Mesenchymal stem cells (MSCs) exhibit unique properties that make them promising candidates for cell therapy, particularly in neurological disorders. They can be derived from various tissues, with bone marrow, adipose tissue, umbilical cord, and placenta being the most common sources. Evidence suggests that the tissue of origin significantly influences MSC characteristics, including secretome composition, proliferation rate, and adhesion capacity.
Clinical trials have demonstrated the safety and therapeutic potential of MSCs in conditions such as spinal cord injury, multiple sclerosis, and stroke. MSC therapy has been associated with improvements in motor, sensory, and cognitive functions, as well as enhanced quality of life. Mechanistically, MSCs promote neuroprotection, reduce inflammation, and modulate immune responses. In spinal cord injury, intrathecal administration of adipose- and bone marrow-derived MSCs has led to significant functional recovery, with single high-dose treatments often yielding better outcomes than multiple lower doses. In amyotrophic lateral sclerosis, bone marrow-derived MSCs have shown potential in slowing disease progression, though higher doses do not always result in greater benefits. In multiple sclerosis, high doses of umbilical cord-derived MSCs improved quality of life and prevented disease progression, whereas lower doses of bone marrow-derived MSCs provided limited functional benefits.
While MSC therapy is considered safe, patient responses vary, and a definitive correlation between administered dose and therapeutic effects remains elusive. The small number of studies using comparable protocols impedes comparison of other relevant factor, limits the drawing of conclusions and underscore the importance of developing standardized protocols to optimize MSC-based treatments and maximize their clinical efficacy.
{"title":"Mesenchymal stem cells in neurological disorders: Insights from clinical trials","authors":"Beatriz Araújo , Inês Serrenho , Andreia Valente da Silva , Bragança Moisés Marceta , Graça Baltazar","doi":"10.1016/j.reth.2025.10.020","DOIUrl":"10.1016/j.reth.2025.10.020","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) exhibit unique properties that make them promising candidates for cell therapy, particularly in neurological disorders. They can be derived from various tissues, with bone marrow, adipose tissue, umbilical cord, and placenta being the most common sources. Evidence suggests that the tissue of origin significantly influences MSC characteristics, including secretome composition, proliferation rate, and adhesion capacity.</div><div>Clinical trials have demonstrated the safety and therapeutic potential of MSCs in conditions such as spinal cord injury, multiple sclerosis, and stroke. MSC therapy has been associated with improvements in motor, sensory, and cognitive functions, as well as enhanced quality of life. Mechanistically, MSCs promote neuroprotection, reduce inflammation, and modulate immune responses. In spinal cord injury, intrathecal administration of adipose- and bone marrow-derived MSCs has led to significant functional recovery, with single high-dose treatments often yielding better outcomes than multiple lower doses. In amyotrophic lateral sclerosis, bone marrow-derived MSCs have shown potential in slowing disease progression, though higher doses do not always result in greater benefits. In multiple sclerosis, high doses of umbilical cord-derived MSCs improved quality of life and prevented disease progression, whereas lower doses of bone marrow-derived MSCs provided limited functional benefits.</div><div>While MSC therapy is considered safe, patient responses vary, and a definitive correlation between administered dose and therapeutic effects remains elusive. The small number of studies using comparable protocols impedes comparison of other relevant factor, limits the drawing of conclusions and underscore the importance of developing standardized protocols to optimize MSC-based treatments and maximize their clinical efficacy.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 1024-1035"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuroinflammation is a key contributor to the pathogenesis of Alzheimer's disease (AD), and impaired clearance of amyloid-β (Aβ) by microglia is closely associated with disease progression. Oxytocin (OXT), a hypothalamic neuropeptide, has recently been reported to exert anti-inflammatory effects on microglia; however, its therapeutic potential in the human brain remains unclear.
Methods
We generated human cerebral organoids (hCOs) from induced pluripotent stem cells (iPSCs) to model early AD-like pathology. Aβ toxicity was induced by applying 3 μM Aβ1–42 for 48 h. The protective effects of OXT were evaluated through immunohistochemistry, RT-qPCR, calcium imaging, and multielectrode array (MEA) recordings. The involvement of microglia in Aβ clearance was assessed by immunostaining and gene expression analysis of TREM2.
Results
Aβ exposure led to significant deposition of Aβ in the outer layers of hCOs, accompanied by suppressed neural activity and increased apoptotic signaling. Pretreatment with OXT attenuated Aβ deposition and caspase-3-mediated apoptosis in a concentration-dependent manner. OXT also restored calcium oscillations and neuronal network activity as measured by MEA. Notably, OXT enhanced the recruitment of microglia to Aβ deposits and upregulated the expression of TREM2, a key regulator of microglial phagocytosis. Co-expression of oxytocin receptors (OXTR) on Iba1-positive microglia suggests that OXT directly modulates microglial activation and Aβ clearance.
Conclusions
OXT has neuroprotective effects on human cortical organoids by preserving their neuronal activity and promoting microglial-mediated Aβ clearance. This study provides novel insights into the therapeutic potential of OXT for targeting neuroinflammation and Aβ pathology in patients with AD.
神经炎症是阿尔茨海默病(AD)发病的关键因素,小胶质细胞对淀粉样蛋白-β (a β)的清除受损与疾病进展密切相关。催产素(OXT)是一种下丘脑神经肽,最近被报道对小胶质细胞具有抗炎作用;然而,它在人脑中的治疗潜力尚不清楚。方法利用诱导多能干细胞(iPSCs)生成人脑类器官(hCOs),模拟早期ad样病理。3 μM a - β1 - 42作用48 h诱导Aβ毒性,通过免疫组织化学、RT-qPCR、钙显像和多电极阵列(MEA)记录评价OXT的保护作用。通过免疫染色和TREM2基因表达分析评估小胶质细胞在Aβ清除中的作用。结果sa β暴露导致hCOs外层Aβ显著沉积,并伴有神经活性抑制和凋亡信号通路增加。OXT预处理以浓度依赖的方式减弱a β沉积和caspase-3介导的细胞凋亡。经MEA测量,OXT还能恢复钙振荡和神经网络活动。值得注意的是,OXT增强了小胶质细胞对a β沉积物的募集,并上调了TREM2的表达,TREM2是小胶质细胞吞噬的关键调节因子。催产素受体(OXTR)在iba1阳性小胶质细胞上的共表达表明,OXT直接调节小胶质细胞的激活和Aβ清除。结论soxt对人皮质类器官具有神经保护作用,其机制是维持类器官的神经元活性,促进小胶质介导的Aβ清除。这项研究为OXT靶向AD患者的神经炎症和Aβ病理的治疗潜力提供了新的见解。
{"title":"Human iPSC-derived cerebral organoids reveal oxytocin-mediated protection against amyloid-β pathology","authors":"Tomoki Asaba, Sayuri Hamano, Ayaka Nanmo, Jieun Seo, Tatsuto Kageyama, Junji Fukuda","doi":"10.1016/j.reth.2025.06.013","DOIUrl":"10.1016/j.reth.2025.06.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Neuroinflammation is a key contributor to the pathogenesis of Alzheimer's disease (AD), and impaired clearance of amyloid-β (Aβ) by microglia is closely associated with disease progression. Oxytocin (OXT), a hypothalamic neuropeptide, has recently been reported to exert anti-inflammatory effects on microglia; however, its therapeutic potential in the human brain remains unclear.</div></div><div><h3>Methods</h3><div>We generated human cerebral organoids (hCOs) from induced pluripotent stem cells (iPSCs) to model early AD-like pathology. Aβ toxicity was induced by applying 3 μM Aβ<sub>1–42</sub> for 48 h. The protective effects of OXT were evaluated through immunohistochemistry, RT-qPCR, calcium imaging, and multielectrode array (MEA) recordings. The involvement of microglia in Aβ clearance was assessed by immunostaining and gene expression analysis of TREM2.</div></div><div><h3>Results</h3><div>Aβ exposure led to significant deposition of Aβ in the outer layers of hCOs, accompanied by suppressed neural activity and increased apoptotic signaling. Pretreatment with OXT attenuated Aβ deposition and caspase-3-mediated apoptosis in a concentration-dependent manner. OXT also restored calcium oscillations and neuronal network activity as measured by MEA. Notably, OXT enhanced the recruitment of microglia to Aβ deposits and upregulated the expression of TREM2, a key regulator of microglial phagocytosis. Co-expression of oxytocin receptors (OXTR) on Iba1-positive microglia suggests that OXT directly modulates microglial activation and Aβ clearance.</div></div><div><h3>Conclusions</h3><div>OXT has neuroprotective effects on human cortical organoids by preserving their neuronal activity and promoting microglial-mediated Aβ clearance. This study provides novel insights into the therapeutic potential of OXT for targeting neuroinflammation and Aβ pathology in patients with AD.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 259-267"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-12DOI: 10.1016/j.reth.2025.08.001
Shahad Ahmed Daood , Martha Then Xin Yi , Nicole Wen Ce Mun , Sharjeel Ilyas , Lee Yin Shien , Oh Jia En , Syed Saad Bin Qasim , Yichen Dai , Galvinderjeet Kaur Grewal , Ng Mei Liit , Gopu Sriram , Malikarjuna Rao Pichika , Kit-Kay Mak , Ranjeet Ajit Bapat , Zeeshan Sheikh , Umer Daood
This paper describes a promising candidate molecule, investigates the pattern of scaffold composition which arises and assesses the effect of the agent on its mechanical properties.
Methods
Scaffold samples were fabricated using a commercial extrusion bioprinter equipped with a pneumatic printhead fitted with a 21G conical nozzle. The Pore Printability Index, and the area and perimeter of the pore within the grid patterns were quantified using ImageJ software (NIH, USA). Mechanical properties of scaffolds were assessed using atomic force microscopy. The phase composition and crystal structures were analyzed using X-ray diffraction and Raman mapping. Morphologies of human gingival fibroblastic cells were examined using scanning electron microscopy. Lactobacillus biofilms were generated for cytolysin peptide cleavage. A rabbit bone defect model with scaffold implantations was used to provide histologic specimens for measuring percentages of bone trabeculae, collagen fibers and inflammatory cells along with granulation tissue. The Primeway Total RNA Extraction Kit was used for RNA extraction.
Results
All bioink formulations demonstrated successful printing of 3D grid and solid square patterned scaffolds achieving Pr values exceeding 0.9. 0.1%K21 group showed the highest elastic modulus. XRD revealed a pattern producing around 90 % β-tricalcium phosphate displaying two peaks at 2θ angles. 0.1 % K21 and 0.1%CHX did not alter scaffold's pore size and porosity. 0.1%K21 group exhibited highest ratio (62.5 ± 6.1 θ), significantly surpassing control. Surface morphologies of cells were also well retained. TEM image shows a sequence of structural changes in fibroblastic cell structure when exposed to K21. 0.1 % K21 proved to be critical in completely eradicating the biofilm. 0.K21 group closed the openings of wound areas completely. Correlation coefficient of gene expression levels demonstrates sample variations and recurring instances among groupings.
Conclusion
3D-printing technologies with 0.1%K21 represent a significant advancement over conventional regenerative medicine techniques for bone-related treatments.
{"title":"From an Antimicrobial Agent to a constituent of 3D Printed Heterogenous Scaffolds Stimulating Bone Characteristics: An In-vitro and Animal model evaluation","authors":"Shahad Ahmed Daood , Martha Then Xin Yi , Nicole Wen Ce Mun , Sharjeel Ilyas , Lee Yin Shien , Oh Jia En , Syed Saad Bin Qasim , Yichen Dai , Galvinderjeet Kaur Grewal , Ng Mei Liit , Gopu Sriram , Malikarjuna Rao Pichika , Kit-Kay Mak , Ranjeet Ajit Bapat , Zeeshan Sheikh , Umer Daood","doi":"10.1016/j.reth.2025.08.001","DOIUrl":"10.1016/j.reth.2025.08.001","url":null,"abstract":"<div><div>This paper describes a promising candidate molecule, investigates the pattern of scaffold composition which arises and assesses the effect of the agent on its mechanical properties.</div></div><div><h3>Methods</h3><div>Scaffold samples were fabricated using a commercial extrusion bioprinter equipped with a pneumatic printhead fitted with a 21G conical nozzle. The Pore Printability Index, and the area and perimeter of the pore within the grid patterns were quantified using ImageJ software (NIH, USA). Mechanical properties of scaffolds were assessed using atomic force microscopy. The phase composition and crystal structures were analyzed using X-ray diffraction and Raman mapping. Morphologies of human gingival fibroblastic cells were examined using scanning electron microscopy. Lactobacillus biofilms were generated for cytolysin peptide cleavage. A rabbit bone defect model with scaffold implantations was used to provide histologic specimens for measuring percentages of bone trabeculae, collagen fibers and inflammatory cells along with granulation tissue. The Primeway Total RNA Extraction Kit was used for RNA extraction.</div></div><div><h3>Results</h3><div>All bioink formulations demonstrated successful printing of 3D grid and solid square patterned scaffolds achieving Pr values exceeding 0.9. <sub><strong>0.1</strong> <strong>%</strong></sub><strong>K21</strong> group showed the highest elastic modulus. XRD revealed a pattern producing around 90 % β-tricalcium phosphate displaying two peaks at 2θ angles. 0.1 % K21 and <sub><strong>0.1</strong> <strong>%</strong></sub><strong>CHX</strong> did not alter scaffold's pore size and porosity. <sub><strong>0.1</strong> <strong>%</strong></sub><strong>K21</strong> group exhibited highest ratio (62.5 ± 6.1 θ), significantly surpassing control. Surface morphologies of cells were also well retained. TEM image shows a sequence of structural changes in fibroblastic cell structure when exposed to K21. 0.1 % K21 proved to be critical in completely eradicating the biofilm. <strong><sub>0.</sub>K21</strong> group closed the openings of wound areas completely. Correlation coefficient of gene expression levels demonstrates sample variations and recurring instances among groupings.</div></div><div><h3>Conclusion</h3><div>3D-printing technologies with <sub><strong>0.1</strong> <strong>%</strong></sub><strong>K21</strong> represent a significant advancement over conventional regenerative medicine techniques for bone-related treatments.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 558-574"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-06-18DOI: 10.1016/j.reth.2025.06.004
Meifang Yin , Jie Xiao , Guangtao Huang , Huanyu Xie , Hongwei Liu , Jianqiang Yuan , Xiaofang Liu , Anna Chiarini , Ubaldo Armato , Ilaria Dal Prà , Shumaila Ijaz , Naziat Begum , Lingyun Wang , Jun Wu
Introduction
Endothelial cell aging is strongly associated with mitochondrial dysfunction, particularly the disruption of mitochondrial-nuclear retrograde communication (MNRC), which is essential for sustaining cellular homeostasis and regulating crucial cellular processes. Nanosecond pulsed electric fields (nsPEF) were shown to exert biological effects by targeting mitochondria. However, the nsPEF regulation of MNRC is still unclear.
Methods
In this study, we set up an in vitro model of d-galactose-induced senescence in human umbilical vein endothelial cells (HUVECs) to investigate the effects of nsPEF treatment on oxidative stress, cell proliferation, mitochondrial membrane potential, and markers of MNRC (MNRC), including HIF-1α and SIRT1. Moreover, we conducted in vivo animal experiments to evaluate nsPEF treatment's effects on HIF-1α and SIRT1 protein expression in endothelial cells (ECs) of in vivo rodents' aging/senescing skin tissue, as well as to examine any later changes in vascular density within the skin.
Results
In vitro results showed that nsPEF treatment suppressed d-galactose-induced senescing effects as they rescued mitochondrial membrane potential, and activated HIF-1α and SIRT1. These effects were confirmed by concurrent reductions in SA-β-Gal activity and in ROS production, and increases in EdU-positive (DNA-synthesizing) cells. Our data showed that nsPEF treatments rescued endothelial cells from d-galactose senescence. Interestingly, nsPEF selectively targeted senescing cells at the tested dose, with no detectable effect on otherwise untreated (normal) HUVECs. In vivo nsPEF treatments upregulated the expression of HIF-1α and SIRT1 in ECs and promoted neoangiogenesis in aged/senescent rodents' skin.
Conclusions
These findings suggest that nsPEF treatments rescue ECs from aging by restoring MNRC, highlighting its potential as a therapeutic strategy for age-related vascular diseases.
{"title":"Nanosecond pulsed electric field applications rejuvenate aging endothelial cells by rescuing mitochondrial-to-nuclear retrograde communication","authors":"Meifang Yin , Jie Xiao , Guangtao Huang , Huanyu Xie , Hongwei Liu , Jianqiang Yuan , Xiaofang Liu , Anna Chiarini , Ubaldo Armato , Ilaria Dal Prà , Shumaila Ijaz , Naziat Begum , Lingyun Wang , Jun Wu","doi":"10.1016/j.reth.2025.06.004","DOIUrl":"10.1016/j.reth.2025.06.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Endothelial cell aging is strongly associated with mitochondrial dysfunction, particularly the disruption of mitochondrial-nuclear retrograde communication (MNRC), which is essential for sustaining cellular homeostasis and regulating crucial cellular processes. Nanosecond pulsed electric fields (nsPEF) were shown to exert biological effects by targeting mitochondria. However, the nsPEF regulation of MNRC is still unclear.</div></div><div><h3>Methods</h3><div>In this study, we set up an <em>in vitro</em> model of <span>d</span>-galactose-induced senescence in human umbilical vein endothelial cells (HUVECs) to investigate the effects of nsPEF treatment on oxidative stress, cell proliferation, mitochondrial membrane potential, and markers of MNRC (MNRC), including HIF-1α and SIRT1. Moreover, we conducted <em>in vivo</em> animal experiments to evaluate nsPEF treatment's effects on HIF-1α and SIRT1 protein expression in endothelial cells (ECs) of <em>in vivo</em> rodents' aging/senescing skin tissue, as well as to examine any later changes in vascular density within the skin.</div></div><div><h3>Results</h3><div>In vitro results showed that nsPEF treatment suppressed <span>d</span>-galactose-induced senescing effects as they rescued mitochondrial membrane potential, and activated HIF-1α and SIRT1. These effects were confirmed by concurrent reductions in SA-β-Gal activity and in ROS production, and increases in EdU-positive (DNA-synthesizing) cells. Our data showed that nsPEF treatments rescued endothelial cells from <span>d</span>-galactose senescence. Interestingly, nsPEF selectively targeted senescing cells at the tested dose, with no detectable effect on otherwise untreated (normal) HUVECs. In vivo nsPEF treatments upregulated the expression of HIF-1α and SIRT1 in ECs and promoted neoangiogenesis in aged/senescent rodents' skin.</div></div><div><h3>Conclusions</h3><div>These findings suggest that nsPEF treatments rescue ECs from aging by restoring MNRC, highlighting its potential as a therapeutic strategy for age-related vascular diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 207-216"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced therapy medicinal products (ATMPs) represent a groundbreaking category of medications that utilize biological-based products to treat or replace damaged organs. It offers potential solutions for complex diseases through gene therapy, somatic cell therapy, tissue engineering, and combined therapies. Although ATMPs have offered significant improvement for a variety of severe illnesses, their progressive development is faced with numerous challenges. Some of these challenges are current complexities in their manufacturing, such as scaling up, scaling out, product efficacy, packaging, storage, stability, and logistic concerns. Other challenges include manufacturing, efficacy, and scaling up of ATMPs, as well as establishing Good Manufacturing Practice (GMP)-compliant processes that align with product specifications derived from non-clinical studies conducted under Good Laboratory Practice (GLP). Additionally, safety concerns such as tumorigenesis are potential. Regulatory and ethical concerns, along with the need for standardization and clear clinical guidelines, are also critical obstacles. To address these challenges, novel technologies such as organoids, artificial intelligence, dynamic culture systems, and biobanking are being explored, providing new opportunities to enhance the consistency, scalability, and precision of ATMP production. Development in artificial intelligence (AI) technology helped scientists to address monitoring concerns, automation, and data management. Introducing advanced guidelines in biobanking helps researchers to overcome the storage and stability concerns. Organoid technology holds a significant promise in overcoming the challenges associated with preclinical and modeling of ATMPs by providing more accurate models for diseases, drug screening, and personalized medicine. This article reviews the current challenges in ATMP manufacturing and application, highlights the advancements in technology that are paving the way for improved therapeutic strategies, and offers future perspectives on overcoming these barriers.
{"title":"Current challenges and future directions of ATMPs in regenerative medicine","authors":"Fatemeh Abbasi Kakroodi , Elaheh Khodadoust , Marzieh Alizadeh , Reyhaneh Sadat Hayaei Tehrani , Pedram Asadi Sarabi , Mohammad Rahmanian , Massoud Vosough","doi":"10.1016/j.reth.2025.06.017","DOIUrl":"10.1016/j.reth.2025.06.017","url":null,"abstract":"<div><div>Advanced therapy medicinal products (ATMPs) represent a groundbreaking category of medications that utilize biological-based products to treat or replace damaged organs. It offers potential solutions for complex diseases through gene therapy, somatic cell therapy, tissue engineering, and combined therapies. Although ATMPs have offered significant improvement for a variety of severe illnesses, their progressive development is faced with numerous challenges. Some of these challenges are current complexities in their manufacturing, such as scaling up, scaling out, product efficacy, packaging, storage, stability, and logistic concerns. Other challenges include manufacturing, efficacy, and scaling up of ATMPs, as well as establishing Good Manufacturing Practice (GMP)-compliant processes that align with product specifications derived from non-clinical studies conducted under Good Laboratory Practice (GLP). Additionally, safety concerns such as tumorigenesis are potential. Regulatory and ethical concerns, along with the need for standardization and clear clinical guidelines, are also critical obstacles. To address these challenges, novel technologies such as organoids, artificial intelligence, dynamic culture systems, and biobanking are being explored, providing new opportunities to enhance the consistency, scalability, and precision of ATMP production. Development in artificial intelligence (AI) technology helped scientists to address monitoring concerns, automation, and data management. Introducing advanced guidelines in biobanking helps researchers to overcome the storage and stability concerns. Organoid technology holds a significant promise in overcoming the challenges associated with preclinical and modeling of ATMPs by providing more accurate models for diseases, drug screening, and personalized medicine. This article reviews the current challenges in ATMP manufacturing and application, highlights the advancements in technology that are paving the way for improved therapeutic strategies, and offers future perspectives on overcoming these barriers.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 358-370"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplantation of expanded corneal endothelial cells (CECs) has been regarded as a promising approach for treating corneal diseases caused by CEC damage or dysfunction. However, an efficient method for expanding CECs remains inadequately established.
Methods
We examined whether small molecule inhibitors of large tumor suppressor kinase (LATS) promote the proliferation of CECs. We also evaluated the expression of functional markers in CECs treated with the inhibitors.
Results
We found that LATS kinase inhibitors enhance the cell density of bovine CECs ex vivo. CECs that were expanded in the presence of these inhibitors exhibited increased nuclear translocation of yes-associated protein (YAP) and upregulated expression of YAP-regulated genes. Furthermore, we observed that YAP was essential for promoting cell proliferation. Notably, the inhibitors also increased the density of primary human CECs. Expanded human CECs expressed CEC functional markers, including Na+/K+-transporting ATPase subunit alpha-1 (ATP1A1), Zonula occludens-1 (ZO-1), and N-cadherin; they showed upregulated expression of YAP-regulated genes.
Conclusions
Collectively, these findings support the development of efficient culture techniques for CEC expansion and may facilitate the advancement of therapeutic strategies for CEC-associated diseases.
{"title":"Ex vivo expansion of corneal endothelial cells enabled by small molecule inhibitors of LATS kinase","authors":"Natsuki Abe-Fukasawa , Ryuhei Hayashi , Mio Morita , Shohei Azuma , Takumi Iwawaki , Kenta Kagaya , Taito Nishino , Kohji Nishida","doi":"10.1016/j.reth.2025.08.014","DOIUrl":"10.1016/j.reth.2025.08.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Transplantation of expanded corneal endothelial cells (CECs) has been regarded as a promising approach for treating corneal diseases caused by CEC damage or dysfunction. However, an efficient method for expanding CECs remains inadequately established.</div></div><div><h3>Methods</h3><div>We examined whether small molecule inhibitors of large tumor suppressor kinase (LATS) promote the proliferation of CECs. We also evaluated the expression of functional markers in CECs treated with the inhibitors.</div></div><div><h3>Results</h3><div>We found that LATS kinase inhibitors enhance the cell density of bovine CECs <em>ex vivo</em>. CECs that were expanded in the presence of these inhibitors exhibited increased nuclear translocation of yes-associated protein (YAP) and upregulated expression of YAP-regulated genes. Furthermore, we observed that YAP was essential for promoting cell proliferation. Notably, the inhibitors also increased the density of primary human CECs. Expanded human CECs expressed CEC functional markers, including Na<sup>+</sup>/K<sup>+</sup>-transporting ATPase subunit alpha-1 (ATP1A1), Zonula occludens-1 (ZO-1), and N-cadherin; they showed upregulated expression of YAP-regulated genes.</div></div><div><h3>Conclusions</h3><div>Collectively, these findings support the development of efficient culture techniques for CEC expansion and may facilitate the advancement of therapeutic strategies for CEC-associated diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 730-739"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-05-16DOI: 10.1016/j.reth.2025.05.005
Goshi Shiota (Senior Associate Editor)
{"title":"Preface of the special issue “Mechanisms of reprogramming for cell differentiation and tissue regeneration”","authors":"Goshi Shiota (Senior Associate Editor)","doi":"10.1016/j.reth.2025.05.005","DOIUrl":"10.1016/j.reth.2025.05.005","url":null,"abstract":"","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Page 46"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell processing facilities for regenerative medicine require strict prevention of cross-contamination. However, the typically employed sealed, multi-room layout increases energy demands and capital costs due to heating, ventilation, and air-conditioning (HVAC), and restricts staff mobility. We devised a semi-open (SO) cleanroom that eliminated doors between the cell processing room (CPR) and adjoining corridor, while maintaining unidirectional airflow as a barrier. This study rigorously compared four interface variants—plain opening, wing walls, push–pull ventilation, and a conventional swing door—to verify whether operational flexibility can be achieved without compromising particle content performance at the CPR–corridor interface.
Methods
Computational fluid dynamics (CFD) simulations reproduced two connected rooms separated by a 900 × 2000-mm2 opening, supplied at 23 m3/min (35 air changes per hour) constantly. Four interfaces were evaluated: plain opening, 100–500 mm wing-wall panels, push–pull ventilation adjusted to a 0.75 ratio, and a conventional swing door. A 1-m/s cross-draft emulated personnel transit. Identical full-scale mock-ups were built; particle image velocimetry (PIV) quantified airflow vectors, and optical counters logged 0.5-μm aerosols during 5-min exit and entry. The primary endpoints were the inflow particle concentration ratio across the opening and the cumulative adjacent-room transfer proportions.
Results
CFD showed all layouts leaked ≤0.011 %, with a 1 m/s walking draft, push–pull kept inflow below 0.05 %, halving 500-mm wing-wall performance and outperforming plain openings. The PIV confirmed significant differences in airflow velocity distributions under each condition in the case of the exit. The semi-open layout without doors showed a lower proportion of vectors pointing opposite to the forward direction than the conventional layout in both the exit and entry cases. Particle counts supported this: push–pull transferred 0.013 % of particles on exit, 32.8 % on entry, giving overall migration to the adjacent room of 0.0043 %.
Conclusions
The SO cleanroom concept suppresses fluctuations in particle content at the CPR–corridor interface while eliminating physical doors, enabling flexible personnel flow and obviating extra HVAC zones. Push–pull ventilation delivered the most robust containment against walking-induced disturbances, whereas the 500-mm wing walls offered a passive, power-free alternative with moderate protection. With worst-case inter-room transfers below 0.05 %, SO designs can rationally replace conventional door-sealed rooms, substantially reducing energy and construction costs in regenerative medicine manufacturing.
{"title":"Optimized personnel flow with minimal contamination: development and validation of an air-barrier cleanroom for cell products processing","authors":"Mitsuru Mizuno , Hideaki Tani , Kaori Nomura , Daijiro Sone , Kentaro Amano , Gen Tominaga , Yuki Chiba , Ichiro Sekiya","doi":"10.1016/j.reth.2025.09.001","DOIUrl":"10.1016/j.reth.2025.09.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Cell processing facilities for regenerative medicine require strict prevention of cross-contamination. However, the typically employed sealed, multi-room layout increases energy demands and capital costs due to heating, ventilation, and air-conditioning (HVAC), and restricts staff mobility. We devised a semi-open (SO) cleanroom that eliminated doors between the cell processing room (CPR) and adjoining corridor, while maintaining unidirectional airflow as a barrier. This study rigorously compared four interface variants—plain opening, wing walls, push–pull ventilation, and a conventional swing door—to verify whether operational flexibility can be achieved without compromising particle content performance at the CPR–corridor interface.</div></div><div><h3>Methods</h3><div>Computational fluid dynamics (CFD) simulations reproduced two connected rooms separated by a 900 × 2000-mm<sup>2</sup> opening, supplied at 23 m<sup>3</sup>/min (35 air changes per hour) constantly. Four interfaces were evaluated: plain opening, 100–500 mm wing-wall panels, push–pull ventilation adjusted to a 0.75 ratio, and a conventional swing door. A 1-m/s cross-draft emulated personnel transit. Identical full-scale mock-ups were built; particle image velocimetry (PIV) quantified airflow vectors, and optical counters logged 0.5-μm aerosols during 5-min exit and entry. The primary endpoints were the inflow particle concentration ratio across the opening and the cumulative adjacent-room transfer proportions.</div></div><div><h3>Results</h3><div>CFD showed all layouts leaked ≤0.011 %, with a 1 m/s walking draft, push–pull kept inflow below 0.05 %, halving 500-mm wing-wall performance and outperforming plain openings. The PIV confirmed significant differences in airflow velocity distributions under each condition in the case of the exit. The semi-open layout without doors showed a lower proportion of vectors pointing opposite to the forward direction than the conventional layout in both the exit and entry cases. Particle counts supported this: push–pull transferred 0.013 % of particles on exit, 32.8 % on entry, giving overall migration to the adjacent room of 0.0043 %.</div></div><div><h3>Conclusions</h3><div>The SO cleanroom concept suppresses fluctuations in particle content at the CPR–corridor interface while eliminating physical doors, enabling flexible personnel flow and obviating extra HVAC zones. Push–pull ventilation delivered the most robust containment against walking-induced disturbances, whereas the 500-mm wing walls offered a passive, power-free alternative with moderate protection. With worst-case inter-room transfers below 0.05 %, SO designs can rationally replace conventional door-sealed rooms, substantially reducing energy and construction costs in regenerative medicine manufacturing.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 760-768"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The visceral pleura is a thin, serous membrane that closely covers the surface of the lung. The pleura is injured or ruptured, causing air to accumulate in the thoracic cavity and the lung to collapse. Increased pleural pressure due to lung air leaks (LALs) from the lung can have serious effects. LALs are frequently observed due to pleural injury caused by lung resection. Postoperative LALs prolongs hospital stay and has a significant impact on patients' postoperative quality of life. Based on the above background, we developed and reported the effectiveness of dermal fibroblast sheet (DFS) as a bio-artificial pleura for closing LALs caused by intraoperative pleural injury in humans for the first time in a clinical study. There are no mid-term reports of bio-artificial pleura created using tissue engineering. In this study, we report the safety of bio-artificial pleural transplantation using cultured autologous DFS for pleural injury in two cases.
Previous study and case presentation
Two of the five patients who met the criteria and underwent LAL closure using a bio-artificial pleura between May 2016 and March 2018 were followed up mid-term. Although the criteria included a 6-month monitoring period after LAL closure, these two patients continued to visit our hospital beyond the monitoring period for treatment of other comorbid conditions. Case 1. A male in his 40s who was receiving long-term steroid therapy for Takayasu's disease and underwent thoracoscopic lung wedge resection for a benign lung tumor in the left anteromedial basal segment. During surgery, the minor LALs from the resection margins with an automatic stapler were closed with a bio-artificial pleura, specifically, a total of three DFSs. During the patient's 51-month follow-up, no LAL recurrence, tumor development, infiltration, and fibrogenesis were observed. Case 2. A female patient in her 70s had bullae associated with combined pulmonary fibrosis and emphysema (CPFE). Thoracoscopic bullectomy of the left lower lobe was performed, and the major LALs were closed intraoperatively with a bio-artificial pleura consisting of a total of eight DFSs. She was readmitted for contralateral pneumonia 2 months after surgery. During a follow-up period of 82 months, no LAL recurrence and tumor development was observed in the operated left lung. However, chest CT revealed slowly progressing CPFE lesions.
Conclusions
This report of two cases demonstrated the mid-term safety of bio-artificial pleural transplantation using cultured autologous DFS for pleural injury.
{"title":"Mid-term outcomes of a bio-artificial pleura composed of autologous dermal fibroblasts used to close intraoperative pulmonary air leaks caused by intraoperative pleural injury: A case report","authors":"Masato Kanzaki , Ryo Takagi , Shota Mitsuboshi , Tamami Isaka , Masayuki Yamato","doi":"10.1016/j.reth.2025.06.001","DOIUrl":"10.1016/j.reth.2025.06.001","url":null,"abstract":"<div><h3>Introduction</h3><div>The visceral pleura is a thin, serous membrane that closely covers the surface of the lung. The pleura is injured or ruptured, causing air to accumulate in the thoracic cavity and the lung to collapse. Increased pleural pressure due to lung air leaks (LALs) from the lung can have serious effects. LALs are frequently observed due to pleural injury caused by lung resection. Postoperative LALs prolongs hospital stay and has a significant impact on patients' postoperative quality of life. Based on the above background, we developed and reported the effectiveness of dermal fibroblast sheet (DFS) as a bio-artificial pleura for closing LALs caused by intraoperative pleural injury in humans for the first time in a clinical study. There are no mid-term reports of bio-artificial pleura created using tissue engineering. In this study, we report the safety of bio-artificial pleural transplantation using cultured autologous DFS for pleural injury in two cases.</div></div><div><h3>Previous study and case presentation</h3><div>Two of the five patients who met the criteria and underwent LAL closure using a bio-artificial pleura between May 2016 and March 2018 were followed up mid-term. Although the criteria included a 6-month monitoring period after LAL closure, these two patients continued to visit our hospital beyond the monitoring period for treatment of other comorbid conditions. Case 1. A male in his 40s who was receiving long-term steroid therapy for Takayasu's disease and underwent thoracoscopic lung wedge resection for a benign lung tumor in the left anteromedial basal segment. During surgery, the minor LALs from the resection margins with an automatic stapler were closed with a bio-artificial pleura, specifically, a total of three DFSs. During the patient's 51-month follow-up, no LAL recurrence, tumor development, infiltration, and fibrogenesis were observed. Case 2. A female patient in her 70s had bullae associated with combined pulmonary fibrosis and emphysema (CPFE). Thoracoscopic bullectomy of the left lower lobe was performed, and the major LALs were closed intraoperatively with a bio-artificial pleura consisting of a total of eight DFSs. She was readmitted for contralateral pneumonia 2 months after surgery. During a follow-up period of 82 months, no LAL recurrence and tumor development was observed in the operated left lung. However, chest CT revealed slowly progressing CPFE lesions.</div></div><div><h3>Conclusions</h3><div>This report of two cases demonstrated the mid-term safety of bio-artificial pleural transplantation using cultured autologous DFS for pleural injury.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 234-240"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-07-29DOI: 10.1016/j.reth.2025.07.007
Siwen Zhang , Xudong Zhang , Haochen Zhang , Shengqing Zhang , Zichen Liu , Shanshan Wu , Yimeng Lu , Chao Han , Jichun Tan
Introduction
Platelet-rich plasma (PRP) is a plasma product that concentrates platelets from whole blood and used widely in regenerative medicine. This study aimed to evaluate the evolution, development trend, and research highlights of research status of PRP in regenerative medicine.
Methods
Publications related to PRP were retrieved from the Science Citation Index Expanded (SCIE) database of the Web of Science (WoS) in February 2024. The impact factor (IF) was used to evaluate and compare the contributions of different countries. Then, the top 10 countries, top 10 productive journals, top 10 WoS categories, and top 10 most cited articles were listed. The data was processed, and the relative contributions of the top 10 productive countries in each year were presented in a line chart and a heatmap. VOSviewer software and heatmap were used to investigate the holistic trend of research highlights according to the change trends of keywords.
Results
A total of 9,577 publications were retrieved from SCIE database. The USA topped the list with 2,311 papers, followed by China (1,583 papers), the UK (525 papers), and Spain (512 papers). The studies of PRP in regenerative medicine have increasing trend globally. The USA had the most total citation and took the leading position for relative contributions, the UK ranked 1st in average citations and average IF. However, China's contribution had a dramatically increasing trend since 2015, and exceeded the USA in 2022. There were seven keywords of “Bone-related cluster”, “hyaluronic acid-related cluster”, “cartilage-related cluster”, “stomatology-related cluster”, “damage repair-related cluster”, “experiment-related cluster”, and “nerve-related cluster” generated in keyword co-occurrence analysis. Except for bone & joint diseases, novel clinical applications of PRP have been carried out, including dental and neurological practice, reproductive medicine, dermatology, gynecology, and plastic surgery, cosmetic treatments, and the improvement of non-musculoskeletal organ function.
Conclusion
To summarize, the research advancements of PRP appear to be more prominent in the United States and China. Experimental research on PRP is mostly concentrated on exploring on mechanism and signal pathway. As an effective adjuvant treatment, the clinical application of PRP has expanded from initial trauma repair to multiple systemic organ disorders. Leveraging the intersection of multiple disciplines, the development of novel PRP-based medical materials tailored to specific disease characteristics may represent a promising direction for future research.
富血小板血浆(PRP)是一种浓缩全血血小板的血浆产品,广泛用于再生医学。本研究旨在评价PRP在再生医学研究现状的演变、发展趋势和研究重点。方法从Web of Science (WoS)的SCIE数据库中检索2024年2月与PRP相关的出版物。影响因子(IF)被用来评价和比较不同国家的贡献。然后,列出了排名前10的国家、排名前10的高产期刊、排名前10的WoS类别和排名前10的被引文章。对数据进行了处理,并以折线图和热图的形式展示了每年产量最高的10个国家的相对贡献。根据关键词的变化趋势,利用VOSviewer软件和热图对研究亮点进行整体趋势调查。结果SCIE数据库共检索文献9577篇。美国以2311篇论文位居榜首,其次是中国(1583篇)、英国(525篇)、西班牙(512篇)。PRP在再生医学领域的研究在全球范围内呈增长趋势。美国的总被引次数最多,相对贡献排名第一,英国的平均被引次数和平均影响因子排名第一。但自2015年以来,中国的贡献呈急剧上升趋势,并在2022年超过了美国。关键词共现分析共生成“骨相关类”、“透明质酸相关类”、“软骨相关类”、“口腔相关类”、“损伤修复相关类”、“实验相关类”、“神经相关类”7个关键词。除了骨头&;在关节疾病方面,PRP的新临床应用已经开展,包括牙科和神经医学、生殖医学、皮肤科、妇科、整形外科、美容治疗以及非肌肉骨骼器官功能的改善。综上所述,PRP在美国和中国的研究进展较为突出。PRP的实验研究多集中在机理和信号通路的探索上。作为一种有效的辅助治疗,PRP的临床应用已经从最初的创伤修复扩展到多系统器官疾病。利用多学科交叉,开发针对特定疾病特征的新型prp医疗材料可能是未来研究的一个有希望的方向。
{"title":"A bibliometric analysis of the global status of platelet-rich plasma in regenerative medicine from 2004 to 2023","authors":"Siwen Zhang , Xudong Zhang , Haochen Zhang , Shengqing Zhang , Zichen Liu , Shanshan Wu , Yimeng Lu , Chao Han , Jichun Tan","doi":"10.1016/j.reth.2025.07.007","DOIUrl":"10.1016/j.reth.2025.07.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Platelet-rich plasma (PRP) is a plasma product that concentrates platelets from whole blood and used widely in regenerative medicine. This study aimed to evaluate the evolution, development trend, and research highlights of research status of PRP in regenerative medicine.</div></div><div><h3>Methods</h3><div>Publications related to PRP were retrieved from the Science Citation Index Expanded (SCIE) database of the Web of Science (WoS) in February 2024. The impact factor (IF) was used to evaluate and compare the contributions of different countries. Then, the top 10 countries, top 10 productive journals, top 10 WoS categories, and top 10 most cited articles were listed. The data was processed, and the relative contributions of the top 10 productive countries in each year were presented in a line chart and a heatmap. VOSviewer software and heatmap were used to investigate the holistic trend of research highlights according to the change trends of keywords.</div></div><div><h3>Results</h3><div>A total of 9,577 publications were retrieved from SCIE database. The USA topped the list with 2,311 papers, followed by China (1,583 papers), the UK (525 papers), and Spain (512 papers). The studies of PRP in regenerative medicine have increasing trend globally. The USA had the most total citation and took the leading position for relative contributions, the UK ranked 1st in average citations and average IF. However, China's contribution had a dramatically increasing trend since 2015, and exceeded the USA in 2022. There were seven keywords of “Bone-related cluster”, “hyaluronic acid-related cluster”, “cartilage-related cluster”, “stomatology-related cluster”, “damage repair-related cluster”, “experiment-related cluster”, and “nerve-related cluster” generated in keyword co-occurrence analysis. Except for bone & joint diseases, novel clinical applications of PRP have been carried out, including dental and neurological practice, reproductive medicine, dermatology, gynecology, and plastic surgery, cosmetic treatments, and the improvement of non-musculoskeletal organ function.</div></div><div><h3>Conclusion</h3><div>To summarize, the research advancements of PRP appear to be more prominent in the United States and China. Experimental research on PRP is mostly concentrated on exploring on mechanism and signal pathway. As an effective adjuvant treatment, the clinical application of PRP has expanded from initial trauma repair to multiple systemic organ disorders. Leveraging the intersection of multiple disciplines, the development of novel PRP-based medical materials tailored to specific disease characteristics may represent a promising direction for future research.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 456-464"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}