Pub Date : 2025-12-26DOI: 10.1016/j.tice.2025.103295
Heba F. Ibrahim , Eman H. Thabet , Sara Assem , Basma Mady , Soha Elatrebi , Manal Ahmed Ali , Eiman I. Zaki
Chronic pancreatitis is a critical health problem that is usually complicated by pancreatic fibrosis and diabetes mellitus. Nicotine is a considerable etiological risk factor for this condition. Our research was constructed to explore and compare between the possible therapeutic roles of adipose tissue- derived mesenchymal stem cells (AT- MSCs) and puerarin (Pue) in improving nicotine-induced pancreatic fibrosis. Rats were randomly distributed into: group I; control rats and group II; nicotine- treated rats. Group II was further divided into; model, AT-MSCs- treated, Pue-treated and withdrawal groups. Weight gain study and intraperitoneal glucose tolerance tests were assessed. Pancreatic tissue was processed for measurement of amylase, lipase, interleukin- 6, malondialdehyde and superoxide dismutase. Furthermore, quantitative RT-PCR of caspase-3, transforming growth factor-beta1 (TGF- β1), alpha-smooth muscle actin (α-SMA) and collagen I, was performed. Histopathological, immunohistochemical and ultra-structural examinations were conducted as well. We found that administration of AT- MSCs and Pue helped to increase insulin secretion and suppress inflammatory oxidative stress parameters. In addition, apoptosis and fibrosis were receded through declining of caspase-3 and elements of TGF-β1/α-SMA/collagen I fibrotic pathway. The pancreatic architecture was restored to a great extent. However, AT-MSCs caused a marked pancreatic improvement and regeneration when compared to Pue which resulted in only a moderate amelioration. Insignificant and difficultly detectable spontaneous recovery was noticed in the withdrawal group. Both AT-MSCs and Pue have a promising effectiveness as targeted therapeutic agents against nicotine- induced pancreatic fibrosis, with a higher efficiency of AT- MSCs.
{"title":"Adipose tissue- derived mesenchymal stem cells versus puerarin for ameliorating nicotine- induced pancreatic fibrosis in rats","authors":"Heba F. Ibrahim , Eman H. Thabet , Sara Assem , Basma Mady , Soha Elatrebi , Manal Ahmed Ali , Eiman I. Zaki","doi":"10.1016/j.tice.2025.103295","DOIUrl":"10.1016/j.tice.2025.103295","url":null,"abstract":"<div><div>Chronic pancreatitis is a critical health problem that is usually complicated by pancreatic fibrosis and diabetes mellitus. Nicotine is a considerable etiological risk factor for this condition. Our research was constructed to explore and compare between the possible therapeutic roles of adipose tissue- derived mesenchymal stem cells (AT- MSCs) and puerarin (Pue) in improving nicotine-induced pancreatic fibrosis. Rats were randomly distributed into: group I; control rats and group II; nicotine- treated rats. Group II was further divided into; model, AT-MSCs- treated, Pue-treated and withdrawal groups. Weight gain study and intraperitoneal glucose tolerance tests were assessed. Pancreatic tissue was processed for measurement of amylase, lipase, interleukin- 6, malondialdehyde and superoxide dismutase. Furthermore, quantitative RT-PCR of caspase-3, transforming growth factor-beta1 (TGF- β1), alpha-smooth muscle actin (α-SMA) and collagen I, was performed. Histopathological, immunohistochemical and ultra-structural examinations were conducted as well. We found that administration of AT- MSCs and Pue helped to increase insulin secretion and suppress inflammatory oxidative stress parameters. In addition, apoptosis and fibrosis were receded through declining of caspase-3 and elements of TGF-β1/α-SMA/collagen I fibrotic pathway. The pancreatic architecture was restored to a great extent. However, AT-MSCs caused a marked pancreatic improvement and regeneration when compared to Pue which resulted in only a moderate amelioration. Insignificant and difficultly detectable spontaneous recovery was noticed in the withdrawal group. Both AT-MSCs and Pue have a promising effectiveness as targeted therapeutic agents against nicotine- induced pancreatic fibrosis, with a higher efficiency of AT- MSCs.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103295"},"PeriodicalIF":2.5,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesicles (EVs) serve as crucial vehicles for the intercellular transfer of bioactive molecules. While the mechanisms of EV biogenesis are well characterized in mammals, they remain comparatively understudied in invertebrates. This knowledge gap is particularly notable for the medicinal leech, Hirudo nipponia. In this study, the ultrastructural features of Hirudo nipponia salivary glands in resting and secretory states were analyzed using scanning and transmission electron microscopy to investigate the biogenesis and release of EVs. For the first time, it is demonstrated that salivary gland cells possess dual pathways for EV biogenesis: a classical pathway and a unique pathway derived from secretory granules. These findings provide critical morphological evidence for the conservation of EV biogenesis in invertebrates and highlight a key secretory adaptation for specialized physiological functions.
{"title":"The unique biogenesis pathway of extracellular vesicles in Hirudo nipponia salivary gland cells","authors":"Ya-Li Zhu, Meng-Xiang Jia, Ru-Yu Qu, Qian Li, Xia Qiu, Wen-Chen Zhao, Yuan-Yuan Luo","doi":"10.1016/j.tice.2025.103296","DOIUrl":"10.1016/j.tice.2025.103296","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) serve as crucial vehicles for the intercellular transfer of bioactive molecules. While the mechanisms of EV biogenesis are well characterized in mammals, they remain comparatively understudied in invertebrates. This knowledge gap is particularly notable for the medicinal leech, <em>Hirudo nipponia</em>. In this study, the ultrastructural features of <em>Hirudo nipponia</em> salivary glands in resting and secretory states were analyzed using scanning and transmission electron microscopy to investigate the biogenesis and release of EVs. For the first time, it is demonstrated that salivary gland cells possess dual pathways for EV biogenesis: a classical pathway and a unique pathway derived from secretory granules. These findings provide critical morphological evidence for the conservation of EV biogenesis in invertebrates and highlight a key secretory adaptation for specialized physiological functions.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103296"},"PeriodicalIF":2.5,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Substrate type play a pivotal role in regulating the morphology, mechanical properties, and cytoskeletal organization of cancer cells. In this study, we examined the response of U2OS osteosarcoma cells to substrate stiffness, with a particular focus on cytoskeletal remodeling, cell elasticity, and microparticle internalization. To simulate environments of moderate and high stiffness, cells were cultured on polyacrylamide (PA) hydrogels with a stiffness of 40 kPa and on rigid glass substrates, respectively. Changes in cell morphology and cytoskeletal organization were assessed using fluorescence microscopy, while cell mechanical properties were measured using AFM. To investigate the relationship between substrate mechanics and endocytic activity, carboxylated fluorescent 2 µm latex microspheres were introduced to the cell culture system.
U2OS cells cultured on glass exhibited a significantly larger surface area, more actin stress fibers, and a more organized, stretched cytoskeletal architecture compared to cells grown on 40 kPa PA gels. AFM measurements further demonstrated that cells on glass were mechanically stiffer than those on PA substrates. Microparticle uptake was also strongly influenced by substrate stiffness. Cells cultured on 40 kPa PA gels internalized a significantly greater number of fluorescent microspheres and notably, on 40 kPa PA gel formed “cup-like” structures around the beads, composed of microtubules. Three-dimensional image reconstructions revealed that these structures frequently encapsulate the particles in an asymmetrical manner, indicative of an active cytoskeletal remodeling. To better understand the molecular composition of microtubule-based structures, we analyzed the localization of selected microtubule-associated proteins (MAPs), including IQGAP1, CLIP1, and MARK2. Interestingly, only IQGAP1 was localized prominently to the microtubule cups on 40 kPa gels, often forming ring-like structures surrounding the beads. In some cases, these rings were observed independently of microtubules, suggesting the involvement of IQGAP1 in an active, possibly microtubule-initiated, endocytic process.
In conclusion, our findings demonstrate that substrate type modulates multiple aspects of U2OS cell behavior, including morphology, cytoskeletal arrangement, mechanical properties, and microparticle uptake. These results underscore the mechanosensitive nature of osteosarcoma cells and highlight novel roles for microtubule cup-like structures and MAPs, particularly IQGAP1 in cellular uptake mechanisms.
{"title":"Microtubule-based cup-like structures appear during microparticle uptake in U2OS cells cultured on different substrate types","authors":"Carina Rząca , Agata Kubisiak , Dominik Panek , Marta Targosz-Korecka , Zenon Rajfur","doi":"10.1016/j.tice.2025.103297","DOIUrl":"10.1016/j.tice.2025.103297","url":null,"abstract":"<div><div>Substrate type play a pivotal role in regulating the morphology, mechanical properties, and cytoskeletal organization of cancer cells. In this study, we examined the response of U2OS osteosarcoma cells to substrate stiffness, with a particular focus on cytoskeletal remodeling, cell elasticity, and microparticle internalization. To simulate environments of moderate and high stiffness, cells were cultured on polyacrylamide (PA) hydrogels with a stiffness of 40 kPa and on rigid glass substrates, respectively. Changes in cell morphology and cytoskeletal organization were assessed using fluorescence microscopy, while cell mechanical properties were measured using AFM. To investigate the relationship between substrate mechanics and endocytic activity, carboxylated fluorescent 2 µm latex microspheres were introduced to the cell culture system.</div><div>U2OS cells cultured on glass exhibited a significantly larger surface area, more actin stress fibers, and a more organized, stretched cytoskeletal architecture compared to cells grown on 40 kPa PA gels. AFM measurements further demonstrated that cells on glass were mechanically stiffer than those on PA substrates. Microparticle uptake was also strongly influenced by substrate stiffness. Cells cultured on 40 kPa PA gels internalized a significantly greater number of fluorescent microspheres and notably, on 40 kPa PA gel formed “cup-like” structures around the beads, composed of microtubules. Three-dimensional image reconstructions revealed that these structures frequently encapsulate the particles in an asymmetrical manner, indicative of an active cytoskeletal remodeling. To better understand the molecular composition of microtubule-based structures, we analyzed the localization of selected microtubule-associated proteins (MAPs), including IQGAP1, CLIP1, and MARK2. Interestingly, only IQGAP1 was localized prominently to the microtubule cups on 40 kPa gels, often forming ring-like structures surrounding the beads. In some cases, these rings were observed independently of microtubules, suggesting the involvement of IQGAP1 in an active, possibly microtubule-initiated, endocytic process.</div><div>In conclusion, our findings demonstrate that substrate type modulates multiple aspects of U2OS cell behavior, including morphology, cytoskeletal arrangement, mechanical properties, and microparticle uptake. These results underscore the mechanosensitive nature of osteosarcoma cells and highlight novel roles for microtubule cup-like structures and MAPs, particularly IQGAP1 in cellular uptake mechanisms.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103297"},"PeriodicalIF":2.5,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.tice.2025.103294
Mian Xie , Jiajia Hao , Chen Chao , Xi Chen , Qiuling Chen , Yao-wang Lin , Jiang-hua Li , Qi-yun Liu , Cheng Liu
Objective
Myocardial ischemia-reperfusion injury (MIRI) is a secondary condition following the reestablishment of blood flow to the heart, resulting in myocardial damage such as cardiomyocyte death, ferroptosis, fibrosis, and hypertrophy. However, there is still a lack of targeted therapeutic drugs to date.Aldometanib is a newly developed activator of AMP-activated protein kinase (AMPK) located on the lysosomal membrane, which exhibits significant pharmacological potential. Nevertheless, its role in MIRI remains incompletely understood.
Methods
This study assessed aldometanib's impact on myocardial ischemia-reperfusion injury using H9c2 and AC16 cardiomyocyte lines as in vitro models.
Results
Experimental data demonstrated that aldometanib promoted cardiomyocyte proliferation, reduced oxidative stress, and alleviated inflammatory responses. Furthermore, we identified that aldometanib could inhibit ferroptosis in cardiomyocytes. Mechanistically, our investigations revealed that aldometanib exerted a cardioprotective effect by alleviating cardiomyocyte damage through the regulation of mitochondrial function. Specifically, aldometanib enhanced mitophagy by activating lysosomal AMPK. Additionally, we found that aldometanib exerted an antioxidant effect via Nrf2, thereby mitigating ferroptosis. In animal models, we preliminarily confirmed that aldometanib treatment attenuated tissue damage and functional impairment following myocardial ischemia-reperfusion, further supporting its therapeutic potential.
Conclusions
This study uncovers the protective effect of aldometanib against MIRI and its underlying mechanism, providing experimental evidence and a potential candidate drug for targeting MIRI.
{"title":"Aldometanib attenuates OGD/R-induced cardiomyocyte injury via mitigation of mitochondrial dysfunction","authors":"Mian Xie , Jiajia Hao , Chen Chao , Xi Chen , Qiuling Chen , Yao-wang Lin , Jiang-hua Li , Qi-yun Liu , Cheng Liu","doi":"10.1016/j.tice.2025.103294","DOIUrl":"10.1016/j.tice.2025.103294","url":null,"abstract":"<div><h3>Objective</h3><div>Myocardial ischemia-reperfusion injury (MIRI) is a secondary condition following the reestablishment of blood flow to the heart, resulting in myocardial damage such as cardiomyocyte death, ferroptosis, fibrosis, and hypertrophy. However, there is still a lack of targeted therapeutic drugs to date.Aldometanib is a newly developed activator of AMP-activated protein kinase (AMPK) located on the lysosomal membrane, which exhibits significant pharmacological potential. Nevertheless, its role in MIRI remains incompletely understood.</div></div><div><h3>Methods</h3><div>This study assessed aldometanib's impact on myocardial ischemia-reperfusion injury using H9c2 and AC16 cardiomyocyte lines as <em>in vitro</em> models.</div></div><div><h3>Results</h3><div>Experimental data demonstrated that aldometanib promoted cardiomyocyte proliferation, reduced oxidative stress, and alleviated inflammatory responses. Furthermore, we identified that aldometanib could inhibit ferroptosis in cardiomyocytes. Mechanistically, our investigations revealed that aldometanib exerted a cardioprotective effect by alleviating cardiomyocyte damage through the regulation of mitochondrial function. Specifically, aldometanib enhanced mitophagy by activating lysosomal AMPK. Additionally, we found that aldometanib exerted an antioxidant effect via Nrf2, thereby mitigating ferroptosis. In animal models, we preliminarily confirmed that aldometanib treatment attenuated tissue damage and functional impairment following myocardial ischemia-reperfusion, further supporting its therapeutic potential.</div></div><div><h3>Conclusions</h3><div>This study uncovers the protective effect of aldometanib against MIRI and its underlying mechanism, providing experimental evidence and a potential candidate drug for targeting MIRI.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103294"},"PeriodicalIF":2.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The incorporation of nanoparticles into hydrogels enhances their properties for biomedical applications. Strontium can enhance osteogenesis through osteoblast formation by substituting calcium in osteoblast-mediated processes.
Materials and methods
Collagen-gelatin hydrogels (COL-GEL) were synthesized with and without strontium fluorophosphate (SrFP) to study their effect on osteogenic differentiation of adipose-derived mesenchymal stem cells (AD-MSCs). Scaffolds were characterized using XRD and FTIR. Biocompatibility of SrFP and scaffolds was assessed using the MTT assay and acridine orange. Their osteogenic differentiation potential was evaluated by ALP activity, calcium content, alizarin red, von Kossa staining, real-time RT-PCR and immunocytochemistry.
Results
SrFP at 50 μg/ml significantly promoted proliferation by 1.5-fold over 3 days. The COL-GEL-0.1 %SrFP scaffold showed higher cell proliferation compared to COL-GEL-0.5 %SrFP. The COL-GEL-SrFP exhibited high ALP activity (1.5-fold enhancement) and calcium content (2.1-fold enhancement), consistent with the results of alizarin red (p ≤ 0.05) and von Kossa (p ≤ 0.01). Gene and protein analyses revealed the elevated levels of ALP, Col-I (1.6-fold), osteocalcin (1.7-fold) and RUNX2 (2.3-fold) gene expression, as well as a significant upregulation of osteocalcin and osteopontin protein levels (more than 3-fold) in the COL-GEL-SrFP after 14 day-differentiation.
Conclusion
Compared to the COL-GEL hydrogel, the COL-GEL-SrFP improved cell-scaffold interactions and demonstrated more effective osteogenic differentiation. These findings suggest that COL-GEL-SrFP represents a promising and biocompatible scaffold for increasing the osteogenic differentiation of AD-MSCs and subsequent mineralization. This study highlights the potential of collagen and gelatin-based hydrogels incorporated with SrFP nanoparticles as a novel alternative to current therapeutic approaches in bone regenerative medicine.
{"title":"Engineering bone regeneration: Strontium fluorophosphate, incorporation into collagen and gelatin-based hydrogels promotes osteogenesis in human adipose-derived mesenchymal stem cells","authors":"Sahel Noori , Faezeh Norouz , Raheleh Halabian , Hossein Aghamollaei , Elahe Eftekhari , Ali Salimi","doi":"10.1016/j.tice.2025.103292","DOIUrl":"10.1016/j.tice.2025.103292","url":null,"abstract":"<div><h3>Background</h3><div>The incorporation of nanoparticles into hydrogels enhances their properties for biomedical applications. Strontium can enhance osteogenesis through osteoblast formation by substituting calcium in osteoblast-mediated processes.</div></div><div><h3>Materials and methods</h3><div>Collagen-gelatin hydrogels (COL-GEL) were synthesized with and without strontium fluorophosphate (SrFP) to study their effect on osteogenic differentiation of adipose-derived mesenchymal stem cells (AD-MSCs). Scaffolds were characterized using XRD and FTIR. Biocompatibility of SrFP and scaffolds was assessed using the MTT assay and acridine orange. Their osteogenic differentiation potential was evaluated by ALP activity, calcium content, alizarin red, von Kossa staining, real-time RT-PCR and immunocytochemistry.</div></div><div><h3>Results</h3><div>SrFP at 50 μg/ml significantly promoted proliferation by 1.5-fold over 3 days. The COL-GEL-0.1 %SrFP scaffold showed higher cell proliferation compared to COL-GEL-0.5 %SrFP. The COL-GEL-SrFP exhibited high ALP activity (1.5-fold enhancement) and calcium content (2.1-fold enhancement), consistent with the results of alizarin red (<em>p</em> ≤ 0.05) and von Kossa (<em>p</em> ≤ 0.01). Gene and protein analyses revealed the elevated levels of ALP, Col-I (1.6-fold), osteocalcin (1.7-fold) and RUNX2 (2.3-fold) gene expression, as well as a significant upregulation of osteocalcin and osteopontin protein levels (more than 3-fold) in the COL-GEL-SrFP after 14 day-differentiation.</div></div><div><h3>Conclusion</h3><div>Compared to the COL-GEL hydrogel, the COL-GEL-SrFP improved cell-scaffold interactions and demonstrated more effective osteogenic differentiation. These findings suggest that COL-GEL-SrFP represents a promising and biocompatible scaffold for increasing the osteogenic differentiation of AD-MSCs and subsequent mineralization. This study highlights the potential of collagen and gelatin-based hydrogels incorporated with SrFP nanoparticles as a novel alternative to current therapeutic approaches in bone regenerative medicine.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103292"},"PeriodicalIF":2.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The simultaneous epidemic of obesity and type 2 diabetes is driven by insulin resistance, chronic inflammation, and progressive β-cell dysfunction within an obese, lipotoxic microenvironment. Conventional therapies may improve glycemic control but rarely reverse the underlying metabolic damage or restore long-term homeostasis. Regenerative strategies based on stem cells such as mesenchymal stem cells (MSCs), adipose-derived stem cells (ASCs), and induced pluripotent stem cells (iPSCs), together with their extracellular vesicles (EVs) and exosomes have emerged as promising approaches to address both β-cell failure and obesity-related pathology. These interventions may restore β-cell mass and function, enhance insulin sensitivity, and remodel dysfunctional adipose tissue through direct cell replacement and paracrine signaling. This review emphasizes integrated strategies that combine stem cells, exosomes, pharmacological agents, and tissue-engineering platforms (3-D scaffolds, hydrogels, and exosome delivery systems) to achieve synergistic and more durable metabolic benefits in diabesity. Particular focus is placed on how these combinations address adipose tissue inflammation and fibrosis, ectopic lipid accumulation, brown/beige adipose tissue dysfunction, and enhance glycemic control indices. Although preclinical and early-phase clinical studies are encouraging, major challenges remain in achieving scalable manufacturing, immunological compatibility, product standardization, targeted delivery, and long-term safety. We critically discuss the pathophysiology of diabesity, highlighting current and future directions in stem cells and exosome-based therapies for developing safe, effective, and sustainable treatment strategies for diabesity.
{"title":"Integrated strategies from stem cells to exosomes for amelioration of insulin resistance and promoting β-cell regeneration in diabesity","authors":"Himadri Singh , Rakesh Bhaskar , Shampa Ghosh , Pradeep Kumar Mishra , Krishna Kumar Singh , Jitendra Kumar Sinha , Sung Soo Han","doi":"10.1016/j.tice.2025.103293","DOIUrl":"10.1016/j.tice.2025.103293","url":null,"abstract":"<div><div>The simultaneous epidemic of obesity and type 2 diabetes is driven by insulin resistance, chronic inflammation, and progressive β-cell dysfunction within an obese, lipotoxic microenvironment. Conventional therapies may improve glycemic control but rarely reverse the underlying metabolic damage or restore long-term homeostasis. Regenerative strategies based on stem cells such as mesenchymal stem cells (MSCs), adipose-derived stem cells (ASCs), and induced pluripotent stem cells (iPSCs), together with their extracellular vesicles (EVs) and exosomes have emerged as promising approaches to address both β-cell failure and obesity-related pathology. These interventions may restore β-cell mass and function, enhance insulin sensitivity, and remodel dysfunctional adipose tissue through direct cell replacement and paracrine signaling. This review emphasizes integrated strategies that combine stem cells, exosomes, pharmacological agents, and tissue-engineering platforms (3-D scaffolds, hydrogels, and exosome delivery systems) to achieve synergistic and more durable metabolic benefits in diabesity. Particular focus is placed on how these combinations address adipose tissue inflammation and fibrosis, ectopic lipid accumulation, brown/beige adipose tissue dysfunction, and enhance glycemic control indices. Although preclinical and early-phase clinical studies are encouraging, major challenges remain in achieving scalable manufacturing, immunological compatibility, product standardization, targeted delivery, and long-term safety. We critically discuss the pathophysiology of diabesity, highlighting current and future directions in stem cells and exosome-based therapies for developing safe, effective, and sustainable treatment strategies for diabesity.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103293"},"PeriodicalIF":2.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reduced weight bearing during growth can induce bony morphological characteristics of developmental dysplasia of the hip, a risk factor for hip osteoarthritis (OA). However, the long-term effects of reloading remain unknown. This study aimed to evaluate the immediate and long-term effects of hindlimb suspension (HS) during growth on hip bone morphology, alignment, and histopathology. Four-week-old female rats were subjected to HS for four or eight weeks to reduce weight bearing. After 4 or 8 weeks of HS, the rats were reloaded until 54 weeks of age, which corresponds to human middle age. Age-matched animals served as controls. Bone morphology and alignment parameters were measured using three-dimensional reconstructed images from X-ray computed tomography. A histopathological analysis of the femoral head was also performed. Immediately after four and eight weeks of HS, increased femoral anteversion (FeAV) and acetabular anteversion (AcAV), as well as decreased femoral head diameter (characteristics of hip OA), were detected. After reloading until 54 weeks of age, these features persisted, and an increase of distraction index, which are indicators of structural instability, appeared in rats after 4 and/or 8weeks of HS. Furthermore, OA-like changes, such as articular cartilage thinning and subchondral bone sclerosis, were observed in the femoral head after long-term reloading. Additionally, FeAV was significantly correlated with several histopathological indices of femoral head cartilage. These results suggest that reduced weight bearing during growth may lead to hip morphological and alignment abnormalities, which could result in limited OA-like hip joint changes in the long term.
{"title":"Immediate and long-term effects of insufficient weight-bearing during growth on hip morphology and histopathology in rats","authors":"Marina Kanehara, Norikazu Nishida, Akinori Kaneguchi, Junya Ozawa","doi":"10.1016/j.tice.2025.103289","DOIUrl":"10.1016/j.tice.2025.103289","url":null,"abstract":"<div><div>Reduced weight bearing during growth can induce bony morphological characteristics of developmental dysplasia of the hip, a risk factor for hip osteoarthritis (OA). However, the long-term effects of reloading remain unknown. This study aimed to evaluate the immediate and long-term effects of hindlimb suspension (HS) during growth on hip bone morphology, alignment, and histopathology. Four-week-old female rats were subjected to HS for four or eight weeks to reduce weight bearing. After 4 or 8 weeks of HS, the rats were reloaded until 54 weeks of age, which corresponds to human middle age. Age-matched animals served as controls. Bone morphology and alignment parameters were measured using three-dimensional reconstructed images from X-ray computed tomography. A histopathological analysis of the femoral head was also performed. Immediately after four and eight weeks of HS, increased femoral anteversion (FeAV) and acetabular anteversion (AcAV), as well as decreased femoral head diameter (characteristics of hip OA), were detected. After reloading until 54 weeks of age, these features persisted, and an increase of distraction index, which are indicators of structural instability, appeared in rats after 4 and/or 8weeks of HS. Furthermore, OA-like changes, such as articular cartilage thinning and subchondral bone sclerosis, were observed in the femoral head after long-term reloading. Additionally, FeAV was significantly correlated with several histopathological indices of femoral head cartilage. These results suggest that reduced weight bearing during growth may lead to hip morphological and alignment abnormalities, which could result in limited OA-like hip joint changes in the long term.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103289"},"PeriodicalIF":2.5,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-21DOI: 10.1016/j.tice.2025.103290
Fariba Aghaei , Ehsan Arabzadeh , Foad Feizolahi , Ali Nejati Bezdi , Majid Abasi , Mehdi Zargani
Background
This paper inspects the influence of 8-week endurance swimming supplemented with vitamin C and Silymarin on histopathological changes and some gene markers of skeletal muscle hypertrophy in aged rats receiving a high-fat diet (HFD).
Methods
Twenty-five aged male Wistar rats underwent random allocation to five groups, including a normal diet (Control), HFD, HFD + combined vitamin C and Silymarin supplementation (HFD+CS), HFD + endurance swimming (HFD+ES), and HFD + CS + ES. After six weeks of HFD, CS was gavaged to rats as the selected intervention together with HFD in the supplementation groups over eight weeks. Besides, the exercise groups received swimming exercise training five days/week over eight weeks.
Results
HFD increased the lipid profile and fat penetration into the liver tissue of elderly rats. Meanwhile, endurance swimming exercises and a combined supplement significantly improved the liver tissue and regulated the lipid profile. The examination of muscle tissue and gene changes revealed that HFD could increase muscle atrophy and reduce the 4E-BP1, S6K1, and mTOR gene levels, while the combination of exercise and supplementation could increase the 4E-BP1, S6K1, and IGF-1 gene levels and improve muscle fiber diameter in aged rats.
Conclusion
Endurance swimming training with vitamin C and silymarin supplementation in aging NAFLD model rats can improve lipid profile factors and skeletal muscle tissue fiber diameter.
{"title":"Boosting muscle health in aging rats: The synergistic effect of vitamin C, silymarin, and endurance swimming on a high-fat diet","authors":"Fariba Aghaei , Ehsan Arabzadeh , Foad Feizolahi , Ali Nejati Bezdi , Majid Abasi , Mehdi Zargani","doi":"10.1016/j.tice.2025.103290","DOIUrl":"10.1016/j.tice.2025.103290","url":null,"abstract":"<div><h3>Background</h3><div>This paper inspects the influence of 8-week endurance swimming supplemented with vitamin C and Silymarin on histopathological changes and some gene markers of skeletal muscle hypertrophy in aged rats receiving a high-fat diet (HFD).</div></div><div><h3>Methods</h3><div>Twenty-five aged male Wistar rats underwent random allocation to five groups, including a normal diet (Control), HFD, HFD + combined vitamin C and Silymarin supplementation (HFD+CS), HFD + endurance swimming (HFD+ES), and HFD + CS + ES. After six weeks of HFD, CS was gavaged to rats as the selected intervention together with HFD in the supplementation groups over eight weeks. Besides, the exercise groups received swimming exercise training five days/week over eight weeks.</div></div><div><h3>Results</h3><div>HFD increased the lipid profile and fat penetration into the liver tissue of elderly rats. Meanwhile, endurance swimming exercises and a combined supplement significantly improved the liver tissue and regulated the lipid profile. The examination of muscle tissue and gene changes revealed that HFD could increase muscle atrophy and reduce the 4E-BP1, S6K1, and mTOR gene levels, while the combination of exercise and supplementation could increase the 4E-BP1, S6K1, and IGF-1 gene levels and improve muscle fiber diameter in aged rats.</div></div><div><h3>Conclusion</h3><div>Endurance swimming training with vitamin C and silymarin supplementation in aging NAFLD model rats can improve lipid profile factors and skeletal muscle tissue fiber diameter.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103290"},"PeriodicalIF":2.5,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-21DOI: 10.1016/j.tice.2025.103291
Tengyan Zhu , Shuzhen Fang , Xiaoqin Shang
Pressure ulcer (PU) is defined as localized tissue damage caused by prolonged pressure on any part of the body. Oroxindin (Oro) exhibits significant anti-inflammatory and anti-cancer effects. This study aimed to investigate the effect and underlying mechanism of Oro on PU. Angiogenesis was detected by CD31 immunohistochemistry and CD31/α-SMA immunofluorescence staining in vivo. Cell scratch assay, Transwell assay, and tube formation assay were performed to assess cell migration and angiogenesis in vitro. Phospho-kinase array was used to identify the pathway in Oro-treated human umbilical vein endothelial cells (HUVECs), and the mechanism was investigated by Western blot, luciferase reporter gene assay, biolayer interferometry assay, and molecular docking. Results showed that Oro accelerated wound healing and angiogenesis in the PU mouse model. Moreover, Oro promoted cell migration and tube formation in HUVECs. In addition, Oro activated the PI3K/AKT signaling pathway through the suppression of PTEN. PTEN overexpression reversed the effects of Oro on cell migration and tube formation in HUVECs. In conclusion, we demonstrated that Oro promoted PU wound healing in vivo and facilitated angiogenesis in HUVECs through activation of the PI3K/AKT signaling pathway via PTEN suppression, indicating the potential of Oro as an effective treatment for PU.
{"title":"Oroxindin promotes angiogenesis in pressure ulcers through activating PI3K/AKT signaling pathway by PTEN suppression","authors":"Tengyan Zhu , Shuzhen Fang , Xiaoqin Shang","doi":"10.1016/j.tice.2025.103291","DOIUrl":"10.1016/j.tice.2025.103291","url":null,"abstract":"<div><div>Pressure ulcer (PU) is defined as localized tissue damage caused by prolonged pressure on any part of the body. Oroxindin (Oro) exhibits significant anti-inflammatory and anti-cancer effects. This study aimed to investigate the effect and underlying mechanism of Oro on PU. Angiogenesis was detected by CD31 immunohistochemistry and CD31/α-SMA immunofluorescence staining in vivo. Cell scratch assay, Transwell assay, and tube formation assay were performed to assess cell migration and angiogenesis in vitro. Phospho-kinase array was used to identify the pathway in Oro-treated human umbilical vein endothelial cells (HUVECs), and the mechanism was investigated by Western blot, luciferase reporter gene assay, biolayer interferometry assay, and molecular docking. Results showed that Oro accelerated wound healing and angiogenesis in the PU mouse model. Moreover, Oro promoted cell migration and tube formation in HUVECs. In addition, Oro activated the PI3K/AKT signaling pathway through the suppression of PTEN. PTEN overexpression reversed the effects of Oro on cell migration and tube formation in HUVECs. In conclusion, we demonstrated that Oro promoted PU wound healing in vivo and facilitated angiogenesis in HUVECs through activation of the PI3K/AKT signaling pathway via PTEN suppression, indicating the potential of Oro as an effective treatment for PU.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103291"},"PeriodicalIF":2.5,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-21DOI: 10.1016/j.tice.2025.103288
Dada Yao, Huaqiang Zhou, Qichen Chen
Background
Lung cancer (LC) is a prevalent and lethal malignancy with limited treatments for advanced stages. The aim was to investigate the outcome of prophylactic adoption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in advanced LC patients on the basis of concurrent chemoradiotherapy. Methods: A total of 150 patients with advanced LC who received concurrent chemoradiotherapy at The Third People’s Hospital of Yuhang District between April 2023 and April 2025 were randomly assigned to two groups: an observation group (AG) and a control group (BG). Subjects were treated with platinum-based doublet chemotherapy combined with intensity-modulated conformal radiotherapy. AG received prophylactic rhG-CSF administration within 24–72 h after chemotherapy. The white blood cell (WBC) count, neutrophil (NEU) count, immune function indicators, inflammatory factor levels, and clinical efficacy were compared. Results: Following treatment, the WBC and NEU counts in AG were higher as against BG; CD4+ T cells was higher, while CD8+ T cells, CD3+PD-1 T cells, etc., were lower in AG as against BG; IL-10, IL-6, and TNF-α in AG were lower as against BG; objective response rate (ORR) (44.0 %) and disease control rate (DCR) (88.0 %) in AG were elevated as against BG (26.7 %, 64.0 %) (P < 0.05). Conclusion: Prophylactic adoption of rhG-CSF during concurrent chemoradiotherapy in advanced LC patients can protect hematopoietic function, regulate immune balance, reduce inflammatory response, and improve clinical efficacy.
{"title":"Efficacy of prophylactic adoption of recombinant human granulocyte colony-stimulating factor in advanced lung cancer patients after chemotherapy","authors":"Dada Yao, Huaqiang Zhou, Qichen Chen","doi":"10.1016/j.tice.2025.103288","DOIUrl":"10.1016/j.tice.2025.103288","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer (LC) is a prevalent and lethal malignancy with limited treatments for advanced stages. The aim was to investigate the outcome of prophylactic adoption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in advanced LC patients on the basis of concurrent chemoradiotherapy. Methods: A total of 150 patients with advanced LC who received concurrent chemoradiotherapy at The Third People’s Hospital of Yuhang District between April 2023 and April 2025 were randomly assigned to two groups: an observation group (AG) and a control group (BG). Subjects were treated with platinum-based doublet chemotherapy combined with intensity-modulated conformal radiotherapy. AG received prophylactic rhG-CSF administration within 24–72 h after chemotherapy. The white blood cell (WBC) count, neutrophil (NEU) count, immune function indicators, inflammatory factor levels, and clinical efficacy were compared. Results: Following treatment, the WBC and NEU counts in AG were higher as against BG; CD4<sup>+</sup> T cells was higher, while CD8<sup>+</sup> T cells, CD3<sup>+</sup>PD-1 T cells, etc., were lower in AG as against BG; IL-10, IL-6, and TNF-α in AG were lower as against BG; objective response rate (ORR) (44.0 %) and disease control rate (DCR) (88.0 %) in AG were elevated as against BG (26.7 %, 64.0 %) (<em>P</em> < 0.05). Conclusion: Prophylactic adoption of rhG-CSF during concurrent chemoradiotherapy in advanced LC patients can protect hematopoietic function, regulate immune balance, reduce inflammatory response, and improve clinical efficacy.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103288"},"PeriodicalIF":2.5,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}