الملخص
Stem cells are undifferentiated cells that can be distinguished from others by their ability to self-renew and to differentiate into new specific cell types. Mesenchymal stem cells (MSC) are adult stem cells that can be obtained from different sources, such as adipose tissue, bone marrow, dental pulp, and umbilical cord. They can either replicate, originating new identical cells, or differentiate into cells of mesodermal origin and from other germ layers. MSC have been studied as new tools for regenerative therapy. Although encouraging results have been demonstrated, MSC-based therapies still face a great barrier: the difficulty of isolating these cells from heterogeneous environments. MSC are currently characterized by immunolabelling through a set of multiple surface membrane markers, including CD29, CD73, CD90 and CD105, which are also expressed by other cell types. Hence, the present work aimed to identify new specific biomarkers for the characterization of human MSC using DNA aptamers produced by the SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technique. Our results showed that MSC from different origins bound to DNA candidate aptamers, that is, DNA or RNA oligonucleotides selected from random libraries that bind specifically to biological targets. Aptamer-bound MSC could be isolated by fluorescenceactivated cell sorting (FACS) procedures, enhancing the induction of differentiation into specific phenotypes (chondrocytes, osteocytes and adipocytes) when compared to the whole MSC population. Flow cytometry analyses revealed that candidate aptamers bound to 50% of the MSC population from dental pulp and did not present significant binding rates to human fibroblasts or lymphocytes, both used as negative control. Moreover, immunofluorescence images and confocal analyses revealed staining of MSC by aptamers localized in the surfacemembrane of these cells. The results also showed internal staining of human monocytes by our investigated aptamers. A non-specific control aptamer (CNTR APT) obtained from the random pool was then utilized to compare the specificity of the aptamers bound to the analyzed non-apoptotic cells, showing no staining for MSC. However, 40% of the monocytes bound to the CNTR APT. Normalized data based on the cells bound to candidate aptamers compared to those bound to the CNTR APT, revealed a 10 to 16-fold higher binding rate for MSC against 2-fold for monocytes. Despite its low specificity, monocyte-aptamer binding occurs probably due to the expression of shared markers with MSC, since monocytes are derived from hematopoietic stem cells and are important for the immune system ability to internalize/phagocyte external molecules. Given that, we performed a pull-down assay followed by mass spectrometry analysis to detect which MSC-specific protein or other target epitope not coexpressed by monocytes or the CNTR APT would bind to the candidate aptamer. Distinguishing between MSC and monocyte epitopes is important, as both cells are involved in immunomodulatory effects after MSC transplantations. ADAM17 was found to be a target of the APT10, emerging as a possible biomarker of MSC, since its involvement in the inhibition of the TGF signaling cascade, which is responsible for the differentiation of MSC. Thus, MSC with a higher stemness profile should overexpress the protein ADAM17, which presents a catalytic site with affinity to APT10. Another target of Apt 10 is VAMP3, belonging to a transmembrane protein complex that is involved in endocytosis and exocytosis processes during immune and inflammatory responses. Overall, proteins identified as targets of APT10 may be cell surface MSC biomarkers, with importance for MSC-based cell and immune therapies
Células tronco são células indiferenciadas que podem ser distinguidas de outros tipos celulares por meio da habilidade de se auto renovarem e de se diferenciarem em novos tipos celulares. Células tronco mesenquimais (MSC) são células tronco adultas encontradas em diferentes tecidos como tecido adiposo, polpa de dente e cordão umbilical. Estas células podem se autodividir em células idênticas ou se diferenciarem em células de origem mesodermal. Estas células têm sido estudadas em novas aplicações que envolvem terapia regenerativas. Embora resultados encorajadores tenham sido demonstrados, terapias que utilizam MSC ainda encontram uma grande barreira: a dificuldade no isolamento destas células a partir de um ambiente heterogêneo. MSC são caracterizadas por populações positivas em ensaios de imunomarcação para os epítopos membranares CD29, CD73, CD90 e CD105, presentes também em outros tipos celulares. Assim, o presente trabalho tem o objetivo de identificar novos biomarcadores de MSC de origem humana, utilizando aptâmeros de DNA produzidos pela técnica SELEX (Systematic Evolution of Ligands by EXponential Enrichment) como ferramenta. Nossos resultados mostraram que MSC de diferentes origens ligam-se a aptâmeros (oligonucleotídeos de DNA ou RNA que atuam como ligantes específicos de alvos moleculares) de DNA candidatos que atuam no isolamento de MSC por meio da técnica FACS de separação celular, promovendo uma maior indução de diferenciação em células específicas (condrócitos, osteócitos e adipócitos) comparada com a população total de MSC. Análises de citometria de fluxo mostraram que os aptâmeros candidatos se ligam a 50% das MSC de polpa de dente e não apresentam taxa de ligação significante para fibroblastos e linfócitos de origem humana - utilizados como controles negativo. Além domais, imagens de imunofluorescência e confocal mostraram ligação na superfície da membrana de MSC e a marcação interna de monócitos a estes aptâmeros. Portanto, um aptâmero controle (CNTR APT) foi utilizado para comparar a especificidade dos aptâmeros ligados a células viáveis, mostrando a não ligação deste aptâmero a MSC. Porém, 40% da população de monócitos ligou-se ao CNTR APT. Uma normalização baseada na comparação entre as taxas de ligação entre células ligadas com aptâmeros candidatos e o aptâmero controle gerou uma taxa de especificidade entre 10-16 vezes maior para MSC contra 2,5 vezes para os monócitos. Deste modo, embora os resultados tenham mostrado uma taxa de ligação entre monócitos e aptâmeros, as MSC ligadas aos aptâmeros candidatos possuem uma maior taxa de especificidade devido a uma maior presença de antígenos que são expressos em ambas as células. Um ensaio de Pull Down seguido de espectrometria de massas foi utilizado para a identificação de biomarcadores que se ligariam aos aptâmeros candidatos, e que não seriam co-expressos por monócitos e por antígenos ligados ao aptâmero controle. Deste modo, a proteína ADAM17 foi identificada nas amostras de APT10 ligadas às MSC. Tal proteína está relacionada à inibição de uma cascata de sinalização da família de proteínas TGF, responsável pela diferenciação de MSC. Assim, MSC com maior potencial tronco deveriam expressar ADAM17 em maior quantidade. Tal proteína apresenta um sítio catalítico que demonstra interagir com o APT10, de acordo com predição Docking entre proteína e DNA. Foi identificada também, a proteína VAMP3, que pertence a um complexo proteico transmembranar responsável pelos processos de endocitose e exocitose, e que podem ter um papel importante na liberação de citocinas e outras moléculas relacionadas às respostas imune e inflamatórias. Deste modo, o APT10 identificou proteínas importantes que devem estar relacionas com a melhora de imunoterapias que utilizam MSC
الموضوعات
Stem Cells , Biomarkers/analysis , SELEX Aptamer Technique/instrumentation , Mesenchymal Stem Cells/classification , ADAM17 Protein/pharmacology , Patient Isolation , Mass Spectrometry/methods , Staining and Labeling/methods , Transplantation/adverse effects , Umbilical Cord , DNA/agonists , Transforming Growth Factors/agonists , Cell Separation/instrumentation , Cytokines/adverse effects , Adipocytes/metabolism , Chondrocytes/classification , Scientists for Health and Research for Development , Adult Stem Cells/classification , Fibroblasts/chemistry , Flow Cytometry/instrumentation , Germ Layers , Antigens/adverse effectsالملخص
It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a "dose effect". Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development.
الموضوعات
Animals , Mice , Activins , Metabolism , Cells, Cultured , Embryonic Development , Germ Layers , Metabolism , Pluripotent Stem Cells , Cell Biology , Metabolismالملخص
Benign teratomas of the thyroid are very rare in adolescence and adults. In this review, we report a case of 14-year-old Korean girl with huge neck mass. She presented with anterior neck enlargement and compression symptom which was rapidly aggravated in 2 months. In physical examination, enlarged and firm right thyroid lobe was palpated and laboratory test of thyroid function was normal. In ultrasonography, right lobe was mainly occupied with a solid nodule size of 44×23×25 mm, showing markedly inhomogeneous hypoechogenicity. As fine needle aspiration cytology was non-diagnostic, lobectomy was done. Histological examination demonstrated that the tumor is benign thyroid teratoma composed of tissue from all three germ layers. When large thyroid nodule is detected in adolescence and malignancy could not be ruled out, final diagnosis should be made with surgical resection. And we should at least attentive for possibility of teratomas when ultrasonographic findings are suspicious.
الموضوعات
Adolescent , Adult , Female , Humans , Biopsy, Fine-Needle , Diagnosis , Germ Layers , Neck , Physical Examination , Teratoma , Thyroid Gland , Thyroid Nodule , Ultrasonographyالملخص
Incomplete development and severe malformation of the heart result in miscarriage of embryos because of its malfunction as a pump for circulation. During cardiogenesis, development of the heart is precisely coordinated by the genetically-primed program that is revealed by the sequential expression of transcription factors. It is important to investigate how spatial allocation of the heart containing cardiomyocytes and other mesoderm-derived cells is determined. In addition, the molecular mechanism underlying cardiomyocyte differentiation still remains elusive. The location of ectoderm-, mesoderm-, and endoderm-derived organs is determined by their initial allocation and subsequent mutual cell-cell interactions or paracrine-based regulation. In the present work, we provide an overview of cardiac development controlled by the germ layers and discuss the points that should be uncovered in future for understanding cardiogenesis.
الموضوعات
Female , Humans , Pregnancy , Abortion, Spontaneous , Cilia , Embryonic Development , Embryonic Structures , Germ Layers , Heart , Myocytes, Cardiac , Transcription Factors , Zebrafishالملخص
iPS cells are derived from somatic cells via transduction and expression of selective transcription factors. Both viral-integrating (like retroviral) and non-integrating (like, mRNA or protein-based) techniques are available for the production of iPS cells. In the field of dentistry, iPS cells have been derived from stem cells of apical papilla, dental pulp stem cells, and stem cells from exfoliated deciduous teeth, gingival and periodontal ligament fibroblasts, and buccal mucosa fibroblasts. iPS cells have the potential to differentiate into all derivatives of the 3 primary germ layers i.e. ectoderm, endoderm, and mesoderm. They are autogeneically accessible, and can produce patient-specific or disease-specific cell lines without the issue of ethical controversy. They have been successfully tested to produce mesenchymal stem cells-like cells, neural crest-like cells, ameloblasts-like cells, odontoblasts-like cells, and osteoprogenitor cells. These cells can aid in regeneration of periodontal ligament, alveolar bone, cementum, dentin-pulp complex, as well as possible Biotooth formation. However certain key issues like, epigenetic memory of iPS cells, viral-transduction, tumorgenesis and teratoma formation need to be overcome, before they can be successfully used in clinical practice. The article discusses the sources, pros and cons, and current applications of iPS cells in dentistry with an emphasis on encountered challenges and their solutions.
الموضوعات
Cell Line , Dental Cementum , Dental Papilla , Dentistry , Ectoderm , Endoderm , Epigenomics , Fibroblasts , Germ Layers , Induced Pluripotent Stem Cells , Memory , Mesoderm , Mouth Mucosa , Periodontal Ligament , Regeneration , RNA, Messenger , Stem Cells , Teratoma , Tooth, Deciduous , Transcription Factorsالملخص
Human embryology is the study of development from a single cell to a baby in 9 months. Implantation occurs at the end of the first week of development. The second week of development is known as the week of 2's. Gastrulation, the most characteristic event occurring in the third week, establishes three germ layers composed of ectoderm, mesoderm, and endoderm. The three germ layers and neural crest cells lead to the development of their own tissues and organs during the embryonic period, which extends from the third to the eighth week. Major congenital malformations occur in the embryonic period. The fetal period, from the third month to the day of birth, is the time for maturation of tissues and organs, and growth of the body. Because of the close relationship between embryology and congenital abnormalities, knowledge of human development is essential to assess the effects on the embryo when the mother has been exposed to teratogens. This paper briefly reviews the normal embryonic development and associated congenital malformation.
الموضوعات
Female , Humans , Pregnancy , Congenital Abnormalities , Ectoderm , Embryology , Embryonic Development , Embryonic Structures , Endoderm , Gastrulation , Germ Layers , Human Development , Mesoderm , Mothers , Neural Crest , Neurulation , Parturition , Teratogensالملخص
Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases. To determine the pathological mechanism of ALS, we generated mouse iPS (miPS) cells from experimental ALS transgenic mice and control mice and characterized the cells using molecular biological methods. The generated miPS cells expressed many pluripotent genes and differentiated into three germ layers in vitro and in vivo. Motor neurons derived from ALS-related miPS cells recapitulated the pathological features of ALS. The ALS-model motor neurons showed SOD1 aggregates, as well as decreased cell survival rate and neurite length compared with wild-type motor neurons. Our study will be helpful in revealing the mechanism of motor neuronal cell death in ALS.
الموضوعات
Animals , Mice , Amyotrophic Lateral Sclerosis , Brain , Cell Death , Cell Survival , Germ Layers , In Vitro Techniques , Induced Pluripotent Stem Cells , Mice, Transgenic , Motor Neurons , Neurites , Neurodegenerative Diseases , Spinal Cord , Superoxide Dismutaseالملخص
A mature teratoma is a tumor composed of normal derivatives of all three germ layers, and usually occurs in ovaries, testes, or mediastinum. Mature teratoma of the gastrointestinal tract occurs less frequently, and case reports of primary mature teratoma of the rectum have not been published much. Here, we report a 65-year-old woman patient presented with lower abdominal discomfort. Colonoscopy revealed a pedunculated polypoid tumor arising from the rectum with hairs on its surface, and endoscopic ultrasound revealed an exophytic pattern bulging from the serosa. The tumor was removed surgically and confirmed histologically as a benign, primary mature teratoma of the rectum.
الموضوعات
Aged , Female , Humans , Colonoscopy , Gastrointestinal Tract , Germ Layers , Hair , Mediastinum , Ovary , Rectum , Serous Membrane , Teratoma , Testis , Ultrasonographyالملخص
<p><b>OBJECTIVE</b>To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers.</p><p><b>METHODS</b>A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420).</p><p><b>RESULTS</b>SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the recessive model, individuals with GG genotype at rs1801394 and CC genotype at rs1801133 had a relatively low risk of developing birth defects, so the two genotypes were protective factors against birth defects. The homozygous recessive genotype at rs1801133, which served as a protective factor, was associated with ectoderm- or endoderm-derived complex congenital abnormalities, while the homozygous recessive genotype at rs1801394, which served as a protective factor, was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital abnormalities.</p><p><b>CONCLUSIONS</b>Among the Chinese population in Shanxi Province, the SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex congenital abnormalities and related to ectoderm, mesoderm or endoderm development.</p>
الموضوعات
Humans , Asian People , Genetics , China , Congenital Abnormalities , Genetics , Ferredoxin-NADP Reductase , Genetics , Genotype , Germ Layers , Embryology , Methylenetetrahydrofolate Reductase (NADPH2) , Genetics , Polymorphism, Single Nucleotideالملخص
Embryonic stem (ES) cells have potential for use in evaluation of developmental toxicity because they are generated in large numbers and differentiate into three germ layers following formation of embryoid bodies (EBs). In earlier study, embryonic stem cell test (EST) was established for assessment of the embryotoxic potential of compounds. Using EBs indicating the onset of differentiation of mouse ES cells, many toxicologists have refined the developmental toxicity of a variety of compounds. However, due to some limitation of the EST method resulting from species-specific differences between humans and mouse, it is an incomplete approach. In this regard, we examined the effects of several developmental toxic chemicals on formation of EBs using human ES cells. Although human ES cells are fastidious in culture and differentiation, we concluded that the relevancy of our experimental method is more accurate than that of EST using mouse ES cells. These types of studies could extend our understanding of how human ES cells could be used for monitoring developmental toxicity and its relevance in relation to its differentiation progress. In addition, this concept will be used as a model system for screening for developmental toxicity of various chemicals. This article might update new information about the usage of embryonic stem cells in the context of their possible ability in the toxicological fields.
الموضوعات
Animals , Humans , Mice , Embryoid Bodies , Embryonic Stem Cells , Germ Layers , Mass Screeningالملخص
Although pathology reports of thyroid tissue in ovarian teratomas are abundant, benign teratomas of the thyroid are extremely rare in adolescents and adults. Therefore, their clinical characteristics are still not well characterized. We report a case of a 54-year-old woman with a growing mass in her neck. Left lobectomy of the thyroid revealed it to be a benign thyroid teratoma composed of tissues from all three germ layers. Preoperative evaluations included thyroid ultrasonography (US), ultrasound-guided fine needle aspiration cytology (FNAC), and computed tomography (CT) of the neck. A 4.7-cm, well defined, predominantly hypoechoic mass intermingled with hyperechoic internal lesions, was observed in the inferior portion of the left thyroid lobe with substernal extension on US. The posterior extent of the nodule was not visualized due to deep attenuation of the echo. US-guided FNAC failed to reveal any thyroid follicular cells, but suggested a benign cystic tumor. Neck CT hinted at the diagnosis of teratoma because the mass contained large amounts of fat, and the margin was well defined. Extrathyroidal extension and cervical lymphadenopathy were not seen. She underwent left thyroid lobectomy, and histologic examination confirmed benign thyroid teratoma. To the best of our knowledge, this is the first case report of benign thyroid teratoma in Korea.
الموضوعات
Adolescent , Adult , Female , Humans , Biopsy, Fine-Needle , Germ Layers , Korea , Lymphatic Diseases , Neck , Teratoma , Thyroid Glandالملخص
Isolation of induced pluripotent stem cells (iPSCs) from fully differentiated somatic cells has revolutionized existing concepts of cell differentiation and stem cells. Importantly, iPSCs generated from somatic cells of patients can be used to model different types of human diseases. They may also serve as autologous cell sources that can be used in transplantation therapy. In this study, we investigated the neuronal properties of an iPSC line that is derived from human neonatal foreskin fibroblasts (FS-1). We initially examined the morphology and marker expression of FS-1 cells at undifferentiated stage. We then spontaneously differentiated FS-1 cells in suspension culture and examined the expression of markers representing three germ layers. We finally differentiated FS-1 cells into neuronal lineages by co-culturing them with PA6 stromal cells, and found that, under the conditions we used, they have a tendency to differentiate into more forebrain-type neurons, suggesting that FS-1 iPSC-derived neural cells will be useful to be used in cell therapy of stroke or Huntington's disease, among others. Taken together, FS-1 cells derived from human neonatal fibroblasts exhibit very similar properties with human ES cells, and can provide useful sources for cell therapy and various other applications.
الموضوعات
Humans , Infant, Newborn , Cell Differentiation , Fibroblasts , Foreskin , Germ Layers , Huntington Disease , Induced Pluripotent Stem Cells , Neurons , Pluripotent Stem Cells , Stem Cells , Stroke , Stromal Cells , Cell- and Tissue-Based Therapy , Transplantsالملخص
Mature cystic teratomas of the fallopian tube are unusual, being almost incidentally identified. Here we describe a case of mature cystic teratoma arising in the fallopian tube, in a 44-year-old female. The mass was found during a regular checkup without complication. Microscopically, components from each germ layer were identified.
الموضوعات
Adult , Female , Humans , Fallopian Tubes , Germ Layers , Teratomaالملخص
A teratoma is a germ-cell tumor composed of tissue components representing derivatives of three germ layers. A teratoma in the region of adrenal gland is a rare retroperitoneal tumor. We now report a case of a primary adrenal teratoma. A 38-year-old woman presented with an incidentally detected adrenal mass. The computed tomography scan revealed a 9x8x7.5 cm fat density mass with calcification in the left adrenal gland. The surgically resected tumor was round and well circumscribed and the adrenal gland was present at the periphery of the tumor. The cut surface contained fat tissue and a hair containing cyst. Microscopically, the tumor consisted of adipose tissue, hair, skin appendage, nerve, muscle bundle and bone.
الموضوعات
Adult , Female , Humans , Adipose Tissue , Adrenal Glands , Germ Layers , Hair , Muscles , Retroperitoneal Space , Skin , Teratomaالملخص
A teratoma is a germ-cell tumor composed of tissue components representing derivatives of three germ layers. A teratoma in the region of adrenal gland is a rare retroperitoneal tumor. We now report a case of a primary adrenal teratoma. A 38-year-old woman presented with an incidentally detected adrenal mass. The computed tomography scan revealed a 9x8x7.5 cm fat density mass with calcification in the left adrenal gland. The surgically resected tumor was round and well circumscribed and the adrenal gland was present at the periphery of the tumor. The cut surface contained fat tissue and a hair containing cyst. Microscopically, the tumor consisted of adipose tissue, hair, skin appendage, nerve, muscle bundle and bone.
الموضوعات
Adult , Female , Humans , Adipose Tissue , Adrenal Glands , Germ Layers , Hair , Muscles , Retroperitoneal Space , Skin , Teratomaالملخص
Teratoma is a congenital tumor containing tissues derived from all germ layers. Teratoma in the region of the adrenal gland is a very uncommon retroperitoneal tumor. Only 7 cases of adrenal teratoma have been reported worldwide, but in Korea, no similar cases have been reported until now. This case report describes an adrenal teratoma in a 38-year-old healthy woman who was incidentally diagnosed with a left adrenal mass on abdominal ultrasonography during a medical inspection. Computed tomographic scans revealed a 9-cm heterogeneous circumscribed round mass, containing primarily fat tissue, and a solid calcification component in the left adrenal gland. Adrenal hormonal assessment results and biochemical markers for gonadal neoplasia were negative. Result of serum laboratory tests were normal. The patient underwent laparoscopic adrenalectomy. Histologic analysis confirmed the diagnosis of a mature teratoma; the obtained specimen measured 5 x 7 x 7.5 cm and weighed 267 g. The surface of the mass was smooth, and sebaceous tissue and hair with hard material were observed on the incisional surface. The patient was discharged on postoperative day 4, without complications. In this case report, we describe the incidental finding of a teratoma occurring in the adrenal gland region in a healthy woman; the teratoma was laparoscopically excised.
الموضوعات
Adult , Female , Humans , Adrenal Glands , Adrenalectomy , Germ Layers , Gonads , Hair , Incidental Findings , Korea , Teratoma , Biomarkersالملخص
Embryonic stem cells (ESCs) are an emerging source for cell-based therapies aimed at repairing damaged organ tissues; however, the efficiency of directed differentiation is low and refinement of differentiation protocols is hampered by incomplete understanding of the mechanisms involved in this process. To find new compounds which can improve the efficiency of directed differentiation of ESCs to cardiomyocytes, we screened several thousand chemical compounds and identified a promising group. All of the compounds found have a common structure of 1H-pyrrole,2,2'-(phenylmethylene)bis. Here we report the potential mechanism of action for 31002 which showed the strongest activity among the compounds selected. In the presence of 31002, 15 times more cardiomyocytes differentiated from ESCs, i.e., 3.5% to 52% of total differentiated cells. Moreover, the cardiomyocytes showed functional characteristics including rhythmic beating and marker gene expression. 31002 inhibited the down-regulation of genes related to the three germ layers in the late stage of ESCs differentiation, implying that 31002 supports a continuous fate commitment of undifferentiated ESCs to the cardiac lineage by prolonging the three germ layer stages. Therefore, compounds in this group, including 31002, might be useful as directed cardiomyogenic differentiation-inducers to produce cells for use in cell therapy aimed at restoring damaged heart tissue.
الموضوعات
Down-Regulation , Embryonic Stem Cells , Gene Expression , Germ Layers , Heart , Myocytes, Cardiac , Cell- and Tissue-Based Therapyالملخص
Strong proliferative capacity and the ability to differentiate into the derivative cell types of three embryonic germ layers are the two important characteristics of embryonic stem cells. To study whether the mesenchymal stem cells from human fetal bone marrow (hfBM-MSCs) possess these embryonic stem cell-like biological characteristics, hfBM-MSCs were isolated from bone barrows and further purified according to the different adherence of different kinds of cells to the wall of culture flask. The cell cycle of hfBM-MSCs and MSC-specific surface markers such as CD29, CD44, etc were identified using flow cytometry. The expressions of human telomerase reverse transcriptase (hTERT), the embryonic stem cell-specific antigens, such as Oct4 and SSEA-4 were detected with immunocytochemistry at the protein level and were also tested by RT-PCR at the mRNA level. Then, hfBM-MSCs were induced to differentiate toward neuron cells, adipose cells, and islet B cells under certain conditions. It was found that 92.3% passage-4 hfBM-MSCs and 96.1% passage-5 hfBM-MSCs were at G(0)/G(1) phase respectively. hfBM-MSCs expressed CD44, CD106 and adhesion molecule CD29, but not antigens of hematopoietic cells CD34 and CD45, and almost not antigens related to graft-versus-host disease (GVHD), such as HLA-DR, CD40 and CD80. hfBM-MSCs expressed the embryonic stem cell-specific antigens such as Oct4, SSEA-4, and also hTERT. Exposure of these cells to various inductive agents resulted in morphological changes towards neuron-like cells, adipose-like cells, and islet B-like cells and they were tested to be positive for related characteristic markers. These results suggest that there are plenty of MSCs in human fetal bone marrow, and hfBM-MSCs possess the embryonic stem cell-like biological characteristics, moreover, they have a lower immunogenic nature. Thus, hfBM-MSCs provide an ideal source for tissue engineering and cellular therapeutics.
الموضوعات
Humans , Bone Marrow Cells , Cell Biology , Cell Proliferation , Embryonic Stem Cells , Cell Biology , Fetus , Germ Layers , Cell Biology , Mesenchymal Stem Cells , Cell Biologyالملخص
Los Teratomas son tumores que están compuestos de tejidos derivados de las tres capas germinales. La localización más común en los niños son las sacrococcígeas (40 por ciento), mientras que los ubicados en cabeza y cuello, solo representan el 3,5 por ciento. Desde el punto de vista clínico, los pacientes consultan por la presencia de una masa en el cuello. Los estudios incluyen radiografía simple, ultrasonido, scan de la glándula tiroides, medición de AFP y ß-HCG. La extirpación quirúrgica es el tratamiento de elección. El presente caso clínico trata de un lactante mayor masculino de 12 meses de edad, quien presenta desde el nacimiento, aumento de volumen en la cara antero-lateral izquierda del cuello. Se solicita ecograma cervical reportando: Tumoración ecomixta latero cervical izquierda y ganmagrama tiroideo evidenciándose: bocio multinodular. A los 7 meses de edad se aprecia un aumento mayor de la tumoración y se indica nuevo ecograma: Lóbulo tiroideo izquierdo de tamaño aumentado, con gran imagen nodular, ecomixta. Por lo que se indica Cintilograma tiroideo con I131: Glándula deformada, con una zona hipocaptante que se relaciona con nódulo tiroideo. Se realiza Tiroidectomía ezquierda total con istmectomía. Encontrando hallazgos compatibles con TERATOMA QUÍSTICO MADURO. Los Teratomas de tiroides son tumores muy raros. La mayor incidencia se aprecia en recién nacidos hasta los 2 años de edad. Los pacientes con diagnóstico de malignidad, son tratados con quimioterapia, radioterapia o ambos. Actualmente el niño tiene 10 meses de haber sido intervenido y se encuentra clínicamente estable y sin recidivas.
الموضوعات
Humans , Male , Infant , Goiter/diagnosis , Thyroid Diseases/etiology , Germ Layers/anatomy & histology , Thyroid Neoplasms/surgery , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Histological Techniques/methods , Thyroidectomy/methods , Ultrasonography , Biopsy, Fine-Needle/methods , Hypothyroidism/therapy , Incidence , Pediatrics , Teratoma/surgery , Teratoma/pathologyالملخص
Intracranial teratomas are diagnosed mostly in young population and usually involve midline structure. We report a case of mature teratoma in an adult patient with unusual location in cerebellar hemisphere. A 47-year-old woman presented with severe headache and nausea. Computed tomography and magnetic resonance imaging demonstrated a posterior fossa lesion with cerebellar hemispheric location not involving midline. Histological examination of surgical specimen showed fully matured representative tissues of the three germ layers confirming teratoma. This is a rare example of mature teratoma with unusual age of the patient and location.