骨组织工程中的间质干细胞：成骨活性、免疫特性、促血管化及成骨效应

BACKGROUND: It is still a challenge to repair bone defects caused by trauma, infection, tumor and congenital diseases. Bone tissue engineering is a promising method for bone defect repair showing important guiding significance in the clinic. OBJECTIVE: To review the progress of proliferation, osteogenic activity, immunogenicity, proangiogensis and in vivo osteogenic effect of mesenchymal stem cells in bone tissue engineering. METHODS: The first author retrieved Wanfang and PubMed datebase for literatures published from 2008 to 2016, using the keywords of “mesenchymal stem cell, tissue engineering, osteogenesis, immune property, angiogenesis” in Chinese and English, respectively. Articles regarding mesenchymal stem cells, tissue engineering, osteogenesis, immune property and angiogenesis were included, and repetitive and dated studies were excluded. Totally 1 772 articles were retrieved initially, and in accordance with inclusion and exclusion criteria, 41 eligible articles were included for review analysis. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells and adipose-derived mesenchymal stem cells are extensively applied in bone tissue engineering. Studies have shown that the osteogenic activity of bone marrow mesenchymal stem cells is higher than that of adipose-derived mesenchymal stem cells, but its immune regulation effect is weaker than that of adipose-derived mesenchymal stem cells. Mesenchymal stem cells hold remarkable immune regulation (immunosuppression and immune enhancement) and tissue repair capacity, which can eliminate inflammatory reactions at injured sites, promoting tissue repair. Adipose-derived mesenchymal stem cells cultured under hypoxia environment can secret more angiogenic cytokines generating more vascular structures. Furthermore, increasing proof have confirmed that porous nano-polylactic acid combined with nano-carbon biological material can significantly promote the proliferation and osteogenesis of bone marrow mesenchymal stem cells. Taking its tumorigenesis into consideration, mesenchymal stem cells should be prudently used in the clinic. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Mechanism and application of stem cell-derived exosomes in promoting diabetic wound healing北大核心

BACKGROUND: The exosomes are one of important active components of adult stem cells paracrine, providing the basis for stem cell “non-cellular” treatment. Exosomes from stem cells can play different roles in the wound through different mechanisms to promote the healing of diabetic wounds. OBJECTIVE: To summarize the main mechanism and application of stem cell derived exosomes in the treatment of diabetic wounds. METHODS: Computers were used to retrieve English databases such as PubMed database, Web of Science database, FMRS foreign language medical information resource retrieval platform, and Chinese databases such as CNKI and Wanfang Data Knowledge Service Platform. The retrieval scope was from the inception of the database to September 2020. The English and Chinese search terms were “stem cells, exosomes, wound healing, cell proliferation, neovascularization, inflammation, extracellular matrix, therapeutic use”. According to the inclusion and exclusion criteria, 66 articles were included and the results were analyzed. RESULTS AND CONCLUSION: (1) It is summarized that stem cell-derived exosomes can promote diabetic wound healing by regulating inflammation, promoting neovascularization, re-epithelialization and remodeling of extracellular matrix. (2) The application of stem cell-derived exosomes in diabetic wounds was listed. (3) The exosomes from stem cells can avoid the immune response of stem cells in the treatment of diabetic wounds, and the genetic material of stem cells carried by them is more widely regulated and more effective than that from ordinary cells in the treatment of diabetic wounds. (4) At present, the application of stem cell derived exosomes in diabetes wounds still has some problems, such as low purity, high cost of separation, low production efficiency, and the way to reach the target area, loss rate and diffusion efficiency. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Acquisition and application of ectodermal mesenchymal stem cells北大核心

BACKGROUND: Ectodermal mesenchymal stem cells are a kind of adult stem cells, which are easy to obtain and abundant in source, and play an important role in tissue repair and immune regulation. OBJECTIVE: To summarize the latest progress in the acquisition and application of ectodermal mesenchymal stem cells. METHODS: Web of Science was searched with the key words of “ectodermal mesenchymal stem cells, stem cell therapy, spinal cord injury, neurodegenerative disease, sepsis”. The indexes were original studies and reviews. The retrieval period was from the establishment of the database to 2021. Totally 85 relevant articles were screened out and analyzed and summarized with the document tracing method. RESULTS AND CONCLUSION: (1) Ectodermal mesenchymal stem cells are abundant and easy to obtain, and can be derived from dental tissue, nasal mucosa, and corneal tissue. Similar to mesoderm mesenchymal stem cells, they have the ability of multi-line differentiation and immunomodulatory function. (2) Epidermal mesenchymal stem cells share homology with dental tissue and neural tissue. Ectodermal mesenchymal stem cells have better ability of ligaments and nervous tissue differentiation, so they have unique advantages in dental tissue repair, spinal cord injury repair, neurodegenerative disease treatment and so on, so they have a very broad application prospect. (3) Immunomodulatory function of ectodermal mesenchymal stem cells also cannot be ignored. There is only a small amount of literature reports applied to sepsis and other immune diseases, but studies found that its immune regulation mechanism is same as mesoderm mesenchymal stem cells. In the meanwhile, the acquisition of ectodermal mesenchymal stem cells is less invasive; therefore, ectoderm mesenchymal stem cells have excellent prospects of clinical application. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Important role of glutathione in stemness and regulation of stem cells北大核心

BACKGROUND: Stem cells possess the capacities of self-renewal and multiple differentiation. Glutathione, an important sulfhydryl compounds, not only participates in the active oxygen metabolism of stem cells, but also plays an important role in self-renewal, proliferation, aging, stemness maintenance and differentiation regulation of stem cells. OBJECTIVE: To explore the important role of glutathione in stem cells. METHODS: In April 2020, the first author searched the title/abstract with the English keywords of “glutathione or GSH, stem cell”, and searched any field with the Chinese keywords of “glutathione, stem cell”, and searched the related articles included in CNKI, VIP, Wanfang and PubMed databases from 2000 to 2020. A total of 358 Chinese articles and 405 English articles were retrieved. Finally, 86 eligible articles were enrolled for the analysis after deleting the repetitive and non-conforming articles. RESULTS AND CONCLUSION: By reviewing the recent studies on glutathione and stem cells, we found that glutathione played an important role in maintaining stemness, regulating the differentiation of stem cells. In addition, effects of glutathione on cancer stem cells have been verified, which provides more evidence for the future treatment of cancer with reduced glutathione. Key words:. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Exosomes that deliver specific mirnas can regulate osteogenesis and promote angiogenesis北大核心

BACKGROUND: Exosomes are nanoscale paracrine vesicles containing a variety of bioactive factors, such as miRNAs. Exosome miRNAs play an important role in intercellular communication. In recent years, more and more studies have focused on whether miRNAs in exosomes promote bone regeneration. OBJECTIVE: To review research status of exosomal miRNAs promoting bone regeneration in the recent years so as to provide a theoretical basis for further research and application in the field of bone regeneration. METHODS: Using “bone regeneration, bone repair, exosomes, miRNA” in Chinese and English as search terms, biomedical literature database, CNKI, and PubMed were retrieved for articles on exosomal miRNA and bone regeneration published from 2010 to 2021. RESULTS AND CONCLUSION: Exosomes derived from different cells can effectively regulate osteogenesis and promote angiogenesis through the delivery of specific miRNAs, which has a broad prospect in bone tissue engineering. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Research hotspot of biological scaffold materials promoting osteogenic differentiation of bone marrow mesenchymal stem cells北大核心

BACKGROUND: At present, a single biological scaffold material is difficult to meet the osteogenic needs of bone tissue engineering, and bone marrow mesenchymal stem cells have excellent osteogenic characteristics. Composite scaffolds and scaffolds combined with growth factors have better osteogenic ability. It is a research hotspot at present. OBJECTIVE: To review different biological scaffolds and their modified scaffolds to promote the osteogenic differentiation of bone marrow mesenchymal stem cells. METHODS: The related articles published in CNKI, Wanfang, VIP, PubMed and Embase databases from January 2014 to July 2020 were searched by the first author with the keywords of “bone marrow mesenchymal stem cells, scaffolds, osteogenic differentiation, hydroxyapatite, collagen, chitosan” in English and Chinese. Finally, 69 articles were selected. RESULTS AND CONCLUSION: The rapid development of bone tissue engineering can effectively solve the problem of bone defect repair. Seed cells and biological scaffold materials are the core of bone tissue engineering. Bone marrow mesenchymal stem cells have excellent osteogenic differentiation ability and are widely used in bone tissue engineering. The combination of different scaffold materials, the use of advanced preparation technology, or the surface modification of scaffolds and the addition of growth factors can fully combine the advantages of various biological scaffold materials, induce the osteogenic differentiation of bone marrow mesenchymal stem cells and the formation of scaffold blood vessels, and achieve the purpose of repairing bone defects, and is the research focus of bone tissue engineering. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Immunology of stem cells and cancer stem cells

The capacity of pluri-potent stem cells to repair the tissues in which stem cells reside holds great promise in development of novel cell replacement therapeutics for treating chronic and degenerative diseases. However, numerous reports show that stem cell therapy, even in an autologous setting, triggers lymphocyte infiltration and inflammation. Therefore, an important question to be answered is how the host immune system responds to engrafted autologous stem cells or allogeneous stem cells. In this brief review, we summarize the progress in several related areas in this field, including some of our data, in four sections： （1） immunogenicity of stem cells; （2） strategies to inhibit immune rejection to allograft stem cells; （3） immune responses to cancer stem cells; and （4） mesenchymal stem cells in immune regulation. Improvement of our understanding on these and other aspects of immune system-stem cell interplay would greatly facilitate the development of stem cell-based therapeutics for regenerative purposes. Cellular ＆ Molecular Immunology.     

Inhalation of bone marrow mesenchymal stem cells-derived exosomes alleviates inflammatory injury in chronic obstructive pulmonary disease北大核心

BACKGROUND: Many studies have demonstrated that exosomes derived from bone marrow mesenchymal stem cells show strong repair and regeneration ability in various models of respiratory inflammation and disease injury, but there are few studies on chronic obstructive pulmonary disease, and no studies have applied aerosolized inhalation of exosomes in model experiments of chronic obstructive pulmonary disease. OBJECTIVE: To investigate the therapeutic effects of exosomes derived from rat bone marrow mesenchymal stem cells on inflammation and lung injury in rats with chronic obstructive pulmonary disease by aerosol inhalation, and to determine the optimal therapeutic dose. METHODS: Rat bone marrow mesenchymal stem cells were isolated and cultured in vitro, and exosomes were extracted and identified. The rat model of chronic obstructive pulmonary disease was established by lipopolysaccharide combined with smoking for 28 days. Then low dose (0.5×108 particles/kg), medium dose (1.0×108 particles/kg), and high dose (1.5×108 particles/kg) exosome aerosol treatment and exosome (1.5×108 particles/kg) were given by tail vein injection. The model group was atomized with 1 mL PBS, while the control group was not molded with 1 mL PBS. Continuous atomization or injection was conducted for 5 days, and the test was started on the second day after the last atomization or injection treatment. The lung function indexes were tested by small animal pulmonary function instrument. The levels of interleukin-1β and tumor necrosis factor-α in bronchoalveolar lavage fluid and serum were detected by ELISA. The changes of lung tissues were assessed histologically by hematoxylin-eosin staining and Masson staining. RESULTS AND CONCLUSION: (1) The exosomes of bone marrow mesenchymal stem cells showed elliptic double-membrane vesicles under transmission electron microscopy, which were typical cup-shaped. Particle size analysis indicated that the peak diameter of exosomes was 91.7 nm, accounting for 97.3%, and the particle concentration was 3.3×109 L-1. In addition, surface proteins CD9 and CD63 were highly expressed. (2) Compared with caudal vein injection of exosome, aerosol inhalation of exosome significantly improved lung function, collagen deposition and pathological changes of lung tissue in rats with chronic obstructive pulmonary disease, and significantly decreased the levels of interleukin-1β and tumor necrosis factor-α in bronchoalveolar lavage fluid and serum. The low exosome dose had the most significant therapeutic effect. (3) These results suggest that inhalation of exosomes from bone marrow mesenchymal stem cells can reduce inflammatory injury in chronic obstructive pulmonary disease and the optimal dose may be 0.5×108 particles/kg. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

中药诱导骨髓间充质干细胞的定向分化：研究与进展

BACKGROUND: In recent years, in-depth studies that single Chinese herbs or extracts, compound traditional Chinese medicine and medicated serum are used to regulate the directional differentiation of bone marrow mesenchymal stem cells into myofibroblasts, chondrocytes, osteoblasts, myocardial cells and nerve cells, which have become a highlight in the tissue engineering research.OBJECTIVE: To review the latest progress in the directional differentiation of bone marrow mesenchymal stem cells induced by Chinese herbs or their extracts.METHODS: The first author searched the CNKI, Wanfang and PubMed databases using the keywords of “Chinese herb, directional differentiation, mesenchymal stem cells” in Chinese and English, respectively, to retrieve relevant articles published from January 2010 to January 2016. Repetitive articles or those with no originality were eliminated. Totally 99 articles were searched initially, and then 43 articles were included in result analysis.RESULTS AND CONCLUSION: As the strongest seed cells in the bone differentiation system, bone marrow mesenchymal stem cells have a wide range of directional differentiation potential, and highlight the important value in combination with Chinese herbs for clinical treatment of various refractory diseases, especially for treatment of metabolic bone diseases, bone defects, nonunion and delayed union, which is not only conducive to in-depth, multi-angle studies on effects and mechanisms of Chinese herbs, but also to clinical treatment of various refractory diseases using bone marrow mesenchymal stem cells.   中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Stem cells combined with three-dimensional scaffolds for the treatment of osteoporotic bone defects北大核心

BACKGROUND: Stem cells combined with a three-dimensional scaffold have great potential for the treatment of osteoporotic bone defects. OBJECTIVE: To introduce the application of stem cells combined with the three-dimensional scaffold in repairing osteoporotic bone defects. METHODS: A computer-based search of PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases was performed for relevant articles published from 2007 to 2017 with “stem cells, scaffold, osteoporosis, bone defects” as key words in English and Chinese, repsectively. Initially, 142 articles were retrieved, and finally 45 articles were included in result analysis. RESULTS AND CONCLUSION: Due to the potential of self-renewal and multilineage differentiation, stem cells can be used to repair or regenerate damaged tissues, which are considered as an ideal cell source for the treatment of diseases in orthopedics. The suitable scaffold can provide a favorable microenvironment for repairing the attachment and growth of the cells related to the bone defect, which can promote the healing without additional side effects. Furthermore, stem cells combined with three-dimensional scaffolds provide a promising clinical application for the treatment of osteoporotic bone defects by regulation of bone metabolism. In addition, gene-modified stem cells with three-dimensional scaffolds bring a huge potential in the treatment of osteoporotic bone defects. In conclusion, the combination of stem cells and three-dimensional scaffolds provides a new approach for the treatment of osteoporotic bone defects, which may be one of the future therapeutic strategies. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

间充质干细胞对再生障碍性贫血患者造血支持及T淋巴细胞分泌功能的影响

BACKGROUND: Recently, the role of mesenchymal stem cells in aplastic anemia has been widely explored. However, its underlying mechanism remains unclearly.OBJECTIVE:To study the effect of umbilical cord blood and bone marrow mesenchymal stem cells on hematopoietic support and secretory function of T lymphocytes in patients with aplastic anemia.METHODS:Cord blood and bone marrow samples from 48 cases of aplastic anemia and 48 healthy lying-in women to isolate mesenchymal stem cells using flow cytometry. Mesenchymal stem cells from the cord blood and bone marrow were respectively co-cultured with cord blood mononuclear cells to count burst forming units-erythroid and colony forming units-granulocyte/macrophage. Mesenchymal stem cells were co-cultured with T lymphocytes from aplastic anemia patients undergoing phytohemagglutinin stimulation, and ELISA was used to detect interleukin-2, interleukin-4 and interferon-γ levels secreted from T lymphocytes.RESULTS AND CONCLUSION: The number of burst forming units-erythroid and colony forming units-granulocyte/macrophage significantly increased in normal bone marrow or umbilical cord blood mesenchymal stem cells co-cultured with cord blood mononuclear cells (P < 0.05), but reduced remarkably in umbilical cord blood mesenchymal stem cells from aplastic anemia patients co-cultured with cord blood mononuclear cells (P < 0.05). Levels of interleukin-2, interleukin-4 and interferon-γ from T lymphocytes were inhibited significantly after co-culture with normal bone marrow mesenchymal stem cells compared with phytohemagglutinin-induced T lymphocytes (P < 0.05). There was a similar inhibitory effect after co-culture with normal umbilical cord blood mesenchymal stem cells. There was a significantly reduction in the capacity of inhibiting interleukin-2, interleukin-4 and interferon-γ levels from T lymphocytes after co-culture with bone marrow mesenchymal stem cells from aplastic anemia patients (P < 0.05). Aplastic anemia patients show some functional defects in their bone marrow mesenchymal stem cells that have a weaker inhibitory role than normal bone marrow or umbilical cord blood mesenchymal stem cells in the hematopoietic support and secretory function of T lymphocytes. These findings indicate that mesenchymal stem cells from aplastic anemia patients can influence the pathological progress through weakening hematopoietic support and secretory function of T lymphocytes.  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Dendritic cells as a pharmacological target of traditional Chinese medicine

Dendritic cells （DCs） represent a heterogeneous population of professional antigen-presenting cells （APCs） that play a central role in the initiation and regulation of immune responses. There is considerable evidence that DCs can be used as therapeutic targets for pharmacological modulation of immune responses. Traditional Chinese medicine （TCM） has a long-standing history of using herbal medicine in the treatment of variety of human diseases. Many of the clinical effects of TCM have reportedly been attributed to the up- or down-regulation of immune responses. Accumulating evidence indicates that TCM and its components can interfere with immune responses at the earliest stage by targeting key functions of DCs. Here, we review those published studies of TCM with respect to their effects on immunobiological functions of DCs. Investigations based on both chemical entities derived from TCM as well as TCM herbal mixtures are presented. These studies suggest that various TCM herbal medicines have the capacity to inhibit or promote major functions of DCs, such as differentiation, maturation, cytokine production, survival, antigen uptake and presentation as well as trafficking. These studies have revealed novel biological effects of TCM and documented the utility of this approach to discover novel biological modifier of DC functions derived from natural sources.     

Adipose tissue engineering construction using adipose-derived stem cells and scaffolds in breast reconstruction北大核心

BACKGROUND: The development of adipose tissue engineering has solved a series of problems and brought new ideas for breast reconstruction. OBJECTIVE: To summarize the main biological characteristics of scaffolds, seed cells and adipose grafts for adipose tissue engineering construction, as well as their application prospects in breast reconstruction. METHODS: With the key words of “scaffold, mesenchymal stem cells, adipose tissue engineering, breast reconstruction, vascularization” in Chinese and English, respectively, a retrieval of CNKI and PubMed was performed for relevant articles published from 1999 to 2017. After initial screening, the eligible articles were further detailed, analyzed and summarized. RESULTS AND CONCLUSION: Scaffold materials with low immunogenicity, especially the decellularized adipose tissue, have a unique advantage in adipogenic induction that can be used to support the regeneration of human organs and tissues. Adipose-derived stem cells can also be used as the priority for adipose tissue engineering construction, which can promote tissue development and regeneration in vivo. However, much less is known about the use of adipose tissue engineering in breast reconstruction and the implementation of long-term stable growth of the adipose tissues. Further investigations are indispensable on how to realize breast reconstruction using tissue-engineered adipose so as to construct and maintain a stable structure entity throughout the entire patient’s life. Therefore, strict selection of seed cells, scaffolds and cytokines is considered pivotal in the construction of cell microenvironment. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

骨髓间充质干细胞移植后在胸腺内的定居

BACKGROUND: Bone marrow mesenchymal stem cells have low immunogenicity and can induce immune tolerance. At present, the mechanism of immune regulation of bone marrow mesenchymal stem cells is not completely understood. It has been rarely reported whether the bone marrow mesenchymal stem cells can migrate to the thymus after transplantation.OBJECTIVE: To observe the distribution and survival of bone marrow mesenchymal stem cells in the thymus of aging rats after transplantation.METHODS:Bone marrow mesenchymal stem cells cultured in vitro were transfected by adenovirus vectors expressing green fluorescent protein. Transfected bone marrow mesenchymal stem cells were injected into the portal vein of aging rats. At days 3, 7, 14, 21 after transplantation, the survival of bone marrow mesenchymal stem cells homing to the thymus was observed under fluorescence microscope. At day 3 after transplantation, thymus tissues were taken and stained with hematoxylin-eosin for pathological observation. RESULTS AND CONCLUSION:Green fluorescent protein-labeled bone marrow mesenchymal stem cells had a strong green fluorescence at days 3 and 7 after transplantation, and the cell contour was clear. There was no significant difference in the mean absorbance values at days 3 and 7 (P > 0.05). Expression of green fluorescent protein was weakened significantly at days 14 and 21 compared with that at day 3 (P < 0.05). At 3 days after transplantation, the transplanted bone marrow mesenchymal stem cells were clearly visible in the thymus, and acute rejection was not observed. The results show that bone marrow mesenchymal stem cells can migrate to the damaged thymus tissue through the blood circulation, and can survive at least 1 week.  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

细胞因子对骨骼肌细胞和胰岛β细胞的作用

BACKGROUND: A variety of cytokines such as cytokines, growth factors and inflammatory proteins play an important role in the development of skeletal muscle. OBJECTIVE:To investigate the biological characteristics of a variety of cytokines and their effects on skeletal muscle cells and pancreatic β cells. METHODS: Relevant articles published from 2002 to 2015 were retrieved in CNKI and PubMed databases using the English keywords “cytokines, adiponectin, leptin, visfatin, skeletal muscle cells, pancreatic β cells”. Initially 253 literatures were obtained, and finally 53 eligible literatures were included based on the exclusion criteria. RESULTS AND CONCLUSION: As a fat-specific protein newly found, adiponectin can improve the insulin sensitivity by promoting glucose uptake, storage and utilization in skeletal muscle cells. The activation of muscle satellite cells and skeletal myoblast proliferation are both dependent on leptin, so leptin plays a vital role in the skeletal muscle cell growth and development. Visfatin, a pleiotropic cytokine, widely presents in the skeletal muscle, liver and bone marrow, and participates in the regulation of inflammation and immune function. Furthermore, visfatin contributes to glucose uptake and metabolism in the skeletal muscle, and makes considerable effects on the stress and signal transduction of skeletal muscle cells. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Application and progress of small extracellular vesicles in periodontal and pulp regeneration北大核心

BACKGROUND: Small extracellular vesicles are important components of paracrine pathways. In recent years, the application of small extracellular vesicles in oral tissue regeneration attracted wide attention. OBJECTIVE: To review the role and application of small extracellular vesicles in periodontal and pulp tissue regeneration. METHODS: PubMed, Web of Science, CNKI and Wanfang databases were searched for relevant articles published in the past ten years. The retrieval MeSH Terms or key words were “small extracellular vesicles, exosomes, pulp stem cells, periodontal regeneration, bone regeneration, pulp regeneration, regenerative endodontics, revascularization” in Chinese and English, respectively. After removal of poorly related, outdated, and duplicate studies by reading the title and abstract, 71 articles were finally included in result analysis. RESULTS AND CONCLUSION: (1) Small extracellular vesicles were secreted by many kinds of cells, participated in intercellular communication and mediated immune response. Small extracellular vesicles have a great application potential in tissue regeneration. (2) Small extracellular vesicles play an important role in periodontal tissue repair and regeneration. Small extracellular vesicles can regulate periodontal inflammation and promote periodontal ligament and surrounding bone tissue regeneration. (3) Small extracellular vesicles improve dental stem cells to regenerate functional pulp-dentin complexes. © 2023, Chinese Journal of Tissue Engineering Research. All rights reserved.     

Application of engineered exosomes in bone repair and regeneration北大核心

BACKGROUND: Bone defect caused by disease or accident is very common in clinic. The current main treatment method for bone defect repair is autologous bone grafting. Autologous bone grafting may cause complications, such as secondary infections and scars. The other treatments, such as allogeneic bone transplantation, may have risks of immune rejection and disease transmission. Furthermore, safety considerations and the performance of biomaterials and cell-based treatment require further clarification. In recent years, engineered exosomes have shown good application potential in bone repair and bone regeneration, and have become a current research hotspot. OBJECTIVE: To review the research progress of engineering exosomes in promoting bone defect repair and bone regeneration. METHODS: The PubMed, CNKI and Wanfang databases were searched for relevant articles with the key words of “exosome; engineered exosomes; bone repair; bone regeneration” in English and Chinese, respectively. The search time was from January 1980 to September 2020. Articles that were not related to the purpose of the research and repetitive articles were excluded, and 56 articles that met the criteria were finally included for review. RESULTS AND CONCLUSION: The engineered exosomes can not only promote bone differentiation of osteoblast-related cells and new blood vessel formation, but also target tissues and cells. A large number of experiments have proven that the engineered exosomes for repairing bone defect and promoting bone regeneration is a feasible strategy. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Dental pulp stem cells in tissue engineering: Application and development北大核心

BACKGROUND: As a special source of stem cells, dental pulp stem cells (DPSCs) make much progress in the development of tissue engineering field due to their high proliferation and self-renewal ability. In the certain conditions DPSCs can be induced to differentiate into a variety of specialized tissue cells, providing a new way for tissue engineering development. OBJECTIVE: To review the main progress in the DPSCs biological characteristics, original source, isolation method, and its related application in tissue engineering research. METHODS: “Dental pulp stem cell, differentiation, regenerative medicine, tissue engineering” in English and Chinese were termed as the keywords to search relevant articles about DPSCs and tissue engineering published from 2005 to 2017 in PubMed, Medline, WanFang, and CNKI databases. After removal of repetitive or irrelevant articles, 66 articles were finally reviewed. RESULTS AND CONCLUSION: With the development of tissue engineering and regenerative medicine, the effective combination of DPSCs and tissue engineering scaffolds have be further achieved. Recent studies on DPSCs focus on the properties of DPSCs differentiating into odontoblasts and osteocytes/osteoblasts and on the potential of nerve repair, vascular remodeling, corneal reconstruction and chondrogenic differentiation. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Dendritic Cell-Derived Exosomes Stimulate Stronger CD8~+ CTL Responses and Antitumor Immunity than TVimor Cell-Derived Exosomes

Exosomes (EXO) derived from dendritic cells (DC) and tumor cells have been used to stimulate antitumor immune responses in animal models and in clinical trials. However, there has been no side-by-side comparison of the stimulatory efficiency of the antitumor immune responses induced by these two commonly used EXO vaccines. In this study, we selected to study the phenotype characteristics of EXO derived from a transfected EG7 tumor cells expressing ovalbumin (OVA) and OVA-pulsed DC by flow cytometry. We compared the stimulatory effect in induction of OVA-specific immune responses between these two types of EXO. We found that OVA protein-pulsed DCovA-derived EXO (EXODC) can more efficiently stimulate naive OVA-specific CD8+ T cell proliferation and differentiation into cytotoxic T lymphocytes in vivo, and induce more efficient antitumor immunity than EG7 tumor cell-derived EXO (EXOEG7). In addition, we elucidated the important role of the host DC in EXO vaccines that the stimulatory effect of EXO is delivered to T cell responses by the host DC. Therefore, DC-derived EXO may represent a more effective EXO-based vaccine in induction of antitumor immunity.     

Dendritic Cell-Derived Exosomes Stimulate Stronger CD8^＋ CTL Responses and Antitumor Immunity than Tumor Cell-Derived Exosomes

Exosomes （EXO） derived from dendritic cells （DC） and tumor cells have been used to stimulate antitumor immune responses in animal models and in clinical trials. However, there has been no side-by-side comparison of the stimulatory efficiency of the antitumor immune responses induced by these two commonly used EXO vaccines. In this study, we selected to study the phenotype characteristics of EXO derived from a transfected EG7 tumor cells expressing ovalbumin （OVA） and OVA-pulsed DC by flow cytometry. We compared the stimulatory effect in induction of OVA-specific immune responses between these two types of EXO. We found that OVA protein-pulsed DCOVA-derived EXO （EXODC） can more efficiently stimulate naive OVA-specific CD8^＋ T cell proliferation and differentiation into cytotoxic T lymphocytes in vivo, and induce more efficient antitumor immunity than EG7 tumor cell-derived EXO （EXOEG7）. In addition, we elucidated the important role of the host DC in EXO vaccines that the stimulatory effect of EXO is delivered to T cell responses by the host DC. Therefore, DC-derived EXO may represent a more effective EXO-based vaccine in induction of antitumor immunity. Cellular ＆ Molecular Immunology. 2006;3（3）：205-211.