作者: Xiao, Zexiu ; Fu, Qingling ; Fang, Qiannan ; Wu, Wenbin ; Xu, Xiang ; Liang, Rongzhen ; Sun, Jianbo ; Wang, Julie ; Zeng, Donglan ; Zheng, Yue ; Zheng, Song Guo ; Yuan, Jia ; Lai, Tianwen ; Su, Wenru

Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b⁺CD11c⁺ proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases.

2024-04-01·Journal of Advanced Research

Infusion of GMSCs relieves autoimmune arthritis by suppressing the externalization of neutrophil extracellular traps via PGE2-PKA-ERK axis

Article

作者: Dang, Junlong ; Xiong, Yiding ; Shao, Yiming ; Chen, Ye ; Sun, Jianbo ; Yuan, Jia ; Liu, Yu ; Liu, Yan ; Zeng, Donglan ; Shi, Xiaoyi ; Cai, Wei ; Zhao, Jun ; Zheng, Song Guo ; Chen, Jingrong ; Hou, Yuluan ; Cai, Peihong ; Brand, David D ; Li, Siwen ; Wu, Wenbin

INTRODUCTIONRheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B × N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA. Human gingival-derived mesenchymal stem cells (GMSCs) have been previously shown to possess immunosuppressive effects in arthritis and humanized animal models. However, it is unknown whether GMSCs can manage neutrophils in autoimmune arthritis.OBJECTIVESTo evaluate whether infusion of GMSCs can alleviate RA by regulating neutrophils and NETs formation. If this is so, we will explore the underlying mechanism(s) in an animal model of inflammatory arthritis.METHODSThe effects of GMSCs on RA were assessed by comparing the symptoms of the K/B × N serum transfer-induced arthritis (STIA) model administered either with GMSCs or with control cells. Phenotypes examined included clinical scores, rear ankle thickness, paw swelling, inflammation, synovial cell proliferation, and immune cell frequency. The regulation of GMSCs on NETs was examined through immunofluorescence and immunoblotting in GMSCs-infused STIA mice and in an in vitro co-culture system of neutrophils with GMSCs. The molecular mechanism(s) by which GMSCs regulate NETs was explored both in vitro and in vivo by silencing experiments.RESULTSWe found in this study that adoptive transfer of GMSCs into STIA mice significantly ameliorated experimental arthritis and reduced neutrophil infiltration and NET formation. In vitro studies also showed that GMSCs inhibited the generation of NETs in neutrophils. Subsequent investigations revealed that GMSCs secreted prostaglandin E2 (PGE2) to activate protein kinase A (PKA), which ultimately inhibited the downstream extracellular signal-regulated kinase (ERK) pathway that is essential for NET formation.CONCLUSIONOur results demonstrate that infusion of GMSCs can ameliorate inflammatory arthritis mainly by suppressing NET formation via the PGE2-PKA-ERK signaling pathway. These findings further support the notion that the manipulation of GMSCs is a promising stem cell-based therapy for patients with RA and other autoimmune and inflammatory diseases.

2023-12-01·Journal of Periodontology

Stem‐cell based soft tissue substitutes: Engineering of crosslinked polylysine‐hyaluronic acid microspheres ladened with gingival mesenchymal stem cells for collagen tissue regeneration and angiogenesis

Article

作者: Li, Chaolun ; Li, Mengdi ; Xi, Hongwei ; Zhong, Zhe ; Ni, Jing ; Wu, Yiqun

AbstractBackgroundThe aim of this study was to construct crosslinked polylysine‐hyaluronic acid microspheres (pl‐HAM) ladened with gingival mesenchymal stem cells (GMSCs) and explore its biologic behavior in soft tissue regeneration.MethodsThe effects of the crosslinked pl‐HAM on the biocompatibility and the recruitment of L‐929 cells and GMSCs were detected in vitro. Moreover, the regeneration of subcutaneous collagen tissue, angiogenesis and the endogenous stem cells recruitment were investigated in vivo. We also detected the cell developing capability of pl‐HAMs.ResultsThe crosslinked pl‐HAMs appeared to be completely spherical‐shaped particles and had good biocompatibility. L‐929 cells and GMSCs grew around the pl‐HAMs and increased gradually. Cell migration experiments showed that pl‐HAMs combined with GMSCs could promote the migration of vascular endothelial cells significantly. Meanwhile, the green fluorescent protein‐GMSCs in the pl‐HAM group still remain in the soft tissue regeneration area 2 weeks after surgery. The results of in vivo studies showed that denser collagen deposition and more angiogenesis‐related indicator CD31 expression in the pl‐HAMs+ GMSCs + GeL group compared with the pl‐HAMs + GeL group. Immunofluorescence showed that CD44, CD90, CD73 co‐staining positive cells surrounded the microspheres in both pl‐HAMs + GeL group and pl‐HAM + GMSCs + GeL group.ConclusionsThe crosslinked pl‐HAM ladened with GMSCs system could provide a suitable microenvironment for collagen tissue regeneration, angiogenesis and endogenous stem cells recruitment, which may be an alternative to autogenous soft tissue grafts for minimally invasive treatments for periodontal soft tissue defects in the future.

项与 OSSM-007 相关的新闻（医药）

2023-05-01

·Pharmaceutical Technology

CIRM grants funds to Ossium Health for OSSM-007 development

Micrographs of grades of skin graft-versus-host-disease. Credit: Sakhila Ghimire, Daniela Weber, Emily Mavin,Xiao nong Wang,Anne Mary Dickinson and Ernst Holler1 / commons.wikimedia.org. The California Institute of Regenerative Medicine (CIRM) has awarded $3.46m Clinical Stage Research Programme (CLIN1) grant to Ossium Health for advancing OSSM-007 development to treat steroid-refractory acute graft versus host disease (GVHD). OSSM-007 is the interferon-gamma primed mesenchymal stem cell product of Ossium Health. The grant will help in expediting pre-clinical and manufacturing activities of the product. The company intends to commence clinical study activities by the end of this year. Acute GVHD occurs following allogeneic hematopoietic stem cell transplants (HCT). It is a reaction where immunocompetent donor cells (the graft) identify and attack the tissues of a recipient. According to Ossium Health, nearly 30 to 60% allogeneic HCT recipients develop acute GVHD and approximately half of them will become refractory to systemic steroid therapy. Ossium Health CEO and co-founder Kevin Caldwell said: “We’re thrilled to partner with CIRM and appreciate their ongoing commitment to advancing research in stem cell-based therapeutics. “This grant will accelerate Ossium’s development of OSSM-007 and is a crucial step towards a powerful new treatment option for patients with GVHD.” The company uses its deceased donor bone marrow banking platform for developing cell therapies. These therapies are being assessed to treat orthopaedic trauma, haematologic diseases, and organ rejection. In March this year, the US Food and Drug Administration (FDA) accepted Ossium Health’s Investigational New Drug (IND) application for OSSM-001 to treat refractory perianal fistulas in Crohn’s disease patients. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva. Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. By Cytiva Thematic By downloading this case study, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy