Primitive Mesenchymal Stem Cells Research Articles

Regulation of self-renewal and senescence in primitive mesenchymal stem cells by Wnt and TGFβ signaling

BackgroundThe therapeutic application of multipotent mesenchymal stem cells (MSCs) encounters significant challenges, primarily stemming from their inadequate growth and limited self-renewal capabilities. Additionally, as MSCs are propagated, their ability to self-renew declines, and the exact cellular and molecular changes responsible for this are poorly understood. This study aims to uncover the complex molecular mechanisms that govern the self-renewal of primitive (p) MSCs.MethodsWe grew pMSCs using two types of medium, fetal bovine serum (FM) and xeno-free (XM), at both low passage (LP, P3) and high passage (HP, P20). To evaluate LP and HP pMSCs, we examined their physical characteristics, cell surface markers, growth rate, colony-forming ability, BrdU assays for proliferation, telomerase activity, and potential to differentiate into three lineages. Moreover, we conducted RNA-seq to analyze their transcriptome and MNase-seq analysis to investigate nucleosome occupancies.ResultsWhen grown in FM, pMSCs underwent changes in their cellular morphology, becoming larger and elongated. This was accompanied by a decrease in the expression of CD90 and CD49f, as well as a reduction in CFE, proliferation rate, and telomerase activity. In addition, these cells showed an increased tendency to differentiate into the adipogenic lineage. However, when grown in XM, pMSCs maintained their self-renewal capacity and ability to differentiate into multiple lineages while preserving their fibroblastoid morphology. Transcriptomic analysis showed an upregulation of genes associated with self-renewal, cell cycle regulation, and DNA replication in XM-cultured pMSCs, while senescence-related genes were upregulated in FM-cultured cells. Further analysis demonstrated differential nucleosomal occupancies in self-renewal and senescence-related genes for pMSCs grown in XM and FM, respectively. These findings were confirmed by qRT-PCR analysis, which revealed alterations in the expression of genes related to self-renewal, cell cycle regulation, DNA replication, differentiation, and senescence. To understand the underlying mechanisms, we investigated the involvement of Wnt and TGFβ signaling pathways by modulating them with agonists and antagonists. This experimental manipulation led to the upregulation and downregulation of self-renewal genes in pMSCs, providing further insights into the signaling pathways governing the self-renewal and senescence of pMSCs.ConclusionOur study shows that the self-renewal potential of pMSCs is associated with the Wnt pathway, while senescence is linked to TGFβ.

Single-cell sequencing reveals activation of core transcription factors in PRC2-deficient malignant peripheral nerve sheath tumor.

SUMMARYLoss-of-function mutations in the polycomb repressive complex 2 (PRC2) occur frequently in malignant peripheral nerve sheath tumor, an aggressive sarcoma that arises from NF1-deficient Schwann cells. To define the oncogenic mechanisms underlying PRC2 loss, we use engineered cells that dynamically reassemble a competent PRC2 coupled with single-cell sequencing from clinical samples. We discover a two-pronged oncogenic process: first, PRC2 loss leads to remodeling of the bivalent chromatin and enhancer landscape, causing the upregulation of developmentally regulated transcription factors that enforce a transcriptional circuit serving as the cell’s core vulnerability. Second, PRC2 loss reduces type I interferon signaling and antigen presentation as downstream consequences of hyperactivated Ras and its cross talk with STAT/IRF transcription factors. Mapping of the transcriptional program of these PRC2-deficient tumor cells onto a constructed developmental trajectory of normal Schwann cells reveals that changes induced by PRC2 loss enforce a cellular profile characteristic of a primitive mesenchymal neural crest stem cell.

Neural stem cells derived from primitive mesenchymal stem cells reversed disease symptoms and promoted neurogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis

BackgroundMultiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). MS affects millions of people and causes a great economic and societal burden. There is no cure for MS. We used a novel approach to investigate the therapeutic potential of neural stem cells (NSCs) derived from human primitive mesenchymal stem cells (MSCs) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS.MethodsMSCs were differentiated into NSCs, labeled with PKH26, and injected into the tail vein of EAE mice. Neurobehavioral changes in the mice assessed the effect of transplanted cells on the disease process. The animals were sacrificed two weeks following cell transplantation to collect blood, lymphatic, and CNS tissues for analysis. Transplanted cells were tracked in various tissues by flow cytometry. Immune infiltrates were determined and characterized by H&E and immunohistochemical staining, respectively. Levels of immune regulatory cells, Treg and Th17, were analyzed by flow cytometry. Myelination was determined by Luxol fast blue staining and immunostaining. In vivo fate of transplanted cells and expression of inflammation, astrogliosis, myelination, neural, neuroprotection, and neurogenesis markers were investigated by using immunohistochemical and qRT-PCR analysis.ResultsMSC-derived NSCs expressed specific neural markers, NESTIN, TUJ1, VIMENTIN, and PAX6. NSCs improved EAE symptoms more than MSCs when transplanted in EAE mice. Post-transplantation analyses also showed homing of MSCs and NSCs into the CNS with concomitant induction of an anti-inflammatory response, resulting in reducing immune infiltrates. NSCs also modulated Treg and Th17 cell levels in EAE mice comparable to healthy controls. Luxol fast blue staining showed significant improvement in myelination in treated mice. Further analysis showed that NSCs upregulated genes involved in myelination and neuroprotection but downregulated inflammatory and astrogliosis genes more significantly than MSCs. Importantly, NSCs differentiated into neural derivatives and promoted neurogenesis, possibly by modulating BDNF and FGF signaling pathways.ConclusionsNSC transplantation reversed the disease process by inducing an anti-inflammatory response and promoting myelination, neuroprotection, and neurogenesis in EAE disease animals. These promising results provide a basis for clinical studies to treat MS using NSCs derived from primitive MSCs.

Loss of PRC2 Enforces a Mesenchymal Neural Crest Stem Cell Phenotype in NF1-Deficient Cancer Through Activation of Core Transcription Factors

Genetic alterations that result in the dysregulation of polycomb repressive complex 2 (PRC2) are common features of multiple cancer types. Loss-of-function mutations in the PRC2 genes, SUZ12 or EED, occur at high frequency in malignant peripheral nerve sheath tumors (MPNST), a clinically aggressive sarcoma that arises from NF1-deficient Schwann cells. To define the oncogenic mechanisms mediated by PRC2 loss, we used engineered MPNST model systems that dynamically reassemble a competent PRC2 coupled with single cell sequencing from clinical samples to evaluate the transcriptomic and epigenetic consequences of PRC2 loss. We discovered a two-pronged oncogenic process; first, PRC2 loss leads to remodeling of bivalent chromatin and the enhancer landscape of the tumor cell. These epigenetic changes result in the upregulation of developmentally regulated transcription factors, including FOXC1, which enforce a transcriptional circuit that is a core vulnerability of the cell. Second, PRC2 loss reduces type I interferon signaling and antigen presentation as a downstream consequence of hyperactivated Ras signaling and its crosstalk with STAT and IRF transcription factors. Mapping of the transcriptional program of these PRC2-deficient tumor cells onto a constructed developmental trajectory of the developing neural crest stem cell revealed that changes induced by PRC2 loss enforced a cellular profile characteristic of a primitive mesenchymal neural crest stem cell.

Silencing KIF18B enhances radiosensitivity: identification of a promising therapeutic target in sarcoma.

BackgroundSarcomas are rare heterogeneous tumours, derived from primitive mesenchymal stem cells, with more than 100 distinct subtypes. Radioresistance remains a major clinical challenge for sarcomas, demanding urgent for effective biomarkers of radiosensitivity.MethodsThe radiosensitive gene Kinesin family member 18B (KIF18B) was mined through bioinformatics with integrating of 15 Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database. We used radiotherapy-sh-KIF18B combination to observe the anti-tumour effect in sarcoma cells and subcutaneous or orthotopic xenograft models. The KIF18B-sensitive drug T0901317 (T09) was further mined to act as radiosensitizer using the Genomics of Drug Sensitivity in Cancer (GDSC) database.FindingsKIF18B mRNA was significantly up-regulated in most of the subtypes of bone and soft tissue sarcoma. Multivariate Cox regression analysis showed that KIF18B high expression was an independent risk factor for prognosis in sarcoma patients with radiotherapy. Silencing KIF18B or using T09 significantly improved the radiosensitivity of sarcoma cells, delayed tumour growth in subcutaneous and orthotopic xenograft model, and elongated mice survival time. Furthermore, we predicted that T09 might bind to the structural region of KIF18B to exert radiosensitization.InterpretationThese results indicated that sarcomas with low expression of KIF18B may benefit from radiotherapy. Moreover, the radiosensitivity of sarcomas with overexpressed KIF18B could be effectively improved by silencing KIF18B or using T09, which may provide promising strategies for radiotherapy treatment of sarcoma.FundingsA full list of funding can be found in the Funding Sources section.

Human Chorionic Gonadotropin Improves the Proliferation and Regenerative Potential of Bone Marrow Adherent Stem Cells and the Immune Tolerance of Fetal Microchimeric Stem Cells In Vitro.

Nongonadal tissues express luteinizing hormone-chorionic gonadotropin receptors (LHCG-R) which are essential for their growth during fetal development. Adult mesenchymal stem/stromal cells (MSCs) have been shown to express functional LHCG-R outside pregnancy conditions, making them susceptible to hCG stimulation. In the present study we tested the effect of hCG treatment on bone marrow (BM) derived adherent stem cells in vitro, isolated from a parous women, mother of male sons, in order to evaluate its effect on maternal MSCs and in the same time on fetal microchimeric stem cells (FMSCs), to better understand the outcomes of this safe and affordable treatment on cell proliferation and expression of pluripotency genes. Our study highlights the beneficial effects of hCG exposure on gene regulation in bone marrow adherent stem cells through the upregulation of pluripotency genes and selection of more primitive mesenchymal stem cells with a better differentiation potential. Validation of these effects on MSCs and FMSCs long after parturition in vivo represents a close perspective as it could set the premises of a new mobilization strategy for the stem cell transplantation procedures in the clinical setting.

Savremena radioterapija rabdomiosarkoma dece

Rhabdomyosarcoma is the most common soft tissue sarcoma among children and represents half of all soft tissue sarcomas. The tumor is derived from primitive mesenchymal stem cells which develop into striated muscle and common sites of occurrence are the head and neck region, genitourinary tract and extremities. Treatment is multimodal and includes surgery, radiotherapy and chemotherapy. Application of combined treatment led to significant improvement in treatment outcome. Due to long-term survival, great importance is given to the expected treatment complications. Therapy for pediatric rhabdomyosarcoma requires a delicate balance between the need to intensify therapy for certain group of patients and the desire to reduce potentially toxic therapy and risk for secondary malignancies for patients with good prognosis. Radiotherapy plays an important role in local control of disease and is performed in nearly all patients. Since it is applied to organs and tissues that are in growth and development phase, radiotherapy in childhood has its own specificity and represents greater challenge in relation to the treatment of adult patients. The use of modern radiotherapy techniques ensures excellent local control of disease with better sparing of normal surrounding tissues which reduces radiotherapy toxicity and preserves quality of life of treated children.

Adult Stem Cells Based Therapies in Veterinary Medicine

Research into adult mesenchymal stem cells (MSCs) and their therapeutic potential for treating various diseases is nowadays on the rise, not only in human, but also in veterinary medicine. MSCs are easy to collect from most tissues and relatively safe with no ethical concerns. They can be used in veterinary medicine as autologous or allogenic cell-based therapies for orthopaedic injuries, cardiovascular, muscular and neurodegenerative disorders and wound healing. The therapeutic action of MSCs lies either in their differentiation towards cells which need to be replaced, or in their immunomodulatory and paracrine effects through which they support recovery of various tissues. Regarding these pro-regenerative properties considerable attention has to be paid to proper matching of MSC sources with respect to the nature of the diseases needing to be cured. Overall data indicate that particularly the umbilical cord MSC (UC MSC) therapy which involves the most primitive MSCs may bring considerable benefits to patients with a wide range of diseases. This review describes the pro-regenerative potential of MSCs with the main focus on advances in UC MSCs based therapy in veterinary medicine.

Expression of HIF‑1α in cycling stretch‑induced osteogenic differentiation of bone mesenchymal stem cells.

During orthodontic treatment, mechanical force is applied to the teeth, and following a series of complex metabolism changes, the position of the teeth in the alveolar bone change. This process is closely associated with primitive bone mesenchymal stem cells (BMSCs), which may differentiate into osteoblasts precursor cell. A hypoxic microenvironment may be caused by orthodontic mechanical forces between the alveolar bone and the root. Hypoxia-inducible factor 1α (HIF-1α) is a specific receptor that adapts to a hypoxic environment. The present study was designed to investigate whether HIF-1α was involved in the osteoblastic differentiation of BMSCs induced by cyclic tensile stress. During this process, HIF-1α mRNA and protein expression were detected using a reverse transcription-quantitative polymerase chain reaction and western blotting. It was revealed that alkaline phosphatase activity increased in a time-dependent manner in three different stretching strength groups, which indicates that cyclic stretch promotes the osteogenic differentiation of BMSCs. The optimal force stage of osteogenesis was an unexpected discovery, which will provide theoretical guidance for selecting the most suitable orthodontic force for tooth movement in clinical orthodontic treatment. Most importantly, all experiments revealed that HIF-1α mRNA and protein were significantly increased following stretching treatment in BMSCs. It was therefore concluded that HIF-1α may be involved in BMSCs modulating osteogenic metabolism during exposure to cyclic stretch and a hypoxic microenvironment, which may prove useful for the reconstruction of a jaw during orthodontic treatment.

Involvement of mTOR-autophagy in the selection of primitive mesenchymal stem cells in chitosan film 3-dimensional culture

Mesenchymal stem cells (MSCs) in conventional monolayer culture are heterogeneous and contain a significant portion of senescent cells. MSCs cultured on chitosan film form 3-dimenional spheres, increase in stemness and differentiation capability; however, the underlying mechanisms remain elusive. We first demonstrate chitosan film culture induces apoptosis at 2 days, with specificity in late senescent cells. Especially in senescent cells, chitosan film culture activates mTOR, which activates S6K/S6/4E-BP1 to enhance fibronection synthesis and peripheral dead cell attachment, and phosphorylates ULK1 at S757 to further inactivate ULK1, LC3A and autophagy, thereby inducing apoptosis. Combination of chitosan film culture with mTOR inhibition prevents peripheral dead cell attachment, thereby further increasing pluripotent gene expression, in vitro osteogenesis and in vivo bone formation. These data successfully figure out the role of mTOR signaling in chitosan film culture and develop a method by combination of rapamycin treatment for promoting stemness and differentiation capability in MSCs.

Abstract 3003: Exome analysis of known hereditary cancer genes in 122 children with rhabdomyosarcoma

Abstract Introduction. Rhabdomyosarcoma (RMS) accounts for 5% of all pediatric cancer and is the most prevalent soft tissue tumor in childhood and adolescents. RMS is thought to arise from primitive mesenchymal stem cells directed towards myogenesis. Between 7-33% of RMS cases arise from a hereditary cancer syndrome, like LFS or NF1. We analyzed germline genetic variants in hereditary cancer genes in 122 children with RMS. Methodology. In 122 children with RMS and 1001 cancer-free adults, we examined germline exome data to determine the frequency of genetic variants in 51 cancer genes known to underlie syndromes associated with RMS. DNA was extracted from blood or buccal cells using standard methods. Exome enrichment was performed with NimbleGen SeqCap EZ Human Exome Library v3.0+UTR, on an Illumina HiSeq. Annotation of each exome variant was performed using a custom software pipeline. We evaluated all variants that passed quality controls with a population minor allele frequency (MAF) <0.1%. The cataloging of the variants was based on the ACMG classification as pathogenic (P), likely pathogenic (LP), or variable of unknown significance. Results We compared the age, gender, histologic type and localization of the primary RMS of the patients with and without P/LP variants in the 51 genes. In the patients without P/LP variants, the mean age of diagnosis was 5 years and the most frequent site of diagnosis was head and neck. In the group with P/LP variants, the mean age of diagnosis was 10 years, and the most frequent site was pelvis. In the 51 genes that were analyzed we found 9 P and 12 LP variants in 15 genes: TP53, ATM, MSH6, PMS, DICER1, FANCA, RECQL4, PTEN, WRN, RB1, BUB1B, RET, APC, FANCM and TSC2; genes with 2 variants include WRN, PTEN, BUB1B, FANCA and RET. Most of the variations were stopgain, follow by missense, frameshift insertion and splicing genetic variations. Ten of this genes are associated with an autosomal dominant pattern of inheritance. In one 15-year-old female patient with an alveolar RMS in the paraspinal area we found P/LP variants in PTEN and PMS2. The frequency of P/LP variants in cases was 16% and 3% in controls. Conclusions. To our knowledge, this is the first study where multiple germline variation where analyses in children with RMS. We found P/LP variation in 16% of all the cases (pending orthogonal confirmation); the mean age of diagnosis was 10 years old and their primary tumor site was in the pelvis (50%). Identification of P/LP variation in genes underlying RMS-associated syndromes has implications for follow-up, screening and management of these patients and their families. We acknowledge the Children’s Oncology Group in helping to assemble the RMS cohort. Citation Format: Talia Wegman-Ostrosky, Rajesh Patidar, Sivasish Sindiri, Jack Shern, Douglas S. Hawkins, Daniel Catchpoole, Jun S. Wei, Stephen Skapek, Javed Khan, Douglas R. Stewart. Exome analysis of known hereditary cancer genes in 122 children with rhabdomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3003. doi:10.1158/1538-7445.AM2017-3003

Biologic and Clinical Aspects of Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a muscle-derived tumor and is the most common pediatric soft tissue sarcoma representing 5% of all childhood cancers. Statistically, soft tissue sarcomas account for approximately 10% of all cancers in children, of which more than half of these tumors are RMS. Thus, RMS is a major clinical problem in pediatric oncology. RMS is caused by a disruption in the pathway of primitive mesenchymal stem cells directed towards myogenesis. In most cases of patients diagnosed with RMS there is a genetic or chromosomal alteration involved. In past few years there have been discoveries of more therapeutic approaches that has improved the quality of life in RMS patients and has resulted in a better survival rate in this population from 25% to 60%. However, Additional researches and clinical trials are needed in order to minimize the devastating consequences of the pediatric cancer including RMS. In the current mini review we will briefly discuss current knowledge in RMS focusing on most common biological and clinical aspects of the disease.

The animal-dependent risk factors in canine osteosarcomas.

Canine osteosarcoma (OSA) is a malignant neoplastic tumor, which develops from the primitive mesenchymal stem cell, that has or can acquire the capacity to produce neoplastic osteoid with possible neoplastic bone formation. Predisposition of some dog breeds to OSA indicates genetic background of oncogenesis. The aim of the study was to characterize animal-dependent risk factors for canine osteosarcoma development in Poland. The study was conducted on canine patients diagnosed cytologically or histopathologically as having OSA, and data on age, breed, sex, as well as tumor location and character were recorded. No sex predisposition to OSA was observed, mongrels were significantly underrepresented. Large and giant dogs accounted for 47% and 35% of all pedigree dogs, respectively, and both proved predisposed to OSA. A vast majority of OSA developed in the skeleton (appendicular skeleton was more commonly affected than axial skeleton), soft tissues were affected less often. Rottweiler dogs are strongly predisposed to OSA, suggesting that the genetic background is involved in the tumor development, and indicates that dogs of this breed are a promising object for further studies on OSA pathogenesis.

The Management Challenges in an Unusual Case of Primary Osteosarcoma of the Rib in an Adult Patient.

Primary osteosarcomas are derived from primitive bone-forming mesenchymal stem cells and most often originate in the metaphysis of the long bones of children and adolescents, but it occurs very rare in adults. Approximately 10% of osteosarcomas are located in the flat bones, pelvis being the main site. Involvement of flat bones like rib may be seen as a metastatic process or secondary to chemotherapy, but a primary osteosarcoma rib is extremely rare. Osteosarcoma originating from such rare sites poses numerous diagnostic and therapeutic challenges, and we report one such case in a 24-year-old male patient. Our case highlights the fact that osteosarcoma of the rib, although rare, should be considered in the differential diagnosis of primary malignant neoplasms of the rib even in the adult population. Further, early prompt diagnosis and aggressive multimodality management are cornerstones of management and will help improve the survival outcomes.

Pre-transplant osteogenic induction promotes primitive mesenchymal stem cells’ functional secretion and healing efficacy

Pre-transplant osteogenic induction promotes primitive mesenchymal stem cells’ functional secretion and healing efficacy

Effects of three-dimensional culture on cell phenotype and hematopoietic cytokine expression of umbilical cord mesenchymal stem cells

This study was aimed to investigate the change of cell phenotype and the expression of hematopoiesis associated cytokines in umbilical cord mesenchymal stem cells (UC-MSC) in three-dimensional (3-D) system. MSC were isolated from umbilical cord, and then cultured in 2-D and 3-D system respectively. The phenotype of MSC was detected by flow cytometry; the angiogenic capability of MSC cultured in 2-D and 3-D syitem was assessed using in vitro capillary formation assay. The cytokine expression of MSC in two kinds of culture conditions was measured by real-time PCR. The results showed that MSC were successfully isolated from umbilical cord. Flow cytometry showed that the percentage of CD31, CD133 and CD271 expressed in endothelial cells, endothelial progenitor cells and primitive mesenchymal stem cells increased significantly in 3-D culture conditions, as compared to 2-D system. Capillary formation assay showed that the angiogenic capability of UC-MSC was greatly enhanced. Quantitative PCR showed that the expression of β-actin was upregulated in 3-D system. The expression of some cytokines associated with hematopoiesis, such as G-CSF, LIF, SCF, IL-1α, IL-1β, IL-3, IL-7 and IL-11, increased, especially for LIF, IL-3, IL-7. The expression of IL-10 associated with immune regulation also increased. The expression of SDF-1, IL-6 slightly decreased, but without significant difference. It is concluded that expression of CD31, CD133 and CD271 increases in 3-D system, the angiogenic capability of UC-MSC enhances and the expression of hematopoiesis-associated cytokines in UC-MSC increases in 3-D system.

Human Wharton's jelly stem cells, its conditioned medium and cell-free lysate inhibit the growth of human lymphoma cells.

Several groups have reported that primitive mesenchymal stem cells from the gelatinous matrix of the Wharton's jelly of the human umbilical cord (hWJSCs) possess tumoricidal properties and inhibit the growth of solid tumours such as human mammary carcinoma, ovarian carcinoma and osteosarcoma. This unique characteristic led to the hypothesis that hWJSCs serve as a natural defence against migrating cancer cells from mother to fetus thus explaining why tumorigenesis in the fetus is rare. However, it is not known whether non-solid malignant hematopoietic cells are also inhibited by hWJSCs and what the exact tumoricidal mechanisms are. We therefore evaluated the influence of hWJSCs and its extracts on Burkitt's lymphoma cells. Cell proliferation (BrdU and Ki67+), viability (MTT) and cell death (Annexin V-Propidium iodide and live/dead) assays showed significant inhibition of lymphoma cell growth after 48h exposure to hWJSCs or its extracts compared to controls. Increased cell death was observed at sub-G1 and S and decreased proliferation at G2/M phases of the mitotic cycle. Superoxide dismutase and hydrogen peroxide activity were significantly increased and glutathione peroxidase significantly decreased in treated lymphoma cells. Time lapse imaging and confocal z-stack images showed yellow fluorescent in situ hybridization (FISH) signals of lymphoma cell Y chromosomes within the cytoplasm of female red labelled hWJSCs. We hypothesize that the growth of lymphoma cells is inhibited by the molecules secreted by hWJSCs that use oxidative stress pathways to induce cell death followed by engulfment of the apoptotic remains of the lymphoma cells by the hWJSCs.

Intracranial Dural Based Malign Mesenchymal Neoplasm: Case Report

Dural based sarcoma is a rare aggressive neoplasm arising from the multipotent primitive mesenchymal stem cells of the dura. A 61-year-old male patient presented with complaints of loss of visual acuity in his right eye for 1 week. Neuroimaging revealed a tumour located at the right temporal lobe. The mass was dural-based. Three years ago dural based lesion was seen. In that period radiological diagnosis was meningioma. Within three years, the lesion has grown and radiologically presumed meningioma view has been disappeared. After surgical resection of the mass pathological diagnosis of primary dural based sarcoma was made. As in soft tissue sarcomas, diagnosis is mainly based on light microscopy, while immunohistochemistry can improve accuracy of diagnosis. In this article we would like to highlight two things: one is dural sarcoma and meningioma cannot be distinguished radiologically, and the other is the patient's three-year history

Differentiation of Human Umbilical Cord Lining Membrane-Derived Mesenchymal Stem Cells into Hepatocyte-Like Cells

Background. Mesenchymal stem cells (MSCs), isolated from bone marrow, adipose tissue, and umbilical cord tissue, have been known to differentiate into hepatocyte-like cells. MSCs can also be easily obtained from umbilical cord lining membrane (CLMSCs). CLMSCs are more primitive MSCs than those isolated from other tissue sources. Objectives. The aim of this study was to investigate the in vitro differentiation of CLMSCs into hepatocyte lineage. Materials and Methods. In this study, CLMSCs were isolated through a tissue attachment method. Cells were characterized for expression of MSC-specific markers and differentiation potency. CLMSCs were induced to differentiate into hepatocytes by a simple two-step protocol. Differentiated cells were examined for the expression of hepatocyte-specific markers and hepatocyte functions. Results. CLMSCs expressed MSC-specific markers and differentiated into adipocytes and osteoblasts. RT-PCR, real-time qRT-PCR, Western blot, and immunocytochemistry analyses demonstrated that differentiated CLMSCs, having hepatocyte-like morphology, expressed several liver-specific markers, such as ALB, AFP, CK18, and CK19, at both mRNA and protein levels following hepatocyte differentiation. Furthermore, periodic acid-Schiff staining and low-density lipoprotein (LDL) uptake assay showed that differentiated cells could store glycogen and uptake LDL. Conclusion. This study demonstrated that CLMSCs can differentiate into functional hepatocyte-like cells. CLMSCs can serve as a favorable cell source for tissue engineering in the treatment of liver disease.

Meningeal osteochondroma simulating meningioma with metaplastic change: a rare golf-ball-like lesion of non-meningothelial mesenchymal origin

Non-meningothelial mesenchymal tumors of the central nervous system (CNS), including those originating from the meninges, histologically correspond to tumors of soft tissue or bone. These individual entities arising from the meninges are rare, and probably have their origin in the multipotent primitive mesenchymal stem cells of the dura. Though it is a common bone tumor, the meningeal origin of osteochondroma has only very rarely been reported. We describe a case of a 35-year-old female with a well-demarcated, golf-ball-like osteochondroma of meningeal origin which was enucleated en bloc on craniotomy. Such a lesion can resemble a meningioma that exhibits metaplastic (osseous) change on imaging. However, provided that there is clinico-radiological awareness of such tumors, magnetic resonance imaging (MRI) can guide the way to this rare differential diagnosis, as it reflects the pathologic appearance of osteochondroma and allows the thickness of the cartilage cap to be estimated in order to check for rare malignant change. Complete excision along with the cartilage cap usually offers a favorable prognosis without recurrence.