It is now well-accepted that obesity-induced inflammation plays an important role in the development of insulin resistance and type 2 diabetes. A key source of the inflammation is the murine epididymal and human visceral adipose tissue. The current paradigm is that obesity activates multiple proinflammatory immune cell types in adipose tissue, including adipose-tissue macrophages (ATMs), T Helper 1 (Th1) T cells, and natural killer (NK) cells, while concomitantly suppressing anti-inflammatory immune cells such as T Helper 2 (Th2) T cells and regulatory T cells (Tregs). A key feature of the current paradigm is that obesity induces the anti-inflammatory M2 ATMs in lean adipose tissue to polarize into proinflammatory M1 ATMs. However, recent single-cell transcriptomics studies suggest that the story is much more complex. Here we describe the single-cell genomics technologies that have been developed recently and the emerging results from studies using these technologies. While further studies are needed, it is clear that ATMs are highly heterogeneous. Moreover, while a variety of ATM clusters with quite distinct features have been found to be expanded by obesity, none truly resemble classical M1 ATMs. It is likely that single-cell transcriptomics technology will further revolutionize the field, thereby promoting our understanding of ATMs, adipose-tissue inflammation, and insulin resistance and accelerating the development of therapies for type 2 diabetes.
Purpose: Skin and soft tissue defect is one of the major challenges faced by plastic surgeons. Adipose derived stromal cells, which can be harvested in large quantities with low morbidity, display multilineage mesodermal potential. Therefore, adipose derived stromal cells have been met with a great deal of excitement by the field of tissue engineering. Recently, Adipose derived stromal cells have been isolated and cultured to use soft tissue restoration. In order to apply cultured cells for clinical purpose, however, FDA approved facilities and techniques are required, which may be difficult for a clinician who cultures cells in a laboratory dedicated to research to utilize this treatment for patients. In addition, long culture period is needed. Fortunately, adipose derived stromal cells are easy to obtain in large quantities without cell culture. The purpose of this study is to present a possibility of using uncultured adipose derived stromal cells for wound coverage. Methods: Seven patients who needed skin and soft tissue restoration were included. Five patients had diabetic foot ulcers, 1 patient got thumb amputation, and 1 patient had tissue defect caused by resection of squamous cell carcinoma. The patients' abdominal adipose tissues were obtained by liposuction. The samples were digested with type I collagenase and centrifuged to obtain adipose derived stromal cells. The isolated adipose derived stromal cells were applied over the wounds immediately after the wound debridement. Fibrin was used as adipose derived stromal cells carrier. Occlusive dressing was applied with films and foams and the wounds were kept moist until complete healing. Results: One hundred to one hundred sixty thousand adipose derived stromal cells were isolated per ml aspirated adipose tissue. All patients' wounds were successfully covered with the grafted adipose derived stromal cells in a 17 to 27 day period. No adverse events related to this treatment occurred. Conclusion: The use of uncultured adipose derived stromal cells was found to be safe and effective treatment for wound coverage without donor site morbidity.
The author has observed the distribution of the tissue mast cells in 67 various tumors and precancerous lesions which occurred in the oral cavity.
The specimcns ware obtained from the department of oral pathology, college of dentistry, Seoul National University, from Jan. 1970 to June, 1973.
The results are as follows:
1) The number of the tissue mast cell was decrease predominantly in malignant tumors, especially in squamous cell carcinomas and in sarcomas.
2) The number of the tissue mast cell distirbution in adenocarcinomas one of malignant group was sligtly increased in with healthy oral mucosa.
3) The number of tissue mast cells in ameloblastomas one of benign group of the tumor of epithelial originwas more decreased than that in healthy oral mucosa.
4) The number of tissue mast cells in fibromas was more than that in healthy oral mucosa.
5) The number of the tissue mast cells in mixed tumors was increased one and a half times as many as that in healthy oral mucosa.
6) The number of the tissue mast cells in mixed tumors was increased one and a half times as many as that in healthy oral mucosa.
7) The tissue mast cell distribution can be observed more densly in the stroma of tumors than in the parenchyme of tumors.
In-Ho Seo;Seung-Jun Lee;Tae Wook Noh;Jung-Hwan Kim;Hyun-Chel Joo;Eui-Cheol Shin;Su-Hyung Park;Young-Guk Ko
IMMUNE NETWORK
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제21권2호
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pp.17.1-17.10
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2021
Abdominal aortic aneurysm (AAA) is a chronic dilation of the aorta with a tendency to enlarge and eventually rupture, which constitutes a major cause of cardiovascular mortality. Although T-cell infiltrates have been observed in AAA, the cellular, phenotypic, and functional characteristics of these tissue-infiltrating T cells are not fully understood. Here, we investigated the proportional changes of T-cell subsets-including CD4+ T cells, CD8+ T cells, and γδ T cells-and their effector functions in AAAs. We found that Vδ2+ T cells were presented at a higher frequency in aortic aneurysmal tissue compared to normal aortic tissue and PBMCs from patients with AAA. In contrast, no differences were observed in the frequencies of CD4+, CD8+, and Vδ1+ T cells. Moreover, we observed that the Vδ2+ T cells from AAA tissue displayed immunophenotypes indicative of CCR5+ non-exhausted effector memory cells, with a decreased proportion of CD16+ cells. Finally, we found that these Vδ2+ T cells were the main source of IL-17A in abdominal aortic aneurysmal tissue. In conclusion, our results suggest that increased Vδ2+ T cells that robustly produce IL-17A in aortic aneurysmal tissue may contribute to AAA pathogenesis and progression.
Pleomorphic adenoma is the most common benign tumor in salivary glands, and occurred in frequency of 60% in parotid gland tumors, and 50% in submandibular gland tumors, and 25% in sublingual gland tumors. Histopathologically, pleomorphic adenoma is composed of epithelial cells and mesenchymal tissues, and called 'mixed tumor' because of morphological divergency. The cell structures of luminal area are composed of polyhedral and cuboidal secretory epithelial cells and modified myoepithelial cells around it, and mesenchymal tissue is composed of some myoepithelial cells and stromal tissue. In stromal tissue, myxoid change, chondroid change, or hyalinization can be seen even if bone tissue. In many studies, tumor cells of pleomorphic adenoma containing modified myoepithelial cell participate in synthesis of glycosaminoglycans. In this study, tissue sample of pleomorphic adenoma of human salivary gland were obtained from 20 surgical specimens, and all specimens were routinely fixed in 10% formalin and embedded. Serial 4-8${\mu}m$ thick sections were cut from paraffin blocks. The histopathologic evaluation was done with light microscopy. And, with immunohistochemical staining, characteristics of glycosaminoglycan were observed. And, for biochemical analysis of glycosaminoglycan, isolation of crude glycosaminoglycan from tumor tissue and immuno-blot analysis were carried out. With transmission electromicroscopy, tumor cells and biologic behavior of pleomorphic adenoma were observed with distribution and expression of glycosaminoglycan in tumor cells, The results were obtained as follows: 1. In immunohistochemical study, chondroitin 4-sulfate is highly postively stained in myxoid stromal tissue, and chondroitin 6-sulfate is highly positively stained in chondroid mesenchymal tissue, both glycosaminoglycans are positively stained in non-luminal cell of ductal area. 2. Dermatan sulfate and keratan sulfate is positively stained in periductal non-luminal tumor cells. 3. In immunohistochemical study, heparan sulfate is weakly stained in luminal cells and non-luminal cells around duct, and chondroid mesenchymal tissue. 4. In transmission electromicroscopic view, the tumor cells are composed of modified myoepithelial cells, and contain many microfilaments and well developed rough endoplasmic reticulum. 5. In Immuno-Blot analysis, the expression of glycosaminoglycans is expressed mostly in chondroitin 6-sulfate and chondroitin 4-sulfate. From the results obtained in this study, tumor cells of pleomorphic adenoma are composed of modified myoepithelial cells, and glycosaminoglycans of chondroitin 4-sulfate and chondroitin 6-sulfate mostly participate in the development of pleomorphic adenoma, but dermatan sulfate, keratan sulfate and heparan sulfate glycosaminoglycans were expressed variably.
Tissue engineering and regenerative medicine strategies could offer new hope for patients with serious tissue injuries or end-stage organ failure. Scientists are now applying the principles of cell transplantation, material science, and engineering to create biological substitutes that can restore and maintain normal function in diseased or injured tissues/organs. Specifically, creation of engineered tissue construct requires a polymeric biomaterial scaffold that serves as a cell carrier, which would provide structural support until native tissue forms in vivo. Even though the requirements for scaffolds may be different depending on the target applications, a general function of scaffolds that need to be fulfilled is biodegradability, biological and mechanical properties, and temporal structural integrity. The scaffold's internal architecture should also enhance the permeability of nutrients and neovascularization. In addition, the stem cell field is advancing, and new discoveries in tissue engineering and regenerative medicine will lead to new therapeutic strategies. Although use of stem cells is still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous adult cells have already entered the clinic. This review discusses these tissue engineering and regenerative medicine strategies for various tissues and organs.
The cancer stem cell (CSC) hypothesis has captured the attention of many scientists. It is believed that elimination of CSCs could possibly eradicate the whole cancer. CSC surface markers provide molecular targeted therapies for various cancers, using therapeutic antibodies specific for the CSC surface markers. Various CSC surface markers have been identified and published. Interestingly, most of the markers used to identify CSCs are derived from surface markers present on human embryonic stem cells (hESCs) or adult stem cells. In this review, we classify the currently known 40 CSC surface markers into 3 different categories, in terms of their expression in hESCs, adult stem cells, and normal tissue cells. Approximately 73% of current CSC surface markers appear to be present on embryonic or adult stem cells, and they are rarely expressed on normal tissue cells. The remaining CSC surface markers are considerably expressed even in normal tissue cells, and some of them have been extensively validated as CSC surface markers by various research groups. We discuss the significance of the categorized CSC surface markers, and provide insight into why surface markers on hESCs are an attractive source to find novel surface markers on CSCs.
Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thus represent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeutic strategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectively inhibited human AML $CD34^+CD38^-$ cell proliferation in vitro culture in a dose-dependent manner while sparing normal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASP exerted cytotoxic effects on AML K562 cells, especially LSC-enriched $CD34^+CD38^-$ cells. Colony formation assays further showed that ASP significantly suppressed the formation of colonies derived from AML $CD34^+CD38^-$ cells but not those from normal $CD34^+CD38^-$ cells. Examination of the underlying mechanisms revealed that ASP induced $CD34^+CD38^-$ cell senescence, which was strongly associated with a series of characteristic events, including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16, P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of these findings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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제28권1호
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pp.42-45
/
2002
Cultures of primary human alveolar bone-derived cells were established from alveolar bone chips obtained from normal individuals undergoing tooth extraction. These cells were expanded in vitro until passage 3 and used for the in vivo assays. Cells were loaded into transplantation vehicles, and transplanted subcutaneously into immunodeficient mice to study the capacities of human alveolar bone-derived cells to form bone in vivo. Transplants were harvested 12 weeks after transplantation and evaluated histologically. Of 10 human alveolar bone-derived cell transplants, two formed a bone-like tissue that featured osteocytes and mineral. Eight of the ten formed no osseous tissue. These results show that cells from normal human alveolar bone are capable of forming bone-like tissue when transplanted into immunodeficient mice.
Purpose: Adipose tissue is located beneath the skin, around internal organs, and in the bone marrow in humans. Its main role is to store energy in the form of fat, although it also cushions and insulates the body. Adipose tissue also has the ability to dynamically expand and shrink throughout the life of an adult. Recently, it has been shown that adipose tissue contains a population of adult multipotent mesenchymal stem cells and endothelial progenitor cells that, in cell culture conditions, have extensive proliferative capacity and are able to differentiate into several lineages, including, osteogenic, chondrogenic, endothelial cells, and myogenic lineages. Materials and Methods: This study focused on endothelial cell culture from the adipose tissue. Adipose tissues were harvested from buccal fat pad during bilateral sagittal split ramus osteotomy for surgical correction of mandibular prognathism. The tissues were treated with 0.075% type I collagenase. The samples were neutralized with DMEM/and centrifuged for 10 min at 2,400 rpm. The pellet was treated with 3 volume of RBC lysis buffer and filtered through a 100 ${\mu}m$ nylon cell strainer. The filtered cells were centrifuged for 10 min at 2,400 rpm. The cells were further cultured in the endothelial cell culture medium (EGM-2, Cambrex, Walkersville, Md., USA) supplemented with 10% fetal bovine serum, human EGF, human VEGF, human insulin-like growth factor-1, human FGF-$\beta$, heparin, ascorbic acid and hydrocortisone at a density of $1{\times}10^5$ cells/well in a 24-well plate. Low positivity of endothelial cell markers, such as CD31 and CD146, was observed during early passage of cells. Results: Increase of CD146 positivity was observed in passage 5 to 7 adipose tissue-derived cells. However, CD44, representative mesenchymal stem cell marker, was also strongly expressed. CD146 sorted adipose tissue-derived cells was cultured using immuno-magnetic beads. Magnetic labeling with 100 ${\mu}l$ microbeads per 108 cells was performed for 30 minutes at $4^{\circ}C$ a using CD146 direct cell isolation kit. Magnetic separation was carried out and a separator under a biological hood. Aliquous of CD146+ sorted cells were evaluated for purity by flow cytometry. Sorted cells were 96.04% positivity for CD146. And then tube formation was examined. These CD146 sorted adipose tissue-derived cells formed tube-like structures on Matrigel. Conclusion: These results suggest that adipose tissue-derived cells are endothelial cells. With the fabrication of the vascularized scaffold construct, novel approaches could be developed to enhance the engineered scaffold by the addition of adipose tissue-derived endothelial cells and periosteal-derived osteoblastic cells to promote bone growth.
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