Inflammation and regeneration最新文献

{"title":"Extracellular matrix: the critical contributor to skeletal muscle regeneration-a comprehensive review.","authors":"Khurshid Ahmad, Sibhghatulla Shaikh, Hee Jin Chun, Shahid Ali, Jeong Ho Lim, Syed Sayeed Ahmad, Eun Ju Lee, Inho Choi","doi":"10.1186/s41232-023-00308-z","DOIUrl":"10.1186/s41232-023-00308-z","url":null,"abstract":"<p><p>The regenerative ability of skeletal muscle (SM) in response to damage, injury, or disease is a highly intricate process that involves the coordinated activities of multiple cell types and biomolecular factors. Of these, extracellular matrix (ECM) is considered a fundamental component of SM regenerative ability. This review briefly discusses SM myogenesis and regeneration, the roles played by muscle satellite cells (MSCs), other cells, and ECM components, and the effects of their dysregulations on these processes. In addition, we review the various types of ECM scaffolds and biomaterials used for SM regeneration, their applications, recent advances in ECM scaffold research, and their impacts on tissue engineering and SM regeneration, especially in the context of severe muscle injury, which frequently results in substantial muscle loss and impaired regenerative capacity. This review was undertaken to provide a comprehensive overview of SM myogenesis and regeneration, the stem cells used for muscle regeneration, the significance of ECM in SM regeneration, and to enhance understanding of the essential role of the ECM scaffold during SM regeneration.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"58"},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF-α and IFN-γ prestimulation enhances the therapeutic efficacy of human amniotic epithelial stem cells in chemotherapy-induced ovarian dysfunction.","authors":"Yating Huang, Qiuwan Zhang, Wenjiao Cao, Qinyu Zhang, Lulu Wang, Dongmei Lai","doi":"10.1186/s41232-023-00309-y","DOIUrl":"10.1186/s41232-023-00309-y","url":null,"abstract":"<p><strong>Background: </strong>Exposure to a harsh ovarian microenvironment induced by chemotherapeutic agents seriously affects the remodeling of ovarian function and follicular development, leading to premature ovarian failure or insufficiency (POF/POI). For decades, the effectiveness of stem cell therapies in POI animal models has been intensively studied; however, strategies to enhance the therapeutic effect of stem cells remain challenging.</p><p><strong>Methods: </strong>In this study, we first observed the pathological changes of the ovaries at different time points during chemotherapy, including the number of follicles, granulosa cell proliferation, oxidative stress damage, ovarian fibrosis, and inflammatory reaction. Moreover, we investigated whether activated hAECs stimulated by the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were more effective than native hAECs in repairing ovarian injury induced by chemotherapy.</p><p><strong>Results: </strong>The inhibitory effect of chemotherapy drugs on ovarian granulosa cells (GCs) in growing follicles mainly occurred on day 3 after chemotherapy in a mouse model. Then, continued ovarian injury, including oxidative damage and cell death cascades, resulted in the depletion of follicular reserves and inflammation-related ovarian fibrosis. Cytokine array demonstrated that activated hAECs secreted high levels of paracrine cytokines related to extracellular matrix (ECM) remodeling, angiogenesis, and immunomodulation. An in vivo study showed that the engraftment rate of activated hAECs in damaged ovaries was higher than that of native hAECs. Furthermore, activated hAECs in damaged ovaries had significantly upregulated expression of the antioxidant proteins thioredoxin1/2. In addition, activated hAECs had increased numbers of mature follicles and ameliorated the ovarian microenvironment by promoting angiogenesis and reducing ovarian fibrosis.</p><p><strong>Conclusions: </strong>These results indicated that secondary ovarian damage induced by chemotherapy, including oxidative stress damage, chronic inflammatory response, and ovarian tissue fibrosis should be attended. Prestimulation with the proinflammatory factors TNF-α and IFN-γ could enhance the therapeutic efficacy of hAECs against chemotherapy-induced ovarian dysfunction, which may become a new feasible strategy to improve the therapeutic potential of hAECs in regenerative medicine.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"57"},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prime-boost-type PspA3 + 2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci.","authors":"Chieko Yokota, Kosuke Fujimoto, Natsuko Yamakawa, Masamitsu Kono, Daichi Miyaoka, Masaki Shimohigoshi, Miho Uematsu, Miki Watanabe, Yukari Kamei, Akira Sugimoto, Natsuko Kawasaki, Takato Yabuno, Tomotaka Okamura, Eisuke Kuroda, Shigeto Hamaguchi, Shintaro Sato, Muneki Hotomi, Yukihiro Akeda, Ken J Ishii, Yasuhiro Yasutomi, Kishiko Sunami, Satoshi Uematsu","doi":"10.1186/s41232-023-00305-2","DOIUrl":"10.1186/s41232-023-00305-2","url":null,"abstract":"<p><strong>Background: </strong>Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques.</p><p><strong>Methods: </strong>C57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia.</p><p><strong>Results: </strong>Serum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection.</p><p><strong>Conclusions: </strong>Prime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"55"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107593145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regeneration of joint surface defects by transplantation of allogeneic cartilage: application of iPS cell-derived cartilage and immunogenicity.","authors":"Kengo Abe, Noriyuki Tsumaki","doi":"10.1186/s41232-023-00307-0","DOIUrl":"10.1186/s41232-023-00307-0","url":null,"abstract":"<p><strong>Background: </strong>Because of its poor intrinsic repair capacity, articular cartilage seldom heals when damaged.</p><p><strong>Main body: </strong>Regenerative treatment is expected for the treatment of articular cartilage damage, and allogeneic chondrocytes or cartilage have an advantage over autologous chondrocytes, which are limited in number. However, the presence or absence of an immune response has not been analyzed and remains controversial. Allogeneic-induced pluripotent stem cell (iPSC)-derived cartilage, a new resource for cartilage regeneration, reportedly survived and integrated with native cartilage after transplantation into chondral defects in knee joints without immune rejection in a recent primate model. Here, we review and discuss the immunogenicity of chondrocytes and the efficacy of allogeneic cartilage transplantation, including iPSC-derived cartilage.</p><p><strong>Short conclusion: </strong>Allogeneic iPSC-derived cartilage transplantation, a new therapeutic option, could be a good indication for chondral defects, and the development of translational medical technology for articular cartilage damage is expected.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"56"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107593146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The oral-gut axis: a missing piece in the IBD puzzle.","authors":"Sho Kitamoto, Nobuhiko Kamada","doi":"10.1186/s41232-023-00304-3","DOIUrl":"10.1186/s41232-023-00304-3","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a multifactorial intractable intestinal disease. Focusing on only one facet of the pathogenesis of IBD is insufficient to fully capture the complexity of the disease, and results in limited advance in clinical management. Therefore, it is critical to dissect the interactions amongst the multifarious contributors to the pathogenesis to comprehensively understand its pathology and subsequently improve clinical outcomes. In this context, the systemic interactions between organs, particularly the oral-gut axis mediated by host immune cells and resident microorganisms, have garnered significant attention in IBD research. More specifically, periodontal disease such as periodontitis has been implicated in augmenting intestinal inflammation beyond the confines of the oral cavity. There is mounting evidence suggesting that potentially harmful oral resident bacteria, termed pathobionts, and pro-inflammatory immune cells from the oral mucosa can migrate to the gastrointestinal tract, thereby potentiating intestinal inflammation. This article aims to provide a holistic overview of the causal relationship between periodontal disease and intestinal inflammation. Furthermore, we will discuss potential determinants that facilitate the translocation of oral pathobionts into the gut, a key event underpinning the oral-gut axis. Unraveling the complex dynamics of microbiota and immunity in the oral-gut continuum will lead to a better understanding of the pathophysiology inherent in both oral and intestinal diseases and the development of prospective therapeutic strategies.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"54"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.","authors":"Tina Rauchenwald,&nbsp;Florian Handle,&nbsp;Catherine E Connolly,&nbsp;Antonia Degen,&nbsp;Christof Seifarth,&nbsp;Martin Hermann,&nbsp;Christoph H Tripp,&nbsp;Doris Wilflingseder,&nbsp;Susanne Lobenwein,&nbsp;Dragana Savic,&nbsp;Leo Pölzl,&nbsp;Evi M Morandi,&nbsp;Dolores Wolfram,&nbsp;Ira-Ida Skvortsova,&nbsp;Patrizia Stoitzner,&nbsp;Johannes Haybaeck,&nbsp;Marko Konschake,&nbsp;Gerhard Pierer,&nbsp;Christian Ploner","doi":"10.1186/s41232-023-00302-5","DOIUrl":"10.1186/s41232-023-00302-5","url":null,"abstract":"<p><strong>Background: </strong>Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization. Regenerative cells from the wound periphery contribute to the healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated wound microenvironment.</p><p><strong>Methods: </strong>We examined CD45^-/CD31^-/CD34⁺ preadipocytes and CD68⁺ macrophages in human granulation tissue from pressure ulcers (n=6) using immunofluorescence, immunohistochemistry, and flow cytometry. In vitro, we studied macrophage-preadipocyte interactions using primary human adipose-derived stem cells (ASCs) exposed to conditioned medium harvested from IFNG/LPS (M1)- or IL4/IL13 (M2)-activated macrophages. Macrophages were derived from THP1 cells or CD14⁺ monocytes. In addition to confocal microscopy and flow cytometry, ASCs were analyzed for metabolic (OXPHOS, glycolysis), morphological (cytoskeleton), and mitochondrial (ATP production, membrane potential) changes. Angiogenic properties of ASCs were determined by HUVEC-based angiogenesis assay. Protein and mRNA levels were assessed by immunoblotting and quantitative RT-PCR.</p><p><strong>Results: </strong>CD45^-/CD31^-/CD34⁺ preadipocytes were observed with a prevalence of up to 1.5% of total viable cells in human granulation tissue. Immunofluorescence staining suggested a spatial proximity of these cells to CD68⁺ macrophages in vivo. In vitro, ASCs exposed to M1, but not to M2 macrophage secretome showed a pro-fibrotic response characterized by stress fiber formation, elevated alpha smooth muscle actin (SMA), and increased expression of integrins ITGA5 and ITGAV. Macrophage-secreted IL1B and TGFB1 mediated this response via the PI3K/AKT and p38-MAPK pathways. In addition, ASCs exposed to M1-inflammatory stress demonstrated reduced migration, switched to a glycolysis-dominated metabolism with reduced ATP production, and increased levels of inflammatory cytokines such as IL1B, IL8, and MCP1. Notably, M1 but not M2 macrophages enhanced the angiogenic potential of ASCs.</p><p><strong>Conclusion: </strong>Preadipocyte fate in wound tissue is influenced by macrophage polarization. Pro-inflammatory M1 macrophages induce a pro-fibrotic response in ASCs through IL1B and TGFB1 signaling, while anti-inflammatory M2 macrophages have limited effects. These findings shed light on cellular interactions in chronic wounds and provide important information for the potential therapeutic use of ASCs in human wound healing.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"53"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71416293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCL10 deficiency limits macrophage infiltration, preserves lung matrix, and enables lung growth in bronchopulmonary dysplasia.","authors":"Dharmesh V Hirani, Florian Thielen, Siavash Mansouri, Soula Danopoulos, Christina Vohlen, Pinar Haznedar-Karakaya, Jasmine Mohr, Rebecca Wilke, Jaco Selle, Thomas Grosch, Ivana Mizik, Margarete Odenthal, Cristina M Alvira, Celien Kuiper-Makris, Gloria S Pryhuber, Christian Pallasch, S van Koningsbruggen-Rietschel, Denise Al-Alam, Werner Seeger, Rajkumar Savai, Jörg Dötsch, Miguel A Alejandre Alcazar","doi":"10.1186/s41232-023-00301-6","DOIUrl":"10.1186/s41232-023-00301-6","url":null,"abstract":"<p><p>Preterm infants with oxygen supplementation are at high risk for bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease. Inflammation with macrophage activation is central to the pathogenesis of BPD. CXCL10, a chemotactic and pro-inflammatory chemokine, is elevated in the lungs of infants evolving BPD and in hyperoxia-based BPD in mice. Here, we tested if CXCL10 deficiency preserves lung growth after neonatal hyperoxia by preventing macrophage activation. To this end, we exposed Cxcl10 knockout (Cxcl10^-/-) and wild-type mice to an experimental model of hyperoxia (85% O₂)-induced neonatal lung injury and subsequent regeneration. In addition, cultured primary human macrophages and murine macrophages (J744A.1) were treated with CXCL10 and/or CXCR3 antagonist. Our transcriptomic analysis identified CXCL10 as a central hub in the inflammatory network of neonatal mouse lungs after hyperoxia. Quantitative histomorphometric analysis revealed that Cxcl10^-/- mice are in part protected from reduced alveolar. These findings were related to the preserved spatial distribution of elastic fibers, reduced collagen deposition, and protection from macrophage recruitment/infiltration to the lungs in Cxcl10^-/- mice during acute injury and regeneration. Complimentary, studies with cultured human and murine macrophages showed that hyperoxia induces Cxcl10 expression that in turn triggers M1-like activation and migration of macrophages through CXCR3. Finally, we demonstrated a temporal increase of macrophage-related CXCL10 in the lungs of infants with BPD. In conclusion, our data demonstrate macrophage-derived CXCL10 in experimental and clinical BPD that drives macrophage chemotaxis through CXCR3, causing pro-fibrotic lung remodeling and arrest of alveolarization. Thus, targeting the CXCL10-CXCR3 axis could offer a new therapeutic avenue for BPD.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"52"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of immune-related diseases using patient-derived induced pluripotent stem cells.","authors":"Hirofumi Shoda, Bunki Natsumoto, Keishi Fujio","doi":"10.1186/s41232-023-00303-4","DOIUrl":"10.1186/s41232-023-00303-4","url":null,"abstract":"<p><p>The precise pathogenesis of immune-related diseases remains unclear, and new effective therapeutic choices are required for the induction of remission or cure in these diseases. Basic research utilizing immune-related disease patient-derived induced pluripotent stem (iPS) cells is expected to be a promising platform for elucidating the pathogenesis of the diseases and for drug discovery. Since autoinflammatory diseases are usually monogenic, genetic mutations affect the cell function and patient-derived iPS cells tend to exhibit disease-specific phenotypes. In particular, iPS cell-derived monocytic cells and macrophages can be used for functional experiments, such as inflammatory cytokine production, and are often employed in research on patients with autoinflammatory diseases.On the other hand, the utilization of disease-specific iPS cells is less successful for research on autoimmune diseases. One reason for this is that autoimmune diseases are usually polygenic, which makes it challenging to determine which factors cause the phenotypes of patient-derived iPS cells are caused by. Another reason is that protocols for differentiating some lymphocytes associated with autoimmunity, such as CD4⁺T cells or B cells, from iPS cells have not been well established. Nevertheless, several groups have reported studies utilizing autoimmune disease patient-derived iPS cells, including patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), and systemic sclerosis. Particularly, non-hematopoietic cells, such as fibroblasts and cardiomyocytes, differentiated from autoimmune patient-derived iPS cells have shown promising results for further research into the pathogenesis. Recently, our groups established a method for differentiating dendritic cells that produce interferon-alpha, which can be applied as an SLE pathological model. In summary, patient-derived iPS cells can provide a promising platform for pathological research and new drug discovery in the field of immune-related diseases.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"51"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation.","authors":"Yu Suematsu, Narihito Nagoshi, Munehisa Shinozaki, Yoshitaka Kase, Yusuke Saijo, Shogo Hashimoto, Takahiro Shibata, Keita Kajikawa, Yasuhiro Kamata, Masahiro Ozaki, Kaori Yasutake, Tomoko Shindo, Shinsuke Shibata, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano","doi":"10.1186/s41232-023-00298-y","DOIUrl":"10.1186/s41232-023-00298-y","url":null,"abstract":"<p><strong>Background: </strong>Human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC)-based cell transplantation has emerged as a groundbreaking method for replacing damaged neural cells and stimulating functional recovery, but its efficacy is strongly influenced by the state of the injured spinal microenvironment. This study evaluates the impact of a dual therapeutic intervention utilizing hepatocyte growth factor (HGF) and hiPSC-NS/PC transplantation on motor function restoration following spinal cord injury (SCI).</p><p><strong>Methods: </strong>Severe contusive SCI was induced in immunocompromised rats, followed by continuous administration of recombinant human HGF protein into the subarachnoid space immediately after SCI for two weeks. Acute-phase histological and RNA sequencing analyses were conducted. Nine days after the injury, hiPSC-NS/PCs were transplanted into the lesion epicenter of the injured spinal cord, and the functional and histological outcomes were determined.</p><p><strong>Results: </strong>The acute-phase HGF-treated group exhibited vascularization, diverse anti-inflammatory effects, and activation of endogenous neural stem cells after SCI, which collectively contributed to tissue preservation. Following cell transplantation into a favorable environment, the transplanted NS/PCs survived well, facilitating remyelination and neuronal regeneration in host tissues. These comprehensive effects led to substantial enhancements in motor function in the dual-therapy group compared to the single-treatment groups.</p><p><strong>Conclusions: </strong>We demonstrate that the combined therapeutic approach of HGF preconditioning and hiPSC-NS/PC transplantation enhances locomotor functional recovery post-SCI, highlighting a highly promising therapeutic strategy for acute to subacute SCI.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"50"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testosterone upregulates glial cell line-derived neurotrophic factor (GDNF) and promotes neuroinflammation to enhance glioma cell survival and proliferation.","authors":"Kouminin Kanwore, Konimpo Kanwore, Xiaoxiao Guo, Ying Xia, Han Zhou, Lin Zhang, Gabriel Komla Adzika, Adu-Amankwaah Joseph, Ayanlaja Abdulrahman Abiola, Peipei Mu, Piniel Alphayo Kambey, Marie Louis N'dzie Noah, DianShuai Gao","doi":"10.1186/s41232-023-00300-7","DOIUrl":"10.1186/s41232-023-00300-7","url":null,"abstract":"<p><strong>Background: </strong>Testosterone contributes to male organism development, such as bone density, muscle development, and fat repartition. Estrogen (derived from testosterone) also contributes to female reproductive system development. Here, we investigated the effect of testosterone on glioma cells and brain neuron inflammation essential for cancer development and progression.</p><p><strong>Methods: </strong>The human astrocyte and glioma cell lines were treated with 6 ng/ml exogenous testosterone in vitro. We performed cell counting kit-8, transwell, and wound healing assays to determine the effect of testosterone on glioma cell proliferation, migration, and invasion. The glioma cells were injected into the xenograft and treated with 5 µl concentrated testosterone. Transcriptional suppression of glial cell line-derived neurotrophic factor (GDNF) was performed to evaluate brain neuron inflammation and survival. The tumor tissues were assessed by hematoxylin-eosin staining and immunohistochemistry.</p><p><strong>Results: </strong>Testosterone upregulates GDNF to stimulate proliferation, migration, and invasion of glioma cells. Pathologically, the augmentation of GDNF and cyclophilin A contributed to neuroprotection when treated with testosterone. Our investigation showed that testosterone contributes to brain neuron and astrocyte inflammation through the upregulation of nuclear factor erythroid 2-related factor 2 (NRF2), glial fibrillary acid protein (GFAP), and sirtuin 5 (SIRT5), resulting in pro-inflammatory macrophages recruitments into the neural microenvironment. Mechanically, testosterone treatment regulates GDNF translocation from the glioma cells and astrocyte nuclei to the cytoplasm.</p><p><strong>Conclusion: </strong>Testosterone upregulates GDNF in glioma cells and astrocytes essential for microglial proliferation, migration, and invasion. Testosterone contributes to brain tumor growth via GDNF and inflammation. The contribution of testosterone, macrophages, and astrocytes, in old neuron rescue, survival, and proliferation. During brain neuron inflammation, the organism activates and stimulates the neuron rescue through the enrichment of the old neuron microenvironment with growth factors such as GDNF, BDNF, SOX1/2, and MAPK secreted by the surrounding neurons and glial cells to maintain the damaged neuron by inflammation alive even if the axon is dead. The immune response also contributes to brain cell survival through the secretion of proinflammatory cytokines, resulting in inflammation maintenance. The rescued old neuron interaction with infiltrated macrophages contributes to angiogenesis to supplement the old neuron with more nutrients leading to metabolism activation and surrounding cell uncontrollable cell growth.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"49"},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}