory capabilities of MSCs and the promising strategies to successfully improve the potential utilization of MSCs in clinical research.
Project description:Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in several dental tissues (D-MSCs). Clinical trials in which cells from these sources were used have shown that they are effective and safe as treatments for tissue regeneration. Importantly, immunoregulatory capacity has been observed in all of these populations; however, this function may vary among the different types of MSCs. Since this property is of clinical interest for cell therapy protocols, it is relevant to analyze the differences in immunoregulatory capacity, as well as the mechanisms used by each type of MSC. Interestingly, D-MSCs are the most suitable source for regenerating mineralized tissues in the oral region. Furthermore, the clinical potential of D-MSCs is supported due to their adequate capacity for proliferation, migration, and differentiation. There is also evidence for their potential application in protocols against autoimmune diseases and other inflammatory conditions due to their immunosuppressive capacity. Therefore, in this review, the immunoregulatory mechanisms identified at the preclinical level in combination with the different types of MSCs found in dental tissues are described, in addition to a description of the clinical trials in which MSCs from these sources have been applied.
Project description:Adipose derived Mesenchymal stem cells (AMSCs) are able to expand in vitro and undergo differentiation into multiple cell lineages, yet have low immunogenicity while exhibiting several immunoregulatory characteristics. We sought to investigate the immunomodulatory mechanisms of AMSCs to better understand their immunogenic properties. Following 10 days of chondrogenic differentiation or 48 hours of IFN-γ pretreatment, AMSCs retained low level immunogenicity but prominent immunoregulatory activity and AMSC immunogenicity was enhanced by chondrogenic differentiation or IFN-γ treatment. We found Jagged-2 expression was significantly elevated following chondrogenic differentiation or IFN-γ pretreatment. Jagged-2-RNA interference experiments suggested that Jagged-2-siRNA2 suppresses Jagged-2 expression during chondrogenic differentiation and in IFN-γ pretreated AMSCs. Besides, Jagged-2 interference attenuated immunosuppressive activity by mixed lymphocyte culture and mitogen stimulation experiments. So, the immunoregulatory activity of AMSCs, to some extent dependent upon Jagged-2, might be stronger after multilineage differentiation or influence from inflammatory factors. This may also be why rejection does not occur after allogeneic AMSCs differentiate into committed cells.
Project description:The world has witnessed unimaginable damage from the coronavirus disease-19 (COVID-19) pandemic. Because the pandemic is growing rapidly, it is important to consider diverse treatment options to effectively treat people worldwide. Since the immune system is at the hub of the infection, it is essential to regulate the dynamic balance in order to prevent the overexaggerated immune responses that subsequently result in multiorgan damage. The use of stem cells as treatment options has gained tremendous momentum in the past decade. The revolutionary measures in science have brought to the world mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exo) as therapeutic opportunities for various diseases. The MSCs and MSCExos have immunomodulatory functions; they can be used as therapy to strike a balance in the immune cells of patients with COVID-19. In this review, we discuss the basics of the cytokine storm in COVID-19, MSCs, and MSC-derived exosomes and the potential and stem-cell-based ongoing clinical trials for COVID-19. [BMB Reports 2020; 53(8): 400-412].
Project description:IntroductionStem cell therapy with mesenchymal stem cells (MSCs) has been widely used in many clinical trials, and therapy with MSC sheets shows promise for patients. However, there are few reports characterizing MSC sheets. In the present study, the properties of MSC sheets derived from bone marrow, adipose tissue, and umbilical cord were evaluated.MethodsCell sheets were fabricated with MSCs from different tissue origins in temperature-responsive cell culture dishes with and without pre-coating of fetal bovine serum (FBS). MSC adhesion behavior in the culture dish was observed. Secretion of cytokines related to cell proliferation and immune regulation from MSC sheets was investigated by ELISA. The adhesion properties of the MSC sheets were investigated by time-lapse microscopy.ResultsDifferent cell adhesion and proliferation rates in temperature-responsive cell culture dishes were observed among the three types of MSCs. FBS pre-coating of the dishes enhanced cell attachment and proliferation in all cell types. Harvested cell sheets showed high attachment capacity to tissue culture polystyrene dish surfaces.ConclusionsMSC sheets can be fabricated from MSCs from different tissue origins using temperature-responsive cell culture dishes. The fabricated MSC sheets could be useful in cell transplantation therapies by choosing appropriate types of MSCs that secrete therapeutic cytokines for the targeted diseases.
Project description:ObjectiveResearch has shown promise of using bone marrow mesenchymal stem cells (BMSCs) for craniofacial bone regeneration; yet little is known about the differences of BMSCs from limb and craniofacial bones. This study compared pig mandibular and tibia BMSCs for their in vitro proliferation, osteogenic differentiation properties and gene expression.DesignBone marrow was aspirated from the tibia and mandible of 3-4 month-old pigs (n=4), followed by BMSC isolation, culture-expansion and characterization by flow cytometry. Proliferation rates were assessed using population doubling times. Osteogenic differentiation was evaluated by alkaline phosphatase activity. Affymetrix porcine microarray was used to compare gene expressions of tibial and mandibular BMSCs, followed by real-time RT-PCR evaluation of certain genes.ResultsOur results showed that BMSCs from both locations expressed MSC markers but not hematopoietic markers. The proliferation and osteogenic differentiation potential of mandibular BMSCs were significantly stronger than those of tibial BMSCs. Microarray analysis identified 404 highly abundant genes, out of which 334 genes were matched between the two locations and annotated into the same functional groups including osteogenesis and angiogenesis, while 70 genes were mismatched and annotated into different functional groups. In addition, 48 genes were differentially expressed by at least 1.5-fold difference between the two locations, including higher expression of cranial neural crest-related gene BMP-4 in mandibular BMSCs, which was confirmed by real-time RT-PCR.ConclusionsAltogether, these data indicate that despite strong similarities in gene expression between mandibular and tibial BMSCs, mandibular BMSCs express some genes differently than tibial BMSCs and have a phenotypic profile that may make them advantageous for craniofacial bone regeneration.
Project description:Mesenchymal stem cells (MSCs) have been used experimentally and clinically in the treatment of a wide variety of pathologies. It is now clear that a number of different mechanisms contribute to the therapeutic effects exerted by these cells. The ability of MSCs to interact with and modulate the functions of a wide variety of immune cells has been recognized as one such mechanism. The implications that the immunomodulatory properties of MSCs may have for the treatment of solid organ rejection, the Systemic Inflammatory Response Syndrome, cancer, and Crohn's disease are reviewed herein.