Journal of Pharmacology and Experimental Therapeutics最新文献

{"title":"Follistatin-like protein 1: Implications for renal disease progression.","authors":"Yiqi Gao, Junyi Ren, Haoyu Peng, Moussa Ide Nasser, Chi Liu","doi":"10.1016/j.jpet.2025.103564","DOIUrl":"10.1016/j.jpet.2025.103564","url":null,"abstract":"<p><p>Renal diseases, including glomerulonephritis, acute kidney injury, chronic kidney failure, and kidney tumors are all current global health challenges. Lesions in other systems can cause renal diseases and can affect other systems or even the whole body. Despite ongoing advancements in pharmaceutical and technological innovations, the prognosis for end-stage renal disease, encompassing renal failure and tumors, continues to be bleak. Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein produced mainly by mesenchymal cells. FSTL1 is a glycoprotein that belongs to the family of secreted, cysteine-rich acidic proteins (SPARC). It plays a pivotal role in cell survival, proliferation, differentiation, and migration, as well as in modulating inflammation and immune responses. Research has shown that FSTL1 plays a crucial role in the onset and progression of renal diseases. This review explores the functions and underlying mechanisms of FSTL1 in kidney pathology. SIGNIFICANCE STATEMENT: This review highlights the pivotal role of FSTL1 in renal diseases, particularly its involvement in renal fibrosis, inflammation, and ischemia-reperfusion injury. By elucidating its dual roles across different pathologies, this work underscores FSTL1's potential as both a biomarker and a therapeutic target, offering novel insights for managing chronic kidney disease and associated complications.</p>","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103564"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation of antithrombotic therapies: Beyond conventional drugs.","authors":"Wei Li, Hong Yue","doi":"10.1016/j.jpet.2025.103574","DOIUrl":"10.1016/j.jpet.2025.103574","url":null,"abstract":"","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103574"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental determinants of ketamine's prohedonic and antianhedonic efficacy: Persistence of enhanced reward responsiveness is modulated by chronic stress.","authors":"Amaya R Jenkins, Daniela B Radl, Thomas J Kornecook, Diego A Pizzagalli, Jack Bergman, Derek L Buhl, Patricio O'Donnell, Brian D Kangas","doi":"10.1016/j.jpet.2025.103572","DOIUrl":"10.1016/j.jpet.2025.103572","url":null,"abstract":"<p><p>Ketamine, a dissociative anesthetic with well documented abuse liability, can also provide rapid-onset and persistent antidepressant effects and is currently used for the management of treatment-resistant depression. Although the precise neurobiological mechanisms underlying its antidepressant actions are not fully determined, a critical feature of ketamine's clinical efficacy may be its antianhedonic action. Anhedonia is an endophenotype of depression defined by decreased responsivity to previously rewarding stimuli and is generally not ameliorated by conventional antidepressants, emphasizing the need to examine underlying behavioral mechanisms of action. In this study, the probabilistic reward task, a reverse-translated assay originally designed to objectively quantify anhedonic phenotypes in human subjects, was used in rats to examine ketamine's effects on reward responsiveness under conditions without programmed stressors (3.2-32.0 mg/kg) or during ongoing chronic exposure to ecologically relevant stress (10.0 mg/kg). Results showed that under conditions without programmed stress, ketamine produced significant prohedonic effects in the probabilistic reward task, defined by increases in reward responsiveness that dissipated within 24 hours. In rats exposed to ongoing chronic stress, ketamine produced significant antianhedonic effects, defined by the rescue of blunted reward responsiveness, that persisted for nearly 1 week. Taken together, the prolonged antianhedonic effects of ketamine in rats experiencing chronic stress, compared with the shorter-lived prohedonic effects in subjects without exposure to programmed stressors, are striking and highlight the role of environmental determinants in the effects of ketamine on behavioral processes. Moreover, the translational nature of this experimental design may offer the opportunity to accelerate development of novel antianhedonic therapeutics. SIGNIFICANCE STATEMENT: Although ketamine is used for the management of treatment-resistant depression, its precise behavioral mechanisms of action are not fully delineated. Emerging evidence suggests the attenuation of anhedonia plays a key role in its rapid-acting therapeutic efficacy. To evaluate this possibility, the effects of ketamine were studied using a reverse-translated assay of reward responsiveness in rats and documented to be short-lived (prohedonic) under nonstressful conditions and persistent (antianhedonic) under stressful conditions, informing ketamine effects in healthy versus depressed individuals.</p>","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103572"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histamine H1 Receptor: A potential therapeutic target for pancreatic ductal adenocarcinoma.","authors":"Cristina Salmerón, Elena Tomás Bort, Krishna Sriram, Mehrak Javadi-Paydar, Jane E Smitham, Kimberly Pham, Richard P Grose, Peter J McCormick, Anna DiNardo, Jonathan Weitz, Hervé Tiriac, Andrew M Lowy, Paul A Insel","doi":"10.1016/j.jpet.2025.103573","DOIUrl":"10.1016/j.jpet.2025.103573","url":null,"abstract":"<p><p>Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5-year survival (∼13%). Thus, new, effective, and ideally, less toxic therapies are desperately needed. Epidemiologic studies have found that patients with PDAC prescribed H1-antihistamines have improved survival. Expression of the histamine H1 receptor (HRH1), a G protein-coupled receptor which is blocked by approved H1-antihistamines, is increased by ∼20-fold in PDAC tumors compared with normal pancreas. Here, we used bioinformatic and molecular biological techniques to identify the cellular localization of HRH1 in the PDAC tumor microenvironment, assess functional responses to HRH1 activation, and define its potential biological roles in PDAC. We found that HRH1 is primarily expressed in cancer cells of PDAC tumors in humans and KPC mice (mice engineered to develop PDAC) and signals via G protein q/11 to increase intracellular Ca²⁺. HRH1 activation increases migration and invasion by PDAC cancer cells. Orally administered fexofenadine, an H1-antihistamine, was bioavailable in the tumors of KPC mice and yielded smaller pancreatic tumor tissue weights and lower expression of immunomodulatory (interleukin 6 and PD-1) and fibrotic (Col1A1) genes than in vehicle-control KPC mice. Thus, PDAC cancer cells express HRH1, which is functional in vitro and in vivo, suggesting that the repurposing of approved H1-antihistamines may be an efficacious and safe therapeutic approach for patients with PDAC. SIGNIFICANCE STATEMENT: Pancreatic ductal adenocarcinoma (PDAC) has a ∼13% 5-year survival rate, highlighting the need for new therapies. The HRH1 (histamine) receptor, associated with poorer survival, is upregulated in PDAC tumors. This study found that HRH1 is functional in PDAC cells, increasing intracellular Ca²⁺ via G_q/11 and promoting tumorigenic responses. KPC mice treated with an H1-antihistamine have reduced pancreas weight and lower proinflammatory and fibrotic markers in PDAC tumors. Thus, HRH1 may be a potential target for repurposing approved H1-antihistamines to treat PDAC.</p>","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103573"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The calcium channel agonist (±)-BAY-K-8644 attenuates the ability of gabapentinoids to increase the potency of fentanyl and heroin and decrease the potency of cocaine and d-methamphetamine to elicit discriminative stimulus effects in rats.","authors":"Takato Hiranita, Amanda K Grisham, Abram E Mijares, Nicholas P Ho, Charles P France","doi":"10.1016/j.jpet.2025.103523","DOIUrl":"10.1016/j.jpet.2025.103523","url":null,"abstract":"<p><p>During the opioid epidemic there has been a significant increase in the number of prescriptions for gabapentinoids (gabapentin and pregabalin), which block the α₂δ-subunit of voltage-gated calcium channels (VGCCs). In rats, gabapentinoids enhance the potency of the mu opioid receptor (MOR) agonists fentanyl and heroin and decrease the potency of the stimulant drugs cocaine and d-methamphetamine to elicit discriminative stimulus effects. Moreover, (±)-BAY-K-8644, a dihydropyridine-type agonist at the α₁-subunit of VGCCs (α₁-VGCCs), prevents the antiallodynic effects of gabapentin in rats. The mechanism(s) of interaction between gabapentinoids and MOR agonists and between gabapentinoids and stimulant drugs is/are unclear. This study tested the following hypotheses: (1) the dihydropyridine-type α₁-VGCC blocker nimodipine increases the potency of MOR agonists to elicit discriminative stimulus effects; and (2) (±)-BAY-K-8644 attenuates the ability of gabapentinoids and nimodipine to increase the potency of MOR agonists to elicit discriminative stimulus effects. In rats trained to discriminate fentanyl (0.0032 mg/kg) or cocaine (3.2 mg/kg) from saline, neither (±)-BAY-K-8644 nor nimodipine elicited significant fentanyl- or cocaine-appropriate responding. (±)-BAY-K-8644 did not significantly alter discrimination dose-effect functions of MOR agonists or stimulant drugs whereas nimodipine dose-dependently shifted the MOR agonist discrimination dose-effect functions to the left and the stimulant drug discrimination dose-effect functions to the right. (±)-BAY-K-8644 dose-dependently attenuated the ability of nimodipine and gabapentinoids to increase the potency of MOR agonists and decrease the potency of stimulant drugs to elicit discriminative stimulus effects. These results suggest that gabapentinoids alter the potency of MOR agonists and stimulant drugs to elicit discriminative stimulus effects via blockade of α₁-VGCCs. SIGNIFICANCE STATEMENT: Prescriptions for gabapentinoids (gabapentin and pregabalin) increased significantly during the opioid epidemic. Using (±)-BAY-K-8644, a dihydropyridine-type agonist at the α₁-subunit of the voltage-gated calcium channel (α₁-VGCC), this study reports that in male and female rats, gabapentinoids increase the potency of fentanyl and heroin and decrease the potency of cocaine and d-methamphetamine to elicit discriminative stimulus effects via blockade of dihydropyridine-binding sites on α₁-VGCC. These results suggest that actions of drugs at α₁-VGCCs contribute to the opioid epidemic and opioid/stimulant co-use.</p>","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103523"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between duration, initiation time, routes, and formulations of menopausal hormone therapy use and Alzheimer disease in women: A systematic review and meta-analysis.","authors":"Qixiang Song, Qi Wang, Dang Wu, Zhe Zhang, Mengyao Chen, Chunying Fu, Meiling Li, Xiaoyi Wang, Yanqing Zhao, Dongshan Zhu","doi":"10.1016/j.jpet.2025.103554","DOIUrl":"10.1016/j.jpet.2025.103554","url":null,"abstract":"<p><p>The purpose of this study was to investigate the effect of menopausal hormone therapy (MHT) on the risk of Alzheimer disease (AD) by examining its duration, initiation time, routes of administration, and formulations through systematic review and meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, and Scopus were searched on March 15, 2023. We selected cohort studies, case-control studies, and randomized controlled trials on the effect of MHT on AD in women. Odds ratio, relative risk, and hazard ratio were extracted. Random-effect models were used to estimate the polled estimates (relative risk [RR] or odds ratio [OR]) and their 95% confidence interval (95% CI). We included 3 randomized controlled trials, 12 cohort studies, and 16 case-control studies. A total of 7,710,379 women were included. Pooled estimates showed that MHT use for 3-5 years (cohort, RR = 0.56, 95% CI: 0.34-0.93) or initiation within 5 years of menopause (cohort, RR = 0.70, 95% CI: 0.49-0.99) reduced the risk of AD. Oral administration reduced AD risk (cohort, RR = 0.42, 95% CI: 0.40-0.44). Combining estrogen and progesterone (case-control, OR = 1.13, 95% CI: 1.05-1.21) or progesterone only (case-control, OR = 1.13, 95% CI: 1.10-1.17) increases AD risk. Tibolone increased AD risk (cohort, RR = 1.04, 95% CI: 1.01-1.07; case-control, OR = 1.07, 95% CI: 1.01-1.14). MHT-protected apolipoprotein E genotype 4 carriers (cohort, RR = 0.13, 95% CI: 0.02-0.90), depressed populations (cohort, RR = 0.85, 95% CI: 0.80-0.90), and Americas (cohort, RR = 0.54, 95% CI: 0.37-0.80; case-control, OR = 0.68, 95% CI: 0.47-0.99) from AD. Using MHT early (within 5 years after menopause) for about 5 years may protect against AD. However, combining estrogen with progesterone, or using progesterone only, could increase AD risk. Oral MHT methods are more effective than transdermal ones in reducing this risk. SIGNIFICANCE STATEMENT: Menopausal hormone therapy (MHT) use within 5 years after menopause could offer protective benefits against Alzheimer disease (AD). A combination of estrogen and progesterone, using progesterone only or tibolone usage was connected with an elevated risk of AD. Oral MHT was more effective than transdermal methods in lowering AD risk. MHT lowered AD risk in apolipoprotein E genotype 4 allele carriers, individuals with depression, and Americans. MHT regimens should be highly personalized.</p>","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103554"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shaken and stirred: Stress and alcohol are a potent mix driving behavior and neuroinflammation.","authors":"Jesse R Schank, Joyce Besheer, Dennis F Lovelock","doi":"10.1016/j.jpet.2025.103576","DOIUrl":"10.1016/j.jpet.2025.103576","url":null,"abstract":"","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103576"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced efficiency of MHC class II tumor neoantigen vaccines with a novel CD4⁺ T-cell helper epitope.","authors":"Qiuli Mao, Yahong Tian, Qiumin Yu, Lingxiao Chen, Li Zhang, Yue Tong, Wenbing Yao, Xiangdong Gao, Hong Tian","doi":"10.1016/j.jpet.2025.103570","DOIUrl":"10.1016/j.jpet.2025.103570","url":null,"abstract":"<p><p>Tumor neoantigens, defined as tumor-specific antigens arising from somatic mutations, have shown great potential as targets for cancer vaccines in clinical studies. However, the number of neoantigens capable of effectively activating immune responses is quite limited. Over the past few decades, tumor neoantigen vaccines based on MHC-I epitopes that activate CD8⁺ T cells have been extensively studied. However, growing evidence suggests that CD4⁺ T cells are important in cancer immunotherapy. In contrast to CD8⁺ T cells, the receptors on CD4⁺ T cells exhibit a wider range of antigen peptide-MHC recognition, which can detect more tumor mutation antigens. In our earlier studies, a nitrated CD4⁺ T-cell epitope (NitraTh) was constructed as a novel CD4⁺ T-cell epitope that can enhance the immunogenicity of multiple tumor antigens. Therefore, we designed vaccines targeting MHC-II neoantigen epitopes using the nitrated T-cell epitope containing immunogenic amino acids. We found that vaccines conjugated with NitraTh exhibited enhanced immunogenicity. Crucially, the NitraTh-modified MHC-II tumor neoantigen vaccines increased the proportion of CD4⁺ T cells that infiltrate tumors and the spleen, elevated the expression of several cytokines with antitumor effects and facilitated the transformation of CD4⁺ T cells into Th1 cells, thereby reducing tumor growth. Additionally, the nitrated epitope has been shown to transform naïve CD4⁺ T cells into effector memory cells, thus facilitating enduring antitumor actions. The strategy of combining nitrated epitopes with MHC-II neoantigen epitopes confirms the significance of CD4⁺ T-cell immunity in cancer and may provide a novel approach for cancer vaccine design. SIGNIFICANCE STATEMENT: This study presents a novel design paradigm for tumor vaccines-combining MHC-II epitopes with nitrated CD4⁺ T-cell epitopes. This approach promotes the differentiation of CD4⁺ T cells toward a Th1 phenotype and generates long-lasting effector memory CD4⁺ T cells. Under the enhanced effects of CD4⁺ T cells, the vaccines we designed achieved superior antitumor efficacy and improved the immunosuppressive tumor microenvironment.</p>","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103570"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation studies and multiomics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.","authors":"William B Lynch, Sophia A Miracle, Stanley I Goldstein, Jacob A Beierle, Rhea Bhandari, Ethan T Gerhardt, Ava Farnan, Binh-Minh Nguyen, Kelly K Wingfield, Ida Kazerani, Gabriel A Saavedra, Olga Averin, Britahny M Baskin, Martin T Ferris, Christopher A Reilly, Andrew Emili, Camron D Bryant","doi":"10.1016/j.jpet.2025.103557","DOIUrl":"10.1016/j.jpet.2025.103557","url":null,"abstract":"<p><p>Sensitivity to the subjective reinforcing properties of opioids has a genetic component and can predict addiction liability of opioid compounds. We previously identified Zhx2 as a candidate gene underlying increased brain concentration of the oxycodone (OXY) metabolite oxymorphone (OMOR) in BALB/cJ (J) versus BALB/cByJ (By) females that could increase OXY state-dependent reward. A large structural intronic variant is associated with a robust reduction of Zhx2 expression in J mice, which we hypothesized enhances OMOR levels and OXY addiction-like behaviors. We tested this hypothesis by restoring the Zhx2 loss-of-function in J mice (mouse endogenous retroviral element knockout) and modeling the loss-of-function variant through knocking out the Zhx2 coding exon (exon 3 knockout [E3KO]) in By mice and assessing brain OXY metabolite levels and behavior. Consistent with our hypothesis, Zhx2 E3KO females showed an increase in brain OMOR levels and OXY-induced locomotor activity. However, contrary to our hypothesis, state-dependent expression of OXY conditioned place preference decreased in E3KO females and increased in E3KO males. We also overexpressed Zhx2 in the livers and brains of J mice and observed Zhx2 overexpression in select brain regions that was associated with reduced OXY state-dependent learning. Integrative transcriptomic and proteomic analysis of E3KO mice identified astrocyte function, cell adhesion, extracellular matrix properties, and endothelial cell functions as pathways influencing brain OXY metabolite concentration and behavior. These results support Zhx2 as a quantitative trait gene underlying brain OMOR concentration that is associated with changes in OXY behavior and implicate potential quantitative trait mechanisms that together inform our overall understanding of Zhx2 in brain function. SIGNIFICANCE STATEMENT: This study validated Zhx2 as a gene whose dysfunction increases brain levels of a highly potent and addictive metabolite of oxycodone, oxymorphone, in a female-specific manner. This result has broad implications for understanding the role of oxycodone metabolism and brain oxymorphone levels in the addiction liability of oxycodone (the active ingredient in OxyContin) and highlights the need for the study of sex differences in opioid metabolism as it relates to the addiction liability of opioids and opioid use disorder.</p>","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 5","pages":"103557"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coculture of mesenchymal stem cells and macrophage: A narrative review.","authors":"Jun Ning, Rajiv Kumar Sah, Jing Wang","doi":"10.1016/j.jpet.2025.103531","DOIUrl":"10.1016/j.jpet.2025.103531","url":null,"abstract":"<p><p>Stem cell transplantation is a promising treatment for repairing damaged tissues, but challenges like immune rejection and ethical concerns remain. Mesenchymal stem cells (MSCs) offer high differentiation potential and immune regulatory activity, showing promise in treating diseases such as gynecological, neurological, and kidney disorders. With scientific progress, MSC applications are overcoming traditional treatment limitations. In MSCs-macrophage coculture, MSCs transform macrophages into anti-inflammatory M2 macrophages, reducing inflammation, whereas macrophages enhance MSCs osteogenic differentiation. This coculture is vital for immune modulation and tissue repair, with models varying by contact type and dimensional arrangements. Factors such as coculture techniques and cell ratios influence outcomes. Benefits include improved heart function, wound healing, reduced lung inflammation, and accelerated bone repair. Challenges include optimizing coculture conditions. This study reviews the methodologies, factors, and mechanisms of MSC-macrophage coculture, providing a foundation for tissue engineering applications. SIGNIFICANCE STATEMENT: This review underlines the significant role of mesenchymal stem cell-macrophage coculture, providing a foundation for tissue engineering application.</p>","PeriodicalId":16798,"journal":{"name":"Journal of Pharmacology and Experimental Therapeutics","volume":"392 4","pages":"103531"},"PeriodicalIF":3.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}