Pub Date : 2024-12-17DOI: 10.1016/j.reth.2024.12.003
Yuan-Xia Zou , Jiraporn Kantapan , Hong-Lian Wang , Jian-Chun Li , Hong-Wei Su , Jian Dai , Nathupakorn Dechsupa , Li Wang
Background
Acute kidney injury (AKI) is a life-threatening clinical syndrome with no effective treatment currently available. This study aims to investigate whether Iron-Quercetin complex (IronQ) pretreatment can enhance the therapeutic efficacy of Mesenchymal stem cells (MSCs) in AKI and explore the underlying mechanisms.
Methods
A cisplatin-induced AKI model was established in male C57BL/6 mice, followed by the intravenous administration of 1x10ˆ6 MSCs or IronQ-pretreated MSCs (MSCIronQ). Renal function, histology, and tubular cell apoptosis were analyzed three days post-treatment. In vitro, apoptosis was induced in mouse tubular epithelial cells (mTECs) using cisplatin, followed by treatment with MSCs or MSCIronQ conditioned medium (CM). Apoptosis was evaluated using TUNEL assay, RT-PCR, and western blotting. Furthermore, RNA sequencing (RNA-seq) was performed on MSCIronQ to explore the underlying mechanisms.
Results
Compared to MSC-treated AKI mice, those treated with MSCIronQ showed significantly improved renal function and histological outcomes, with reduced tubular cell apoptosis. A similar effect was observed in cisplatin-treated mTECs exposed to MSCIronQ-CM. Mechanistically, RNA-seq and subsequent validation revealed that IronQ treatment markedly upregulated the expression and secretion of hepatocyte growth factor (HGF) in MSCs. Furthermore, RNA interference or antibody-mediated neutralization of HGF effectively abolished the anti-apoptotic effects of MSCIronQ on mTECs. This mechanistic insight was reinforced by pharmacological inhibition of c-Met, the specific receptor of HGF, in both in vitro and in vivo models.
Conclusions
IronQ pretreatment enhances MSCs efficacy in AKI by promoting HGF expression and secretion, activating the HGF/c-Met pathway to suppress tubular cell apoptosis. These findings indicate that IronQ improves MSC-based therapies and offers insights into molecular mechanisms, supporting the development of better AKI treatments.
{"title":"Iron-Quercetin complex enhances mesenchymal stem cell-mediated HGF secretion and c-Met activation to ameliorate acute kidney injury through the prevention of tubular cell apoptosis","authors":"Yuan-Xia Zou , Jiraporn Kantapan , Hong-Lian Wang , Jian-Chun Li , Hong-Wei Su , Jian Dai , Nathupakorn Dechsupa , Li Wang","doi":"10.1016/j.reth.2024.12.003","DOIUrl":"10.1016/j.reth.2024.12.003","url":null,"abstract":"<div><h3>Background</h3><div>Acute kidney injury (AKI) is a life-threatening clinical syndrome with no effective treatment currently available. This study aims to investigate whether Iron-Quercetin complex (IronQ) pretreatment can enhance the therapeutic efficacy of Mesenchymal stem cells (MSCs) in AKI and explore the underlying mechanisms.</div></div><div><h3>Methods</h3><div>A cisplatin-induced AKI model was established in male C57BL/6 mice, followed by the intravenous administration of 1x10ˆ6 MSCs or IronQ-pretreated MSCs (MSC<sup>IronQ</sup>). Renal function, histology, and tubular cell apoptosis were analyzed three days post-treatment. In vitro, apoptosis was induced in mouse tubular epithelial cells (mTECs) using cisplatin, followed by treatment with MSCs or MSC<sup>IronQ</sup> conditioned medium (CM). Apoptosis was evaluated using TUNEL assay, RT-PCR, and western blotting. Furthermore, RNA sequencing (RNA-seq) was performed on MSC<sup>IronQ</sup> to explore the underlying mechanisms.</div></div><div><h3>Results</h3><div>Compared to MSC-treated AKI mice, those treated with MSC<sup>IronQ</sup> showed significantly improved renal function and histological outcomes, with reduced tubular cell apoptosis. A similar effect was observed in cisplatin-treated mTECs exposed to MSC<sup>IronQ</sup>-CM. Mechanistically, RNA-seq and subsequent validation revealed that IronQ treatment markedly upregulated the expression and secretion of hepatocyte growth factor (HGF) in MSCs. Furthermore, RNA interference or antibody-mediated neutralization of HGF effectively abolished the anti-apoptotic effects of MSC<sup>IronQ</sup> on mTECs. This mechanistic insight was reinforced by pharmacological inhibition of c-Met, the specific receptor of HGF, in both in vitro and in vivo models.</div></div><div><h3>Conclusions</h3><div>IronQ pretreatment enhances MSCs efficacy in AKI by promoting HGF expression and secretion, activating the HGF/c-Met pathway to suppress tubular cell apoptosis. These findings indicate that IronQ improves MSC-based therapies and offers insights into molecular mechanisms, supporting the development of better AKI treatments.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 169-182"},"PeriodicalIF":3.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-16DOI: 10.1016/j.reth.2024.12.001
Chaofan Wang , Yimei Du , Changpei Lu , Lingbo Bi , Yunbu Ding , Weixin Fan
Background
Secreted frizzled-related protein 1 (SFRP1) inhibits Wnt signaling and is differentially expressed in human hair dermal papilla cells (DPCs). However, the specific effect of SFRP1 on cell function remains unclear. Telomerase reverse transcriptase (TERT) representing telomerase activity was found highly active around the hair dermal papilla. TERT levels can be enhanced by activation of the Wnt pathway in cancer cells and embryonic stem cells. Whether this regulatory mechanism is still present in DPCs has not been studied so far.
Methods
In this study, DNA plasmids and siRNAs were constructed against the SFRP1 gene and transfected into DPCs cultured in vitro. We detected the viability, proliferation, and migration of DPCs by Calcein/PI fluorescence, CCK-8, trans-well, or cell scratch experiments, and the expression of potential target genes was also determined through quantitative detection of RNA and protein.
Results
The results demonstrate a significant difference in SFRP1 levels from the control group, suggesting successful transfection of the DNA plasmid and siRNA of SFRP1 into IDPCs. Also, SFRP1 regulates the cell proliferation capacity of IDPCs and reduces their migration functions. The DPCs' living activity, proliferation, and migration function exhibited a negative correlation with the level of SFRP1. SFPR1 also inhibits the protein or RNA expression of β-catenin and TERT in DPCs.
Conclusion
It was proven that in human DPCs, different levels of SFRP1 change how cells work and control Wnt/β-catenin signaling or telomerase activity. This means that blocking SFRP1 could become a new way to treat hair loss diseases in the future.
{"title":"The role of SFRP1 in human dermal papilla cell growth and its potential molecular mechanisms as a target in regenerative therapy","authors":"Chaofan Wang , Yimei Du , Changpei Lu , Lingbo Bi , Yunbu Ding , Weixin Fan","doi":"10.1016/j.reth.2024.12.001","DOIUrl":"10.1016/j.reth.2024.12.001","url":null,"abstract":"<div><h3>Background</h3><div>Secreted frizzled-related protein 1 (SFRP1) inhibits Wnt signaling and is differentially expressed in human hair dermal papilla cells (DPCs). However, the specific effect of SFRP1 on cell function remains unclear. Telomerase reverse transcriptase (TERT) representing telomerase activity was found highly active around the hair dermal papilla. TERT levels can be enhanced by activation of the Wnt pathway in cancer cells and embryonic stem cells. Whether this regulatory mechanism is still present in DPCs has not been studied so far.</div></div><div><h3>Methods</h3><div>In this study, DNA plasmids and siRNAs were constructed against the SFRP1 gene and transfected into DPCs cultured in vitro. We detected the viability, proliferation, and migration of DPCs by Calcein/PI fluorescence, CCK-8, <em>trans</em>-well, or cell scratch experiments, and the expression of potential target genes was also determined through quantitative detection of RNA and protein.</div></div><div><h3>Results</h3><div>The results demonstrate a significant difference in SFRP1 levels from the control group, suggesting successful transfection of the DNA plasmid and siRNA of SFRP1 into IDPCs. Also, SFRP1 regulates the cell proliferation capacity of IDPCs and reduces their migration functions. The DPCs' living activity, proliferation, and migration function exhibited a negative correlation with the level of SFRP1. SFPR1 also inhibits the protein or RNA expression of β-catenin and TERT in DPCs.</div></div><div><h3>Conclusion</h3><div>It was proven that in human DPCs, different levels of SFRP1 change how cells work and control Wnt/β-catenin signaling or telomerase activity. This means that blocking SFRP1 could become a new way to treat hair loss diseases in the future.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 161-168"},"PeriodicalIF":3.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The skin is a complex organ that includes various stem cell populations. Current approaches for non-healing skin defects are sometimes inadequate and many attempts have been made to regenerate skin integrity. The aim of this review is to bridge the gap between basic research and clinical application of skin integrity regeneration.
Methods
A literature search was carried out in PubMed using combinations of the keywords “skin integrity”, “tissue-engineered skin”, “bioengineered skin”, and “skin regeneration”. Articles published from 1968 to 2023 reporting evidence from in vivo and in vitro skin regeneration experiments were included.
Results
These articles showed that stem cells can be differentiated into normal skin cells, including keratinocytes, and are a significant source of skin organoids, which are useful for investigating skin biology; and that emerging direct reprogramming methods have great potential to regenerate skin from the wounded skin surface.
Conclusion
Recent advances in skin regeneration will facilitate further advancement of both basic and clinical research in skin biology.
{"title":"Bioengineering strategies for regeneration of skin integrity: A literature review","authors":"Makoto Shiraishi , Yoshihiro Sowa , Ataru Sunaga , Kenta Yamamoto , Mutsumi Okazaki","doi":"10.1016/j.reth.2024.12.006","DOIUrl":"10.1016/j.reth.2024.12.006","url":null,"abstract":"<div><h3>Objective</h3><div>The skin is a complex organ that includes various stem cell populations. Current approaches for non-healing skin defects are sometimes inadequate and many attempts have been made to regenerate skin integrity. The aim of this review is to bridge the gap between basic research and clinical application of skin integrity regeneration.</div></div><div><h3>Methods</h3><div>A literature search was carried out in PubMed using combinations of the keywords “skin integrity”, “tissue-engineered skin”, “bioengineered skin”, and “skin regeneration”. Articles published from 1968 to 2023 reporting evidence from <em>in vivo</em> and <em>in vitro</em> skin regeneration experiments were included.</div></div><div><h3>Results</h3><div>These articles showed that stem cells can be differentiated into normal skin cells, including keratinocytes, and are a significant source of skin organoids, which are useful for investigating skin biology; and that emerging direct reprogramming methods have great potential to regenerate skin from the wounded skin surface.</div></div><div><h3>Conclusion</h3><div>Recent advances in skin regeneration will facilitate further advancement of both basic and clinical research in skin biology.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 153-160"},"PeriodicalIF":3.4,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-13DOI: 10.1016/j.reth.2024.12.002
Tihui Wang , Shujing Feng , Hao Zhou , Wenhua Mao , Ruijun Bai , Yuan Xia , Jianghu Huang , Rui Zhang , Feiyue Lin
Muscle degeneration is a common issue caused by rotator cuff tear (RCT) which significantly affects prognosis. Muscle stem cells (MuSCs) play a crucial role to prevent muscle degeneration after RCT. However, the pathological changes and detailed molecular mechanism underlying the myogenesis of MuSCs after RCT remain incomplete. The current study established single-cell landscape of supraspinatus muscles and found decreased expression of PIEZO1 and impaired myogenic potential of MuSCs from RCT patients. Reduced expression of PIEZO1 impaired the myogenesis of MuSCs by inhibiting the ERK/MAPK pathways. Furthermore, selective PIEZO1 agonist Yoda1 had the potential to alleviate muscle degeneration and improve shoulder function following RCT. This study emphasized the role of PIEZO1 in the myogenesis of MuSCs and suggested that activating PIEZO1 could be a potential non-surgical treatment option to reduce muscle degeneration after RCT.
{"title":"PIEZO1 activation enhances myogenesis and mitigates muscle degeneration in rotator cuff tear","authors":"Tihui Wang , Shujing Feng , Hao Zhou , Wenhua Mao , Ruijun Bai , Yuan Xia , Jianghu Huang , Rui Zhang , Feiyue Lin","doi":"10.1016/j.reth.2024.12.002","DOIUrl":"10.1016/j.reth.2024.12.002","url":null,"abstract":"<div><div>Muscle degeneration is a common issue caused by rotator cuff tear (RCT) which significantly affects prognosis. Muscle stem cells (MuSCs) play a crucial role to prevent muscle degeneration after RCT. However, the pathological changes and detailed molecular mechanism underlying the myogenesis of MuSCs after RCT remain incomplete. The current study established single-cell landscape of supraspinatus muscles and found decreased expression of PIEZO1 and impaired myogenic potential of MuSCs from RCT patients. Reduced expression of PIEZO1 impaired the myogenesis of MuSCs by inhibiting the ERK/MAPK pathways. Furthermore, selective PIEZO1 agonist Yoda1 had the potential to alleviate muscle degeneration and improve shoulder function following RCT. This study emphasized the role of PIEZO1 in the myogenesis of MuSCs and suggested that activating PIEZO1 could be a potential non-surgical treatment option to reduce muscle degeneration after RCT.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 143-152"},"PeriodicalIF":3.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-07DOI: 10.1016/j.reth.2024.11.014
Kunbin Li , Liming Lu , Xianli Yao , Zhiyuan Wu , Pingge Sun , Xiaopeng Wen , Xiaoxing Li , Kai Wang , Xiran Yin
Spinal cord ischemia/reperfusion (IR) injury (SCII) can cause major autonomic, sensory, and motor damage and loss. The upregulation of Nrf2, a primary orchestrator of the oxidative stress response, has beneficial effects in SCII. Here, we aimed to uncover a SCII-related transcription factor that is able to elevate Nrf2 expression. Rat PC12 cells were subjected to treatment with oxygen-glucose deprivation/reoxygenation (OGD/R) to induce an in vitro neuronal IR injury model. A rat model of SCII was established by blocking the left common carotid artery and aortic arch in SD rats. Cell viability and apoptosis were assessed by the CCK-8 assay and flow cytometry, respectively. IL-1β and TNF-α levels were detected by ELISA. The oxidative stress was tested by assessing ROS and MDA contents and SOD and GSH-Px activity. The NFATC2/Nrf2 relationship was predicted by bioinformatic analysis and validated by ChIP and luciferase reporter assays. Nrf2 and NFATC2 levels were reduced in PC12 cells after OGD/R treatment. Nrf2 increase significantly attenuated OGD/R-triggered inflammation, apoptosis and oxidative stress in PC12 cells. Moreover, Nrf2 increase alleviated spinal cord pathological changes, inflammation, apoptosis and oxidative stress in rats after SCII. Mechanistically, NFATC2 could activate Nrf2 transcription and promote its expression. Nrf2 reduction exerted a counteracting impact on NFATC2's anti-inflammation, anti-apoptosis and anti-oxidative stress functions in PC12 cells under OGD/R conditions. Our study demonstrates that the NFATC2/Nrf2 cascade has a regulatory capacity in inflammation, apoptosis and oxidative stress after SCII.
{"title":"The NFATC2/Nrf2 cascade regulates spinal cord ischemia-reperfusion injury by controlling inflammation, apoptosis and oxidative stress","authors":"Kunbin Li , Liming Lu , Xianli Yao , Zhiyuan Wu , Pingge Sun , Xiaopeng Wen , Xiaoxing Li , Kai Wang , Xiran Yin","doi":"10.1016/j.reth.2024.11.014","DOIUrl":"10.1016/j.reth.2024.11.014","url":null,"abstract":"<div><div>Spinal cord ischemia/reperfusion (IR) injury (SCII) can cause major autonomic, sensory, and motor damage and loss. The upregulation of Nrf2, a primary orchestrator of the oxidative stress response, has beneficial effects in SCII. Here, we aimed to uncover a SCII-related transcription factor that is able to elevate Nrf2 expression. Rat PC12 cells were subjected to treatment with oxygen-glucose deprivation/reoxygenation (OGD/R) to induce an <em>in vitro</em> neuronal IR injury model. A rat model of SCII was established by blocking the left common carotid artery and aortic arch in SD rats. Cell viability and apoptosis were assessed by the CCK-8 assay and flow cytometry, respectively. IL-1β and TNF-α levels were detected by ELISA. The oxidative stress was tested by assessing ROS and MDA contents and SOD and GSH-Px activity. The NFATC2/Nrf2 relationship was predicted by bioinformatic analysis and validated by ChIP and luciferase reporter assays. Nrf2 and NFATC2 levels were reduced in PC12 cells after OGD/R treatment. Nrf2 increase significantly attenuated OGD/R-triggered inflammation, apoptosis and oxidative stress in PC12 cells. Moreover, Nrf2 increase alleviated spinal cord pathological changes, inflammation, apoptosis and oxidative stress in rats after SCII. Mechanistically, NFATC2 could activate Nrf2 transcription and promote its expression. Nrf2 reduction exerted a counteracting impact on NFATC2's anti-inflammation, anti-apoptosis and anti-oxidative stress functions in PC12 cells under OGD/R conditions. Our study demonstrates that the NFATC2/Nrf2 cascade has a regulatory capacity in inflammation, apoptosis and oxidative stress after SCII.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 126-133"},"PeriodicalIF":3.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tooth extraction initiates a cascade of homeostatic and structural modifications within the periodontal tissues, culminating in alveolar ridge resorption. To prevent ridge resorption following extraction and facilitate successful placement of an implant-supported prosthesis, alveolar ridge preservation was performed.
Methods
In this study, the biocompatibility of a nanocomposite consisting of self-assembling peptide nanofibers (organic phase) and tri-calcium phosphate-nano hydroxyapatite (mineral phase), was evaluated in rabbits. Subsequently, the nanocomposite was grafted onto a model of alveolar bone repair in patients.
Results
The in vivo findings revealed no significant differences in the irritation ranking score and average thickness of the reaction zone between the nanocomposite and control groups. Furthermore, there were no significant differences in the appearance of necrosis, granulation tissue, fibroplasia, neovascularization, and hemorrhage as well as in the number of neutrophils, mast cells, lymphocytes, macrophages, and giant cells between the two groups. The defect area was completely filled with newly formed bone trabeculae and cavities containing bone marrow, indicating angiogenesis, while remnants of the scaffold were observed in the deeper region of the defects, adjacent to the bone marrow, considered osteoinductive. The clinical trial findings (TRN: IR.IUMS.REC.1401.355) demonstrated robust bone regeneration after 3.5 months of socket preservation, whereas the bone in the control group experienced atrophy. The nanocomposite facilitated soft tissue healing without any signs of infection or other periodontal malfunction.
Conclusion
The application of nanotechnology has enhanced the bio-functionality of alloplastic materials, positioning this nanocomposite a promising alternative to autografts and allografts in alveolar bone repair.
{"title":"Self-assembling peptide nanofibers and nanoceramics in a model of alveolar bone repair: Insights from in vivo experiments and clinical trial","authors":"Elahe Tahmasebi , Sareh Azadi , Samira Hajisadeghi , Hamidreza Barikani , Masoud Salehi , Mahdi Shafikhani , Fateme Mozaffari , Edris Nazarpour , Arman Torabizadeh , Ahad Khoshzaban","doi":"10.1016/j.reth.2024.11.011","DOIUrl":"10.1016/j.reth.2024.11.011","url":null,"abstract":"<div><h3>Introduction</h3><div>Tooth extraction initiates a cascade of homeostatic and structural modifications within the periodontal tissues, culminating in alveolar ridge resorption. To prevent ridge resorption following extraction and facilitate successful placement of an implant-supported prosthesis, alveolar ridge preservation was performed.</div></div><div><h3>Methods</h3><div>In this study, the biocompatibility of a nanocomposite consisting of self-assembling peptide nanofibers (organic phase) and tri-calcium phosphate-nano hydroxyapatite (mineral phase), was evaluated in rabbits. Subsequently, the nanocomposite was grafted onto a model of alveolar bone repair in patients.</div></div><div><h3>Results</h3><div>The in vivo findings revealed no significant differences in the irritation ranking score and average thickness of the reaction zone between the nanocomposite and control groups. Furthermore, there were no significant differences in the appearance of necrosis, granulation tissue, fibroplasia, neovascularization, and hemorrhage as well as in the number of neutrophils, mast cells, lymphocytes, macrophages, and giant cells between the two groups. The defect area was completely filled with newly formed bone trabeculae and cavities containing bone marrow, indicating angiogenesis, while remnants of the scaffold were observed in the deeper region of the defects, adjacent to the bone marrow, considered osteoinductive. The clinical trial findings (TRN: IR.IUMS.REC.1401.355) demonstrated robust bone regeneration after 3.5 months of socket preservation, whereas the bone in the control group experienced atrophy. The nanocomposite facilitated soft tissue healing without any signs of infection or other periodontal malfunction.</div></div><div><h3>Conclusion</h3><div>The application of nanotechnology has enhanced the bio-functionality of alloplastic materials, positioning this nanocomposite a promising alternative to autografts and allografts in alveolar bone repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 134-142"},"PeriodicalIF":3.4,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-06DOI: 10.1016/j.reth.2024.11.019
Yu Zhang , Yueda Lu , Xinyue Hu , Mengxing Jiang , Zhixiu Chen , Lingkun Jin , Min Li , Chen Chen , Jianye Wang
Human umbilical cord blood mononuclear cells (hUCB-MNCs) are a population of cells derived from neonatal cord blood, encompassing various stem cells and immune cells. The unique characteristics of hUCB-MNCs endow them with distinctive multifunctionality, including the promotion of angiogenesis, acceleration of tissue repair, regulation of immune responses, neuroprotection, alleviation of inflammatory reactions, enhancement of antioxidant capacity, reduction of fibrosis processes, and inhibition of apoptosis. These diverse biological properties underscore the significant clinical therapeutic potential of hUCB-MNCs, which are widely applied in the treatment of various diseases. This review aims to summarize the underlying mechanisms responsible for the multifunctional attributes of hUCB-MNCs, elucidating their potential modes of action in disease management and providing novel theoretical insights and practical guidance for their expanded application across different disease domains. By synthesizing current research findings, this review may provide insights into the potential clinical applications of hUCB-MNCs in the fields of regenerative medicine and cell therapy.
{"title":"Functional characterization and therapeutic potential of human umbilical cord blood mononuclear cells","authors":"Yu Zhang , Yueda Lu , Xinyue Hu , Mengxing Jiang , Zhixiu Chen , Lingkun Jin , Min Li , Chen Chen , Jianye Wang","doi":"10.1016/j.reth.2024.11.019","DOIUrl":"10.1016/j.reth.2024.11.019","url":null,"abstract":"<div><div>Human umbilical cord blood mononuclear cells (hUCB-MNCs) are a population of cells derived from neonatal cord blood, encompassing various stem cells and immune cells. The unique characteristics of hUCB-MNCs endow them with distinctive multifunctionality, including the promotion of angiogenesis, acceleration of tissue repair, regulation of immune responses, neuroprotection, alleviation of inflammatory reactions, enhancement of antioxidant capacity, reduction of fibrosis processes, and inhibition of apoptosis. These diverse biological properties underscore the significant clinical therapeutic potential of hUCB-MNCs, which are widely applied in the treatment of various diseases. This review aims to summarize the underlying mechanisms responsible for the multifunctional attributes of hUCB-MNCs, elucidating their potential modes of action in disease management and providing novel theoretical insights and practical guidance for their expanded application across different disease domains. By synthesizing current research findings, this review may provide insights into the potential clinical applications of hUCB-MNCs in the fields of regenerative medicine and cell therapy.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 101-114"},"PeriodicalIF":3.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1016/j.reth.2024.11.015
Zhongyu Wu , Zhanqi Wang , Tao Chen , Dongyang Wang , Feng Zhou , Guorui Zhang , Shan Wei , Yingying Wu
Dermal white adipose tissue (dWAT), distinguished by its origin from cells within the dermis and independence from subcutaneous fat tissue, has garnered significant attention for its non-metabolic functions. Characterized by strong communication with other components of the skin, dWAT mediates the proliferation and recruitment of various cell types by releasing adipogenic and inflammatory factors. Here, we focus on the modulatory role of dWAT at different stages during wound healing, highlighting its ability to mediate the adipocyte-to-myofibroblast transition which plays a pivotal role in the physiology and pathology processes of skin fibrosis, scarring, and aging. This review highlights the regulatory potential of dWAT in modulating wound healing processes and presents it as a target for developing therapeutic strategies aimed at reducing scarring and enhancing regenerative outcomes in skin-related disorders.
{"title":"Dermal white adipose tissue: A new modulator in wound healing and regeneration","authors":"Zhongyu Wu , Zhanqi Wang , Tao Chen , Dongyang Wang , Feng Zhou , Guorui Zhang , Shan Wei , Yingying Wu","doi":"10.1016/j.reth.2024.11.015","DOIUrl":"10.1016/j.reth.2024.11.015","url":null,"abstract":"<div><div>Dermal white adipose tissue (dWAT), distinguished by its origin from cells within the dermis and independence from subcutaneous fat tissue, has garnered significant attention for its non-metabolic functions. Characterized by strong communication with other components of the skin, dWAT mediates the proliferation and recruitment of various cell types by releasing adipogenic and inflammatory factors. Here, we focus on the modulatory role of dWAT at different stages during wound healing, highlighting its ability to mediate the adipocyte-to-myofibroblast transition which plays a pivotal role in the physiology and pathology processes of skin fibrosis, scarring, and aging. This review highlights the regulatory potential of dWAT in modulating wound healing processes and presents it as a target for developing therapeutic strategies aimed at reducing scarring and enhancing regenerative outcomes in skin-related disorders.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 115-125"},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Introduction</h3><div>Cell-processing operations can potentially contaminate biosafety cabinets, which should be maintained sterile. However, unintended contamination can occur owing to the presence of viruses, mycoplasmas, and bacteria in the raw materials. Moreover, although several methods for expunging these contaminants have been proposed, an optimal method has not yet been determined. Additionally, the effectiveness of conventional methods for eliminating these contaminants remains unclear owing to their unique characteristics and potential resistances to cleaning. Therefore, this paper proposes a risk-based approach to identify appropriate cleaning methods and reduce the likelihood of cross-contamination in biosafety cabinets by these contaminants.</div></div><div><h3>Methods</h3><div>Various cleaning methods for eliminating mycoplasmas, viruses, and endotoxins from biosafety cabinets were evaluated, including ultraviolet (UV) irradiation at 200 mJ/cm<sup>2</sup> for 20 min and wiping with disinfectants such as distilled water, benzalkonium chloride (BKC), and 70 % ethanol (ETH). The effectiveness of each method was evaluated by applying the contaminants on stainless steel plates and cleaning them using each method. <em>Mycoplasma orale</em> was cultured for 2 weeks in a liquid medium after cleaning. <em>Feline calicivirus</em> (FCV) was used for evaluating the virus-cleaning effectiveness and its presence was tested using the TCID50 test, whereas endotoxins obtained from the dried extract of <em>Escherichia coli</em> were measured via endotoxin testing.</div></div><div><h3>Results</h3><div>UV irradiation and wiping with BKC inhibited the growth of mycoplasma and significant decreased their presence compared with the other cleaning methods. Notably, mycoplasma were detected after wiping all SUS304 plates with ETH, which is a widely used cleaning method. Additionally, the cleaning efficacy for virus showed that the TCID<sub>50</sub> of the wet group was 132,000 TCID<sub>50</sub>/plate, whereas those after UV irradiation or cleaning with BKC or DW were below the detection limit. Finally, UV irradiation did not significantly reduce the endotoxin production compared with that in the dry group. Additionally, wiping with ETH did not significantly reduce endotoxins compared with the dry group and their residues were higher than those detected after wiping with BKC or DW.</div></div><div><h3>Conclusions</h3><div>The changeover protocols currently employed in most cell-processing facilities may be ineffective as pathogenic or nonpathogenic materials may remain even after ETH wiping, leading to unintended cross-contamination. To the best of our knowledge, this is the first study to provide reference data of different cleaning methods for mycoplasmas, viruses, and endotoxins in cell-product manufacturing facilities, and can potentially support the development of evidence-based management strategies for ensuring safe cell-product processing.<
{"title":"Cleaning methods for biosafety cabinet to eliminate residual mycoplasmas, viruses, and endotoxins after changeover","authors":"Mitsuru Mizuno , Saeri Kimbara , Hanae Ichise , Natsumi Ishikawa , Yuto Nishihara , Miwako Nishio , Ichiro Sekiya","doi":"10.1016/j.reth.2024.11.020","DOIUrl":"10.1016/j.reth.2024.11.020","url":null,"abstract":"<div><h3>Introduction</h3><div>Cell-processing operations can potentially contaminate biosafety cabinets, which should be maintained sterile. However, unintended contamination can occur owing to the presence of viruses, mycoplasmas, and bacteria in the raw materials. Moreover, although several methods for expunging these contaminants have been proposed, an optimal method has not yet been determined. Additionally, the effectiveness of conventional methods for eliminating these contaminants remains unclear owing to their unique characteristics and potential resistances to cleaning. Therefore, this paper proposes a risk-based approach to identify appropriate cleaning methods and reduce the likelihood of cross-contamination in biosafety cabinets by these contaminants.</div></div><div><h3>Methods</h3><div>Various cleaning methods for eliminating mycoplasmas, viruses, and endotoxins from biosafety cabinets were evaluated, including ultraviolet (UV) irradiation at 200 mJ/cm<sup>2</sup> for 20 min and wiping with disinfectants such as distilled water, benzalkonium chloride (BKC), and 70 % ethanol (ETH). The effectiveness of each method was evaluated by applying the contaminants on stainless steel plates and cleaning them using each method. <em>Mycoplasma orale</em> was cultured for 2 weeks in a liquid medium after cleaning. <em>Feline calicivirus</em> (FCV) was used for evaluating the virus-cleaning effectiveness and its presence was tested using the TCID50 test, whereas endotoxins obtained from the dried extract of <em>Escherichia coli</em> were measured via endotoxin testing.</div></div><div><h3>Results</h3><div>UV irradiation and wiping with BKC inhibited the growth of mycoplasma and significant decreased their presence compared with the other cleaning methods. Notably, mycoplasma were detected after wiping all SUS304 plates with ETH, which is a widely used cleaning method. Additionally, the cleaning efficacy for virus showed that the TCID<sub>50</sub> of the wet group was 132,000 TCID<sub>50</sub>/plate, whereas those after UV irradiation or cleaning with BKC or DW were below the detection limit. Finally, UV irradiation did not significantly reduce the endotoxin production compared with that in the dry group. Additionally, wiping with ETH did not significantly reduce endotoxins compared with the dry group and their residues were higher than those detected after wiping with BKC or DW.</div></div><div><h3>Conclusions</h3><div>The changeover protocols currently employed in most cell-processing facilities may be ineffective as pathogenic or nonpathogenic materials may remain even after ETH wiping, leading to unintended cross-contamination. To the best of our knowledge, this is the first study to provide reference data of different cleaning methods for mycoplasmas, viruses, and endotoxins in cell-product manufacturing facilities, and can potentially support the development of evidence-based management strategies for ensuring safe cell-product processing.<","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 73-80"},"PeriodicalIF":3.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-02DOI: 10.1016/j.reth.2024.11.016
Mohammad Ebrahim Astaneh , Narges Fereydouni
Introduction
Chronic wounds continue to pose a significant global challenge, incurring substantial costs and necessitating extensive research in wound healing. Our previous work involved synthesizing zein nanofibers embedded with 5 %, 10 %, and 15 % nano-curcumin (Zein/nCUR 5, 10, and 15 % NFs), and examining their physicochemical and biological properties. This study aims to explore the potential of these nanofibers in macrophage (MØ) polarization and wound healing.
Methods
We assessed the survival of RAW264.7 cells cultured on Zein/nCUR 5, 10, and 15 % NFs using the MTT assay. To evaluate MØ polarization, we measured the expression of iNOS and Arg-1 genes in MØs cultured on Zein/nCUR 10 % NFs through real-time PCR. Furthermore, we examined the nanofibers' impact on pro-inflammatory cytokine expression (IL-1β, IL-6, TNF-α) in MØs via real-time PCR. The wound healing efficacy of Zein/nCUR 10 % NFs was tested on 54 male rats with full-thickness wounds, with assessments conducted on days 3, 7, and 14. Wound closure, re-epithelialization, and collagen secretion were evaluated through photographic analysis and tissue staining. Statistical analyses were performed using GraphPad Prism 6, with significance set at p < 0.05.
Results
Zein/nCUR 10 % NFs significantly enhanced the survival of RAW264.7 cells compared to other groups. They also markedly reduced iNOS expression and increased Arg-1 expression, indicating successful polarization of M1 to M2 MØs. Additionally, these nanofibers decreased the expression of IL-1β, IL-6, and TNF-α, and significantly improved wound closure, re-epithelialization, and collagen deposition compared to control and Zein groups.
Conclusions
This study demonstrates that Zein/nCUR 10 % NFs effectively polarize MØs from M1 to M2, significantly enhancing wound healing, thus offering a promising therapeutic approach for improved wound care.
{"title":"Nanocurcumin-enhanced zein nanofibers: Advancing macrophage polarization and accelerating wound healing","authors":"Mohammad Ebrahim Astaneh , Narges Fereydouni","doi":"10.1016/j.reth.2024.11.016","DOIUrl":"10.1016/j.reth.2024.11.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic wounds continue to pose a significant global challenge, incurring substantial costs and necessitating extensive research in wound healing. Our previous work involved synthesizing zein nanofibers embedded with 5 %, 10 %, and 15 % nano-curcumin (Zein/nCUR 5, 10, and 15 % NFs), and examining their physicochemical and biological properties. This study aims to explore the potential of these nanofibers in macrophage (MØ) polarization and wound healing.</div></div><div><h3>Methods</h3><div>We assessed the survival of RAW264.7 cells cultured on Zein/nCUR 5, 10, and 15 % NFs using the MTT assay. To evaluate MØ polarization, we measured the expression of iNOS and Arg-1 genes in MØs cultured on Zein/nCUR 10 % NFs through real-time PCR. Furthermore, we examined the nanofibers' impact on pro-inflammatory cytokine expression (IL-1β, IL-6, TNF-α) in MØs via real-time PCR. The wound healing efficacy of Zein/nCUR 10 % NFs was tested on 54 male rats with full-thickness wounds, with assessments conducted on days 3, 7, and 14. Wound closure, re-epithelialization, and collagen secretion were evaluated through photographic analysis and tissue staining. Statistical analyses were performed using GraphPad Prism 6, with significance set at <em>p</em> < 0.05.</div></div><div><h3>Results</h3><div>Zein/nCUR 10 % NFs significantly enhanced the survival of RAW264.7 cells compared to other groups. They also markedly reduced iNOS expression and increased Arg-1 expression, indicating successful polarization of M1 to M2 MØs. Additionally, these nanofibers decreased the expression of IL-1β, IL-6, and TNF-α, and significantly improved wound closure, re-epithelialization, and collagen deposition compared to control and Zein groups.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that Zein/nCUR 10 % NFs effectively polarize MØs from M1 to M2, significantly enhancing wound healing, thus offering a promising therapeutic approach for improved wound care.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 51-62"},"PeriodicalIF":3.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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