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Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute promyelocytic leukemia

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Frontiers of Medicine 2017年第3期11卷 410-422页

作者： Dan Huang Yan Yang Jian Sun Xiaorong Dong Jiao Wang Hongchen Liu Chengquan Lu Xueyu Chen Jing Shao Jinsong Yan Dalian Key Laboratory of Hematology Liaoning Hematopoietic Stem Cell Transplantation Medical Center Department of Hematology ofthe Second Hospital of Dalian Medical University Dalian 116027 China Dalian Key Laboratory of Hematology Liaoning HematopoieticStem Cell Transplantation Medical Center Department of Environmental Health and Toxicology School of Public Health Dalian Medical University Dalian 116044 China

Aberrant expression of annexin A2-SI00A10 heterotetramer （AIIt） associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia （APL）, but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor α （PML/RARα） fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5＇-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29 ± 0.13 fold higher than that by control pSG5 vector or wild-type RARer. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation （IRPG） in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid （ATRA） significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.

关键词： annexin A2-S100A10 heterotetramer PML/R.ARa fusion protein plasmin cell invasion acute promyelocytic leukemia

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Future perspectives on cell therapy for autism spectrum disorder

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BIOcell 2022年第4期46卷 873-879页

作者： MAKOTO NABETANI TAKEO MUKAI department of Pediatrics Yodogawa Christian HospitalOsaka533-0024Japan department of cell Processing and transfusion The Institute of Medical ScienceThe University of TokyoTokyo108-8639Japan

Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by impairments in social communication,abnormal to absent verbal communication,the presence of repetitive stereotypic verbal and nonverbal behaviors and restricted interests,with onset early in *** showed cognitive and behavioral characteristics of ASD by impairment of communication,cognition,perception,motor skills,executive function,theory of mind and emotion ***,pathogenesis of immune pathology in the brains of individuals with ASD has been *** therapeutic approaches in the viewpoints of immune modulation and microglial function are logical for novel treatments for individuals with *** therapies such as umbilical cord blood cells and mesenchymal stromal cells for ASD will be a challenging and encouraging field in the future clinical study with progress of biotechnological science.

关键词： Autism ASD cell therapy Umbilical cord blood cells MSC Mesenchymal stromal cells

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Therapeutic applications of bone marrow-derived stem cells in liver transplantation for end-stage liver diseases

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Chinese Science Bulletin 2007年第18期52卷 2449-2456页

作者： LUO HaiYing WANG YunFang KONG Wei PEI XueTao department of Stem cell and Regenerative Medicine Beijing Institute of Transfusion Medicine Beijing 100850 China College of Life Science Jilin University Changchun 130062 China

Today, liver transplantation (LT) is the only established treatment for end-stage liver diseases. The de- velopment of LT, including OLT, cadaveric LT, split LT, living donor LT (LDLT), brings hopes to patients with these diseases. However, increasing donor shortage, rejection and life-long immunosuppression with its side effects are the major limitations of this therapy strategy. Bone marrow-derived stem cells (BMDSCs) are capable of differentiating into hepatocyte-like cells and contribute to liver injury repair. The microenvironment of liver injury caused by rejection, ischemia/reperfusion, loss of liver mass, recurrence of HCV and "small-for-size syndrome" after LT can attract a variety of bone marrow-derived stem cell population to the peripheral circulation and then migration to the injury liver to promote the hepatic function restoration. Additionally, BMDSCs can also take part in the functional regeneration of living donor liver after LDLT. This participation in liver regeneration may be associated to the interac- tion between SDF-1and its receptor CXCR4, involving HGF, IL-8, MMP9, and VEGF/VEGFR-2. BMDSC with its bio-characteristics could maintain the allograft tolerance from different angles and in different ways. In conclusion, BMDSCs transplantation, as a new assistant therapeutic method for LT, will ex- pand the space of LT, and provide more survival opportunities for the patients suffering liver diseases in the future.

关键词：肝移植骨髓干细胞晚期肝病治疗肝功能重建

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Current perspectives on mesenchymal stromal cell therapy for graft versus host disease

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cellular & Molecular Immunology 2023年第6期20卷 613-625页

作者： Nadir Kadri Syivie Amu llen lacobaeus Erik Boberg Katarina Le Blanc department of Laboratory Medicine Karolinska InstitutetStockholmSweden department of Clinical Neuroscience Division of NeurologyKarolinska Institute and Karolinska University HospitalStockholmSweden department of Haematology Karolinska University HospitalStockholmSweden department of cell Therapies and Allogeneic Stem cell transplantation Karolinska University Hospital StockholmSweden

Graft versus host disease(GvHD)is the clinical condition in which bone marrow-derived mesenchymal stromal cells(MsCs)have been most frequently *** this review,we summarize the experience from clinical trials that have paved the way to *** MsC-based therapy has shown an exceptional safety profile,identifying potency assays and disease biomarkers that reliably predict the capacity of a specific MSC batch to alleviate GvHD has been *** GvHD diagnosis and staging are based solely on clinical criteria,individual patients recruited in the same clinical trial may have vastly different underlying biology,obscuring trial outcomes and making it difficult to determine the benefit of MsCs in subgroups of *** accumulating body of evidence indicates the importance of considering not only the cell product but also patient-specific biomarkers and/or immune characteristics in determining MSC responsiveness.A mode of action where intravascular MSC destruction is followed by monocyte-efferocytosis-mediated skewing of the immune repertoire in a permissive inflammatory environment would both explain why cell engraftment is irrelevant for MsC efficacy and stress the importance of biologic differences between responding and nonresponding *** recommend a combined analysis of clinical outcomes and both biomarkers of disease activity and MSC potency assays to identify patients with GvHD who are likely to benefit from MSC therapy.

关键词： MSC GVHD Hematological malignancies acute GVHD chronic GVHD

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In vitro differentiation of human adipose-derived mesenchymal stem cells into endothelial-like cells

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Chinese Science Bulletin 2006年第15期51卷 1863-1868页

作者： GUAN Lidong LI Shaoqing WANG Yunfang YUE Huimin LIU Daqing HE Lijuan BAI Cixian YAN Fang NAN Xue SHI Shuangshuang PEI Xuetao department of Stem cell and Regenerative Medicine Beijing Institute of Transfusion Medicine Beijing 100850 China Stomatology Hospital the Fourth Military Medical University Xi'an 710032 China

The neovascularization of ischemic tis- sue is a crucial initial step for the functional rehabili- tation and wound healing. However, the short of seed cell candidate for the foundation of vascular network is still a big issue. Human adipose tissue derived mesenchymal stem cells (hADSCs), which possess multilineage potential, are capable of adipogenic, osteogenic, and chondrogenic differentiation. We examined whether this kind of stem cells could dif- ferentiate into endothelial-like cells and participate in blood vessel formation, and whether they could be used as an ideal cell source for therapeutic angio- genesis in ischemic diseases or vascularization of tissue constructs. The results showed that hADSCs, grown under appropriately induced conditions, dis- played characteristics similar to those of vessel en- dothelium. The differentiated cells expressed endo- thelial cell markers CD34 and vWF, and had high metabolism of acetylated low-density lipoprotein and prostacyclin. In addition, the induced cells were able to form tube-like structures when cultured on matrigel. Our data indicated that induced hADSCs could ex- hibit characteristics of endothelial cells. Therefore, these cells, as a source of human endothelial cells, may find many applications in such realms as engi- neering blood vessels, endothelial cell transplantation for myocardial regeneration, and induction of angio- genesis for treatment of regional ischemia.

关键词：脂肪组织干细胞内皮细胞组织工程

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Adoptive transfer of T cells transduced with a chimeric antigen receptor to treat relapsed or refractory acute leukemia: efficacy and feasibility of immunotherapy approaches

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Science China(Life Sciences) 2016年第10期59卷 673-677页

作者： Guoliang Ding Hu Chen department of Hematopoietic Stem cell transplantation Affiliated Hospital of Academy of Military Medical Sciences

Treatment outcomes of acute leukemia(AL) have not improved over the past several decades and relapse rates remain high despite the availability of aggressive therapies. Conventional relapsed leukemia treatment includes second allogeneic hematopoietic stem cell transplantation(allo-HSCT) and donor lymphocyte infusion(DLI), which in most cases mediate, at best, a modest graft-versus-leukemia effect, although their clinical efficacy is still limited. Although allo-HSCT following myeloablative conditioning is a curative treatment option for younger patients with acute myeloid leukemia(AML) in a first complete remission(CR), allo-HSCT as a clinical treatment is usually limited because of treatment-related toxicity. The overall DLI remission rate is only 15%–42% and 2-year overall survival(OS) is approximately 15%–20%, with a high(40%–60%) incidence of DLI-related graft-versus-host disease(GVHD). Therefore, development of new, targeted treatment strategies for relapsed and refractory AL patients is ongoing. Adoptive transfer of T cells with genetically engineered chimeric antigen receptors(CARs) is an encouraging approach for treating hematological malignancies. These T cells are capable of selectively recognizing tumor-associated antigens and may overcome many limitations of conventional therapies, inducing remission in patients with chemotherapy-refractory or relapsed AL. In this review, we aimed to highlight the current understanding of this promising treatment modality, discussing its adverse effects and efficacy.

关键词： chimeric antigen receptor acute leukemia efficacy feasibility

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Rationale for the potential use of mesenchymal stromal cells in liver transplantation

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World Journal of Gastroenterology 2014年第44期20卷 16418-16432页

作者： Morgan Vandermeulen Céline Grégoire Alexandra Briquet Chantal Lechanteur Yves Beguin Olivier Detry department of Abdominal Surgery and transplantation CHU Liege University of Liege department of Hematology CHU Liege University of Liege Laboratory of cell and Gene Therapy CHU Liege University of Liege

Mesenchymal stromal cells (MSCs) are multipotent and self-renewing cells that reside essentially in the bone marrow as a non-hematopoietic cell population, but may also be isolated from the connective tissues of most organs. MSCs represent a heterogeneous population of adult, fibroblast-like cells characterized by their ability to differentiate into tissues of mesodermal lineages including adipocytes, chondrocytes and osteocytes. For several years now, MSCs have been evaluated for their in vivo and in vitro immunomodulatory and ‘tissue reconstruction’ properties, which could make them interesting in various clinical settings, and particularly in organ transplantation. This paper aims to review current knowledge on the properties of MSCs and their use in pre-clinical and clinical studies in solid organ transplantation, and particularly in the field of liver transplantation. The first available clinical data seem to show that MSCs are safe to use, at least in the medium-term, but more time is needed to evaluate the potential adverse effects of long-term use. Many issues must be resolved on the correct use of MSCs. Intensive in vitro and pre-clinical research are the keys to a better understanding of the way that MSCs act, and to eventually lead to clinical success.

关键词： Mesenchymal stem cells Organ transplantation Complication Immunosuppression Tolerance

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Dynamic Expression of bFGF and TGFβ2 in Glomus cell Grafts of Carotid Body in Rat Model of Parkinson Disease

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第4期23卷 380-382,395页

作者：曹学兵孙圣刚刘洪涛童萼塘夏穗生 department of Neurology Institute of Organic transplantation

To investigate the changes in the expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFβ2) in glomus cell grafts of carotid body in the rat model of 6 hydroxydopamine induced Parkinson disease, immunohistochemical staining of bFGF and TGFβ2 in the sections of striate body was done on the 2nd, 4th and 12th week after transplantation. The results showed that on the 2nd week after transplantation, bFGF annd TGFβ2 were not detectable in the glumous cell grafts. On the 4th week after graft, bFGF and TGFβ2 immunoreactivity was increased within the grafts and at the graft host interface but was restricted only to astrocytes. In the striatum surrounding the graft, bFGF was expressed persistently, while TGFβ2 showed transient expression. It was suggested that the transient expression of TGFβ2 was likely due more to the trauma imposed by the graft procedure than to an intrinsic. The deficiency in astrocytic bFGF early after graft may be responsible for the poor survival of grafted glomus cells of carotid body.

关键词： basic fibroblast growth factor transforming growth factor beta 2 graft glomus cell carotid body

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Mesenchymal stem cells in tissue repairing and regeneration: Progress and future

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Burns & Trauma 2013年第1期1卷 13-20页

作者： Jiafei Xi Xinlong Yan Junnian Zhou Wen Yue Xuetao Pei Stem cell and Regenerative Medicine Lab Beijing Institute of Transfusion Medicine Beijing China

The presence of mesenchymal progenitor cells within bone marrow has been known since the late nineteenth century. To date, mesenchymal stem cells (MSCs) have been isolated from several different connective tissues, such as adipose tissue, muscle, placenta, umbilical cord matrix, blood, liver, and dental pulp. Bone marrow, however, is still one of the major sources of MSCs for preclinical and clinical research. MSCs were first evaluated for regenerative applications and have since been shown to directly influence the immune system and to promote neovascularization of ischemic tissues. These observations have prompted a new era of MSC transplantation as a treatment for various diseases. In this review, we summarize the important studies that have investigated the use of MSCs as a therapeutic agent for regenerative medicine, immune disorders, cancer, and gene therapy. Furthermore, we discuss the mechanisms involved in MSC-based therapies and clinical-grade MSC manufacturing.

关键词： Mesenchymal stem cells regenerative medicine gene therapy anticancer immune disorder

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Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization

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World Journal of Stem cells 2024年第3期16卷 287-304页

作者： Fei Liu Jing Xiao Lei-Hui Chen Yu-Yue Pan Jun-Zhang Tian Zhi-Ren Zhang Xiao-Chun Bai School of Basic Medical Sciences Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina department of Health Management Guangdong Second Provincial General HospitalGuangzhou 510317Guangdong ProvinceChina Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai People’s Hospital Affiliated with Jinan UniversityZhuhai 519000Guangdong ProvinceChina Centre of Reproduction Development and AgingFaculty of Health SciencesUniversity of MacaoMacao 999078China department of Stomatology Guangdong Second Provincial General HospitalGuangzhou 510317Guangdong ProvinceChina Zhuhai Institute of Translational Medicine Zhuhai Hospital Affiliated with Jinan UniversityZhuhai 519000Guangdong ProvinceChina department of cell Biology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina

BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative *** cells can self-organise into microsized organ units,partially modelling tissue function and *** pulp organoids have been used to recapitulate the processes of tooth development and related ***,the lack of vasculature limits the utility of dental pulp *** To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and *** hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp *** biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were *** The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and ***-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with *** biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of *** In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.

关键词： Human dental pulp stem cells Prevascularized organoids Integrated analyses Angiogenesis Forkhead box protein O1

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