Multipotent Mesenchymal Cells Research Articles

Immunophenotyping of a population of cultured human umbilical cord cells from Wharton's jelly

BACKGROUND: Against the background of many existing methods of defect replacement in post-traumatic injuries the methods of repair of damaged tissues based on methods using products of tissue engineering and cultures of artificially cultured human cells are becoming more and more widespread in medical practice. The literature reports weak immunogenic activity of human umbilical cord tissues, which makes these cells promising components of regenerative medicine products. Due to possible errors in explant selection and cell transformation in the process of cultivation, it is necessary to reliably determine the phenotype of cells obtained as a result of tissue explantation and their further cultivation. Thus, the specificity of obtaining multipotent mesenchymal cells from human umbilical cord Warton's stool tissues requires reliable identification of the type of the obtained cells. AIM: To obtain reliable features of mesenchymal stem cells in the cell population obtained from human umbilical cord stool tissue. MATERIAL AND METHODS: Methods of cell cultivation, flow cytofluorimetry, immunocytochemistry for determination of surface and intracellular markers of mesenchymal stem cells were used in the study. RESULTS: In the course of work on the identification of cells of the population obtained by culturing explants from human umbilical cord Wharton stool, the heterogeneity of the type of cells constituting the cell population was established. Most of them are mesenchymal stem cells carrying fluorescent markers CD45, CD73, CD34, CD29, CD90, CD44, CD105, which agrees with the immunophenotype of mesenchymal stem cells defined by the International Society for Cell Therapy. The ratio of the applied markers allows us to refer the population of cells obtained by direct explantation of Varton's gelatin tissue fragments to mesenchymal stem cells. Visual control confirmed the localisation of labelled antibodies on the surface of cultured cells. And also, it was shown that there were no vascular muscle cells in the obtained culture. CONCLUSION: As a result of experiments on identification of the cells obtained during explantation of Wharton's jelly tissue fragments and their further cultivation, their belonging to mesenchymal stem cells was established by immunofluorescence cytophotometry.

Stem cell therapy for cardiac regeneration: key points

Cardiovascular diseases are a leading cause of disability and mortality among the working population, necessitating the development and implementation of new, more effective treatment and rehabilitation methods for such patients, including the use of modern cellular and tissue technologies. In this review, an analysis and summary of research results over the past decades regarding the effectiveness of various types of stem cells in heart pathology were conducted. Priority directions include the search for more accessible and safe sources of stem cells, the development of new effective methods for their cultivation, and the use of scaffolds for transplantation. Given the pathogenetic mechanisms of cardiovascular pathology and myocardial regeneration, particular interest for clinical application is drawn to tissue-specific progenitors from the myocardium for replacing injured cardiomyocytes, endothelial progenitors for correcting accompanying endothelial dysfunction, and multipotent mesenchymal cells of various origins with low immunogenicity that exhibit trophic, anti-inflammatory, immunomodulatory, and anti-apoptotic effects. Questions regarding the optimal method, dose, and frequency of stem cell administration, as well as the standardization of criteria for their quality and effectiveness, remain open. Additionally, the combined use of different types of stem cells may serve as a new priority strategy in assessing the effectiveness and safety of cell therapy, especially considering the paradigm of repeated transplantation. The successful translation of obtained preclinical results into further large, well-planned, placebo-controlled clinical trials will enhance the safety and effectiveness of cell therapy for cardiovascular diseases, which is one of the current challenges of modern regenerative medicine.

Multipotent Mesenchymal Cells Homing and Differentiation on Poly(ε-caprolactone) Blended with 20% Tricalcium Phosphate and Polylactic Acid Incorporating 10% Hydroxyapatite 3D-Printed Scaffolds via a Commercial Fused Deposition Modeling 3D Device.

As highlighted by the 'Global Burden of Disease Study 2019' conducted by the World Health Organization, ensuring fair access to medical care through affordable and targeted treatments remains crucial for an ethical global healthcare system. Given the escalating demand for advanced and urgently needed solutions in regenerative bone procedures, the critical role of biopolymers emerges as a paramount necessity, offering a groundbreaking avenue to address pressing medical needs and revolutionize the landscape of bone regeneration therapies. Polymers emerge as excellent solutions due to their versatility, making them reliable materials for 3D printing. The development and widespread adoption of this technology would impact production costs and enhance access to related healthcare services. For instance, in dentistry, the use of commercial polymers blended with β-tricalcium phosphate (TCP) is driven by the need to print a standardized product with osteoconductive features. However, modernization is required to bridge the gap between biomaterial innovation and the ability to print them through commercial printing devices. Here we showed, for the first time, the metabolic behavior and the lineage commitment of bone marrow-derived multipotent mesenchymal cells (MSCs) on the 3D-printed substrates poly(e-caprolactone) combined with 20% tricalcium phosphate (PCL + 20% β-TCP) and L-polylactic acid (PLLA) combined with 10% hydroxyapatite (PLLA + 10% HA). Although there are limitations in printing additive-enriched polymers with a predictable and short half-life, the tested 3D-printed biomaterials were highly efficient in supporting osteoinductivity. Indeed, considering different temporal sequences, both 3D-printed biomaterials resulted as optimal scaffolds for MSCs' commitment toward mature bone cells. Of interest, PLLA + 10% HA substrates hold the confirmation as the finest material for osteoinduction of MSCs.

Bioactive and electrically conductive GelMA-BG-MWCNT nanocomposite hydrogel bone biomaterials

Natural bone is a complex organic-inorganic composite tissue that possesses endogenous electrically conductive properties in response to mechanical forces. Mimicking these unique properties collectively in a single synthetic biomaterial has so far remained a formidable task. In this study, we report a synthesis strategy that comprised gelatin methacryloyl (GelMA), sol-gel derived tertiary bioactive glass (BG), and uniformly dispersed multiwall carbon nanotubes (MWCNTs) to create nanocomposite hydrogels that mimic the organic-inorganic composition of bone. Using this strategy, biomaterials that are electrically conductive and possess electro-mechanical properties similar to endogenous bone were prepared without affecting their biocompatibility. Nanocomposite hydrogel biomaterials were biodegradable and promoted biomineralization, and supported multipotent mesenchymal progenitor cell (10T1/2) cell interactions and differentiation into an osteogenic lineage. To the best of our knowledge, this work presents the first study to functionally characterize suitable electro-mechanical responses in nanocomposite hydrogels, a key process that occurs in the natural bone to drive its repair and regeneration. Overall, the results demonstrated GelMA-BG-MWCNT nanocomposite hydrogels have the potential to become promising bioactive biomaterials for use in bone repair and regeneration.

TIAM1 acts as an actin organization regulator to control adipose tissue-derived pericyte cell fate.

Pericytes are multipotent mesenchymal precursor cells that demonstrate tissue-specific properties. In this study, by comparing human adipose tissue- and periosteum-derived pericyte microarrays, we identified T cell lymphoma invasion and metastasis 1 (TIAM1) as a key regulator of cell morphology and differentiation decisions. TIAM1 represented a tissue-specific determinant between predispositions for adipocytic versus osteoblastic differentiation in human adipose tissue-derived pericytes. TIAM1 overexpression promoted an adipogenic phenotype, whereas its downregulation amplified osteogenic differentiation. These results were replicated in vivo, in which TIAM1 misexpression altered bone or adipose tissue generation in an intramuscular xenograft animal model. Changes in pericyte differentiation potential induced by TIAM1 misexpression correlated with actin organization and altered cytoskeletal morphology. Small molecule inhibitors of either small GTPase Rac1 or RhoA/ROCK signaling reversed TIAM1-induced morphology and differentiation in pericytes. In summary, our results demonstrate that TIAM1 regulates the cellular morphology and differentiation potential of human pericytes, representing a molecular switch between osteogenic and adipogenic cell fates.

Tight Regulation of Mechanotransducer Proteins Distinguishes the Response of Adult Multipotent Mesenchymal Cells on PBCE-Derivative Polymer Films with Different Hydrophilicity and Stiffness.

Mechanotransduction is a molecular process by which cells translate physical stimuli exerted by the external environment into biochemical pathways to orchestrate the cellular shape and function. Even with the advancements in the field, the molecular events leading to the signal cascade are still unclear. The current biotechnology of tissue engineering offers the opportunity to study in vitro the effect of the physical stimuli exerted by biomaterial on stem cells and the mechanotransduction pathway involved in the process. Here, we cultured multipotent human mesenchymal/stromal cells (hMSCs) isolated from bone marrow (hBM-MSCs) and adipose tissue (hASCs) on films of poly(butylene 1,4-cyclohexane dicarboxylate) (PBCE) and a PBCE-based copolymer containing 50 mol% of butylene diglycolate co-units (BDG50), to intentionally tune the surface hydrophilicity and the stiffness (PBCE = 560 Mpa; BDG50 = 94 MPa). We demonstrated the activated distinctive mechanotransduction pathways, resulting in the acquisition of an elongated shape in hBM-MSCs on the BDG50 film and in maintaining the canonical morphology on the PBCE film. Notably, hASCs acquired a new, elongated morphology on both the PBCE and BDG50 films. We found that these events were mainly due to the differences in the expression of Cofilin1, Vimentin, Filamin A, and Talin, which established highly sensitive machinery by which, rather than hASCs, hBM-MSCs distinguished PBCE from BDG50 films.

Histopathological study of ovarian lesions at a tertiary health-care center

Background: Ovary is the most common site of non-neoplastic and neoplastic lesions, can appear at any age, and is the leading cause of hospitalization and surgery. The ovary is made up of totipotent sex cells and multipotent mesenchymal cells. As a result, when it becomes neoplastic, almost any type of tumor can develop. Aims and Objectives: The aim of the study was to find out the histopathological findings of ovarian lesions. Materials and Methods: The present study was carried out in the Department of Pathology, Pacific Institute of Medical Sciences, Udaipur, from April 2021 to September 2022 and includes 102 cases of ovarian lesions. Histopathology department received the specimens in formalin filled container and performed routine grossing and H and E staining procedure. Results: The incidence of neoplastic ovarian lesion was 40.2%. Majority of non-neoplastic lesion of ovary was follicular cyst (42.6%) followed by simple cyst (36.1%). Surface epithelial tumor was diagnosed in majority of ovarian tumors (73.2%) followed by germ cell tumor (22.0%). The majority histopathological benign tumor type was serous cystadenoma (43.9%) and malignant was high-grade serous carcinoma (14.63%). Conclusion: The incidence rate increased with age, with the greatest number of new cases being diagnosed beyond 4th and 5th decade. In our study, the youngest patient was of 2 year and oldest was of more than 60 years. However, histopathological study of ovarian tumors is still considered as a gold standard method, our observations and results proved to be valuable base line information regarding frequency and pattern of ovarian tumors.

Relative survival and cell adhesion of multipotent mesenchymal cells from primary teeth pulp on the surface membranes and sponges produced from collagen

To study the behavior of SHED cell culture on different types of materials for the regeneration of periodontal tissues with different porosity. Porous collagen material Fibro-Gide (Geitstlich Pharma AG, Switzerland), designed to increase the volume of the gum and the barrier collagen membrane Bio-Gide (Geitstlich Pharma AG, Switzerland) were studied in vitro on SHED cultures. As a control sample, a Spongostan sponge made of gelatin (Johnson & Johnson Medical, UK) with the most pronounced porosity and wettability was used. Acute cytotoxicity was determined using a screening method for assessing the number of living cells in a sample (MTT test). SHED cells were sown on the materials to study the attachment of cells to materials and their migration inside the samples. Before seeding, the cells were stained with vital fluorescent dye PKH26 (red fluorescent cell linker kit, Sigma, Germany) for further visualization. Using the MTT test it was shown that they do not have cytotoxic effects. At the same time by the 8th day of the experiment in the presence of Fibro-Gide and Bio-Gide the cells showed an increase in proliferative activity by 19% and 12%, respectively compared with the control group. The cells attached and spread out on the surface of the materials and migrated into the thickness of porous Fibro-Gide and Spongostan. The in vitro study showed that the most favorable material for SHED cell culture is the collagen material Fibro-Gide with sufficient porosity, elasticity and hydrophilicity. SHED cells attach to the collagen matrix and easily penetrate into the sample, filling the entire internal space, while the proliferative capacity of the cell culture increases.

P62/SQSTM1 indirectly mediates remote multipotent mesenchymal cellsand rescues bone loss and bone marrow integrity in ovariectomized rats.

Intramuscular administration of p62/SQSTM1 (sequestosome1)-encoding plasmid demonstrated ananticancer effect in rodent models and dogsas well as a high safety profile and the first evidence of clinical benefits in humans. Also, an anti-inflammatory effect of the plasmid was reported in several rodent disease models. Yet, the mechanisms of action for the p62 plasmid remainunknown. Here, we tested a hypothesis that the p62-plasmid can act through the modulation of bone marrow multipotent mesenchymal cells (MSCs). We demonstrated that a p62 plasmid can affect MSCs indirectly by stimulating p62-transfected cells to secrete an active ingredient(s) sensed by untransfected MSCs. When we transfected MSCs with the p62-plasmid, collected their supernatant, and added it to an untransfected MSCs culture, it switched the differentiation state and prompt osteogenic responses of the untransfected MSCs. According to an accepted viewpoint, ovariectomy leads to bone pathology via dysregulation of MSCs, and restoring the MSC homeostasis would restore ovariectomy-induced bone damage. To validate our in vitro observations in a clinically relevant in vivo model, we administered the p62 plasmid to ovariectomized rats. It partially reversed bone loss and notably reduced adipogenesis with concurrent reestablishing of theMSC subpopulation pool within the bone marrow. Overall, our study suggests that remote modulation of progenitor MSCs via administering a p62-encoding plasmid may constitute a mechanism for its previously reported effects and presents a feasible disease-preventing and/or therapeutic strategy.

A Cell Culture Method for the Isolation and Study of Primary Human Dental Pulp Cells.

Primary human dental pulp cell (HDPC) cultures contain dental pulp stem cell (DPSC) populations. DPSCs are multipotent mesenchymal cells residing inside the dental pulp where they can contribute to the regenerative potential of this and other tissues throughout the body. These cells are promising tools for cell-based therapies, including regenerative endodontic procedures. HDPCs can be readily isolated and expanded from extracted teeth either by the dental tissue explant method or enzymatic digestion method. This chapter describes the explant method, whereby cells outgrow from dissected pulp tissue, to generate HDPC cultures. We also provide protocols for HDPC passaging, cryopreservation, and basic immunocytochemical characterization.

Histomorphological study of the alveolar bone in periodontitis in the experiment

A study of bone tissue regeneration under conditions of experimental periodontitis with stimulation of reparation by multipotent mesenchymal cells was carried out. The stimulating effect of the studied cell cultures on the proliferation and differentiation of periodontal osteogenic elements was revealed.

Efficiency of accelerated electron beam sterilization of a hydrogel for 3D cultivation of mesenchymal multipotent cells

Background. Hydrogels are promising for use in tissue engineering for the restoration and regeneration of various tissues, since they are able to perform the functions of bulk scaffolds, providing the formation of 3D cell structures. Population of such scaffolds with autologous or heterogeneous mesenchymal multipotent stromal cells in vitro makes it possible to localize these cells in the area of target tissues after implantation in a patient. One of the difficult tasks is the choice of the method and mode of sterilization of the hydrogel, which does not change its properties.Aim. Study of the effectiveness of hydrogel sterilization by an accelerated electron beam in various modes, changes in the structure and biocompatibility of the scaffold, to assess the prospects for its use for medical purposes, including as a platform for mesenchymal stromal cells.Materials and methods. We used a hydrogel based on 4 % solutions of sodium alginate and sodium salt of carboxymethyl cellulose, cross-linked with calcium chloride, which was developed, obtained and provided for our research by the team of the Research and Educational Center for Biomedical Engineering of the National University of Science and Technology “MISIS”. Hydrogel samples loaded with Escherichia coli, Lactobacillus acidophilus, Saccharomyces cerevisiae were subjected to electron beam treatment in the range of 5–100 kGy. After electron beam treatment of hydrogel, the presence of living microorganisms and its structure were evaluated by IR-Fourier spectroscopy, as well as the phenotype and formation of 3D structures by mesenchymal multipotent cells.Results. It was found that the treatment of hydrogels with an electron beam at a mode of 25 kGy ensures the death of microorganisms, but does not destroy the structure of the hydrogel and does not inhibit the ability to form capillary-like structures by mesenchymal multipotent cells.Conclusion. Treatment with an accelerated electron beam at a 25 kGy can be used to sterilize hydrogels to obtain bulk scaffolds for cell engineering implants.

Regulation of cardiovascular calcification by lipids and lipoproteins.

Lipids and lipoproteins have long been known to contribute to atherosclerosis and cardiovascular calcification. One theme of recent work is the study of lipoprotein (a) [Lp(a)], a lipoprotein particle similar to LDL-cholesterol that carries a long apoprotein tail and most of the circulating oxidized phospholipids. In-vitro studies show that Lp(a) stimulates osteoblastic differentiation and mineralization of vascular smooth muscle cells, while the association of Lp(a) with coronary artery calcification continues to have varying results, possibly because of the widely varying threshold levels of Lp(a) chosen for association analyses. Another emerging area in the field of cardiovascular calcification is pathological endothelial-to-mesenchymal transition (EndMT), the process whereby endothelial cell transition into multipotent mesenchymal cells, some of which differentiate into osteochondrogenic cells and mineralize. The effects of lipids and lipoproteins on EndMT suggest that they modulate cardiovascular calcification through multiple mechanisms. There are also emerging trends in imaging of calcific vasculopathy, including: intravascular optical coherence tomography for quantifying plaque characteristics, PET with a radiolabeled NaF tracer, with either CT or MRI to detect coronary plaque vulnerability. Recent work in this field includes studies of Lp(a), EndMT, and new imaging techniques.

Human Multipotent Mesenchymal Stromal Cell-Derived Extracellular Vesicles Enhance Neuroregeneration in a Rat Model of Sciatic Nerve Crush Injury.

Peripheral nerve injury remains a serious problem for medicine, with no effective method of treatment at the moment. The most prominent example of this problem is neonatal brachial plexus palsy, which results from the stretching of the brachial plexus nerves in the birth or perinatal period. Multipotent mesenchymal cells (MSCs) and the extracellular vesicles (EVs) they produce are known to have a marked neuroprotective effect in central nervous system injuries. We suggested that the use of MSCs-derived EVs may be an effective approach to the regeneration of peripheral nerves after injury. Sciatic nerve injury was modeled in rats via crushing, and then a gel containing MSCs–EVs was applied to the injured area. After 15 and 30 days, a histological, physiological, and functional assessment of nerve, dorsal root ganglia (DRG), and innervated muscles’ recovery was performed. Transplantation of EVs to the area of sciatic nerve injury significantly reduced muscle atrophy as compared to the control group. Functional recovery of the innervated muscles, as measured by the extensor postural thrust test, was revealed 30 days after the surgery. We associate the obtained results with EVs-induced neuroprotective mechanisms, which were expressed in a decrease in apoptotic neuronal death and an increase in regeneration-associated proteins NF-200 and GAP-43, as well as in DRG and damaged nerve. We suggest that the therapeutic scheme we used is efficient for the treatment of acute peripheral nervous system injuries and can be transferred to the clinics. However, additional studies are required for a more detailed analysis of neuroprotection mechanisms.

Cellular Heterogeneity Facilitates the Functional Differences Between Hair Follicle Dermal Sheath Cells and Dermal Papilla Cells: A New Classification System for Mesenchymal Cells within the Hair Follicle Niche

Mesenchymal stem cells (MSCs) are known for their self-renewal and multi-lineage differentiation potential, with these cells often being evaluated in the regulation and maintenance of specific cellular niches including those of the hair follicle. Most mesenchymal stem cells in the hair follicles are housed in the dermal papilla (DP) and dermal sheath (DS), with both niches characterized by a broad variety of cellular subsets. However, while most previous studies describing the hair follicle mesenchymal niche treated all DP and DS cells as Hair Follicle Mesenchymal Stem Cells (HF-MSCs), the high number of cellular subsets would suggest that these cells are actually too heterogenous for such a broad definition. Given this we designed this study to evaluate the differentiation processes in these cells and used this data to create a new set of classifications for DP and DS cells, dividing them into "hair follicle mesenchymal stem cells (HF-MSCs)", "hair follicle mesenchymal progenitor cells (HF-MPCs)", and "hair follicle mesenchymal functional cells (HF-MFCs)". In addition, those cells that possess self-renewal and differentiation were re-named hair follicle derived mesenchymal multipotent cells (HF-MMCs). This new classification may help to further our understanding of the heterogeneity of hair follicle dermal cells and provide new insights into their evaluation.

Mapping global trends in adipose-derived mesenchymal stem cell research: A bibliometric analysis using scopus database

Background and objectiveAdipose-derived mesenchymal stem cells (AdMSC) are multipotent adult mesenchymal cells isolated and cultured from the stromal vascular fraction derived from adipose tissue. The present study was conducted to analyze the global trends in AdMSC research using bibliometric and visual analysis tools. MethodsThe literature search was done on February 13, 2022, using appropriate keywords and inclusion-exclusion criteria from the Scopus database. The extracted data were retrospectively analyzed and visualized using Bibliometrics and R packages and VOSviewer. ResultsPreliminary analysis identified 1569 documents from the Scopus database published between 2005 and 2021. The average citations received per document was 26.51, whereas the average citations per year per document was 3.347. In addition, the selected documents had an h-index value of 90. China was the most productive country, whereas Seoul National University (South Korea) was identified as the most productive institute/university in AdMSC research. In addition, the National Natural Science Foundation of China funded the most research studies in AdMSC research. ConclusionThe findings from this study indicate a progressive increase in interest among the research community towards AdMSC, suggesting promising prospects in the coming years.

Attapulgite-doped electrospun PCL scaffolds for enhanced bone regeneration in rat cranium defects

Electrospun PCL scaffolds have been widely used for tissue engineering as they have shown great potential to mimic the structure of the natural extracellular matrix (ECM). However, the small pore size and low bioactivity of the scaffolds limit cell migration and tissue formation. In this study, PCL (polycaprolactone), PCL/PEG (polyethylene glycol), and PCL/PEG/ATP (nano-attapulgite) scaffolds were fabricated via electrospinning. To increase the porosity of the scaffolds, they were washed to remove water-soluble PEG fibers. Then the porous structure was measured using scanning electron microscopy (SEM) and atomic force microscopy (AFM), which showed an increased porosity when PEG fibers were removed in PCL/PEG and PCL/PEG/ATP scaffolds. Moreover, the mechanical properties were also analyzed in dry and wet conditions. In vitro mouse multipotent mesenchymal precursor cells were used to assess the biocompatibility of the scaffolds, and osteogenesis was analyzed using CCK-8 and real-time PCR (RT-PCR) methods. Moreover, in vivo μCT, histological and immunohistochemical analyses were conducted to evaluate new bone formation in rat cranium defect models. Washed PCL/PEG/ATP scaffolds were implanted into the cranium defects in rats for 4 or 8 weeks, better cell infiltration was observed in these scaffolds than in unwashed ones. The result demonstrated that washed PCL/PEG/ATP scaffold facilitated the differentiation of MSCs into osteoblasts compared with PCL scaffold, as proved by the increased expression of osteogenic key genes as well as Smad1, Smad4, and Smad5. Furthermore, in vivo studies demonstrated that using the ATP-doped electrospun PCL scaffold can improve the bone regeneration of rat cranium defects. Particularly, the PCL/ATP-30% scaffold has the best effect compared to the other scaffolds. The enhanced osteogenesis and bone repair were related to the PCL/ATP activated BMP/Smad signaling pathway.

Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation

Mesenchymal progenitors differentiate into several tissues including bone, cartilage, and adipose. Targeting these cells in vivo is challenging, making mesenchymal progenitor cell lines valuable tools to study tissue development. Mesenchymal stem cells (MSCs) can be isolated from humans and animals; however, obtaining homogenous, responsive cells in a reproducible fashion is challenging. As such, we developed two mesenchymal progenitor cell (MPC) lines, MPC1 and MPC2, generated from bone marrow of male C57BL/6 mice. These cells were immortalized using the temperature sensitive large T-antigen, allowing for thermal control of proliferation and differentiation. Both MPC1 and MPC2 cells are capable of osteogenic, adipogenic, and chondrogenic differentiation. Under osteogenic conditions, both lines formed mineralized nodules, and stained for alizarin red and alkaline phosphatase, while expressing osteogenic genes including Sost, Fgf23, and Dmp1. Sost and Dmp1 mRNA levels were drastically reduced with addition of parathyroid hormone, thus recapitulating in vivo responses. MPC cells secreted intact (iFGF23) and C-terminal (cFGF23) forms of the endocrine hormone FGF23, which was upregulated by 1,25 dihydroxy vitamin D (1,25D). Both lines also rapidly entered the adipogenic lineage, expressing adipose markers after 4 days in adipogenic media. MPC cells were also capable of chondrogenic differentiation, displaying increased expression of cartilaginous genes including aggrecan, Sox9, and Comp. With the ability to differentiate into multiple mesenchymal lineages and mimic in vivo responses of key regulatory genes/proteins, MPC cells are a valuable model to study factors that regulate mesenchymal lineage allocation as well as the mechanisms that dictate transcription, protein modification, and secretion of these factors.

Surgical treatment of biatrial myxoma

Cardiac myxoma is a primary tumor histologically formed by multipotent subendocardial mesenchymal cells. Myxomas account for approximately 50% of all cardiac tumors in adults. Myxomas are most commonly located in the left atrium. Very rarely, myxomas can be located in several heart chambers. Only about 100 cases of patients with myxomatous lesions of both atria have been described in the literature. In this paper, we present a successful clinical case of a young patient with biatrial myxomas.

PRIMARY EXTRACRANIAL MENINGIOMA OF THE MANDIBLE: A CASE REPORT AND LITERATURE REVIEW OF THIS RARE PRESENTATION

Meningiomas are common benign neoplasms developing within the central nervous system and arise from the meningothelial cells. Extracranial (ectopic) meningiomas are rare and may represent an extracranial extension of an intracranial meningioma or distant metastasis from a primary intracranial meningioma, or they may originate from arachnoid cells in the sheaths of the cranial nerves that are exiting the skull through the foramina or sutures. Ectopic meningiomas can also arise as true primary extracranial meningiomas originating from ectopic arachnoid lining cells or multipotential mesenchymal cells. Primary extracranial meningiomas occurring in the jaws are extremely rare, with only 11 reported cases (2 cases in the maxilla and 9 cases in the mandible) in the literature. The infrequent occurrence of this entity presenting in this unusual location of the jaws often poses a diagnostic challenge to the oral pathologist, resulting in misdiagnosis. We present the 10th mandibular case of extracranial meningioma involving the right side of the mandible in a 56-year-old female patient. The clinical and radiographic presentation, histopathologic features, and histopathologic differential and immunohistochemical findings of this case are presented. The proposed pathogenesis, treatment options, and prognosis are also discussed along with a review of the literature.