Haruki Nishimura, Yoichi Murata, Michael T. Mullen, Kohei Yamaura, Jacob Singer, Charles Huard, Dane R. G. Lind, William S. Hambright, Chelsea S. Bahney, Marc J. Philippon, Johnny Huard
{"title":"Combination Therapy of Losartan and Fisetin Reduces Senescence and Enhances Osteogenesis in Human Bone Marrow–Derived Mesenchymal Stem Cells","authors":"Haruki Nishimura, Yoichi Murata, Michael T. Mullen, Kohei Yamaura, Jacob Singer, Charles Huard, Dane R. G. Lind, William S. Hambright, Chelsea S. Bahney, Marc J. Philippon, Johnny Huard","doi":"10.1155/term/9187855","DOIUrl":"https://doi.org/10.1155/term/9187855","url":null,"abstract":"<div>\u0000 <p>Bone marrow–derived mesenchymal stem cells (BM-MSCs) are well established for their osteogenic potential but are prone to senescence with aging or in vitro expansion. Drug treatments that reduce cellular senescence may enhance the regenerative capacity of BM-MSCs. This study investigates the effects of losartan and fisetin, both separately and in combination, on cellular senescence and osteogenesis. Human BM-MSCs were exposed to low and high concentrations of each drug for 24 h. Our findings showed that high-dose losartan exhibited cytotoxicity, focusing subsequent analyses on the low doses. Both low-dose losartan and fisetin effectively mitigated cellular senescence, with combined treatment showing synergistic effects in reducing senescence markers. From these initial findings, subsequent experiments utilized low doses of both compounds to evaluate their effect on differentiation capacity. Our multimodal approach, incorporating flow cytometry, senescence-associated heterochromatin foci (SAHF) immunohistochemistry, senescence-associated secretory phenotype (SASP) quantification, and differentiation potential assays, revealed that the combination of 23.6 μM of losartan and 50 μM of fisetin was optimal for reducing cellular senescence and enhancing osteogenesis in BM-MSCs. These results support potential therapeutic strategies to counteract age-related declines in bone health and improve healing. By targeting cellular senescence while promoting osteogenesis, losartan and fisetin offer promising avenues for future research aimed at enhancing the regenerative capacity of BM-MSCs in the context of musculoskeletal regenerative medicine.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2025 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/term/9187855","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of Tissue Engineering and Regenerative Medicine
{"title":"RETRACTION: Changes in Immunological Parameters in Patients Treated Using Direct and Indirect Restorations of the Hard Tissues of the Anterior Teeth in Combination With an Antioxidant","authors":"Journal of Tissue Engineering and Regenerative Medicine","doi":"10.1155/term/9815150","DOIUrl":"https://doi.org/10.1155/term/9815150","url":null,"abstract":"<p>RETRACTION: I. R. Kumhyr, V. P. Levko, and Z. R. Ozhogan, “Changes in Immunological Parameters in Patients Treated Using Direct and Indirect Restorations of the Hard Tissues of the Anterior Teeth in Combination With an Antioxidant,” <i>Journal of Tissue Engineering and Regenerative Medicine</i> 14 (2020): 1001–1005, https://doi.org/10.1002/term.3054.</p><p>The above article, published online on 29 April 2020 in Wiley Online Library (https://wileyonlinelibrary.com), has been retracted by agreement between the Chief Editor, Catherine K. Kuo, and John Wiley & Sons Ltd. UK. The retraction has been agreed following concerns raised by a third party regarding the peer review process. Further investigation by the publisher has found manipulation of the peer review process. The authors did not respond to requests for an explanation. As a result, the conclusions reported in the article are not considered reliable.</p>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2025 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/term/9815150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Lee Jenkins, Sadhana Venkataraman, Aya Saleh, Sarah Calve, Behnam Pourdeyhimi, Dianne Little
{"title":"Application of Tendon-Derived Matrix and Carbodiimide Crosslinking Matures the Engineered Tendon-Like Proteome on Meltblown Scaffolds","authors":"Thomas Lee Jenkins, Sadhana Venkataraman, Aya Saleh, Sarah Calve, Behnam Pourdeyhimi, Dianne Little","doi":"10.1155/term/2184723","DOIUrl":"https://doi.org/10.1155/term/2184723","url":null,"abstract":"<div>\u0000 <p><b>Background:</b> Tendon injuries are increasingly common and heal by fibrosis rather than scar-less regeneration. Tissue engineering seeks to improve repair using synthetic polymer scaffolds with biomimetic factors to enhance the regenerative potential.</p>\u0000 <p><b>Methods:</b> In this study, we compared three groups, namely, poly(lactic acid) (PLA) meltblown scaffolds, PLA meltblown scaffolds coated with tendon-derived matrix (TDM), and PLA meltblown scaffolds with carbodiimide crosslinked TDM (2.5:1:1 EDC:NHS:COOH ratio) (EDC-TDM) and determined their potential for engineered tendon development. We cultured human adipose stem cells (hASCs) for 28 days on meltblown scaffolds (<i>n</i> = 4–6/group) and measured tensile mechanical function, matrix synthesis, and matrix composition using biochemical assays and proteomics.</p>\u0000 <p><b>Results:</b> Coating PLA meltblown scaffolds with TDM improved yield stretch and stress at 28 days compared with PLA. Matrix synthesis rates for TDM or EDC-TDM were similar to PLA. Proteomic analysis revealed that hASCs produced a collagen-rich extracellular matrix, with many tendon-related matrix proteins. Coating scaffolds with TDM led to an increase in collagen type I whereas EDC-TDM scaffolds had an increase in glycoproteins and ECM regulators compared with other groups, consistent with increased maturity of the newly deposited matrix.</p>\u0000 <p><b>Conclusions:</b> TDM coating and crosslinking of meltblown scaffolds demonstrated matricellular benefits for the proteome of engineered tendon development but provided fewer clear benefits toward mechanical, biochemical, and rate of matrix accumulation than expected, and that previous work with electrospun scaffolds would suggest. However, electrospun scaffolds have different fiber structure and microarchitecture than meltblown, suggesting that further consideration of these differences and refinement of TDM application methods to meltblown scaffolds is required.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2025 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/term/2184723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jyrki Heinämäki, Oleh Koshovyi, Iryna Botsula, Alina Shpychak, Hung Quoc Vo, Hoai Thi Nguyen, Ain Raal
{"title":"Plant-Origin Compounds and Materials for Advancing Bone Tissue Engineering and 3D Bioprinting: Traditional Medicine Aspects and Current Perspectives","authors":"Jyrki Heinämäki, Oleh Koshovyi, Iryna Botsula, Alina Shpychak, Hung Quoc Vo, Hoai Thi Nguyen, Ain Raal","doi":"10.1155/term/2812191","DOIUrl":"https://doi.org/10.1155/term/2812191","url":null,"abstract":"<div>\u0000 <p>Bone defects are becoming a true challenge in global health care due to the aging population and higher prevalence of musculoskeletal disorders. The interest in using plant-origin compounds and plant-derived biomaterials in bone tissue engineering (BTE) has been increased due to their availability (abundance), safety, biocompatibility, biodegradability, and low cost. Plant-origin compounds have supportive effects on bone tissue healing, and cell-laden plant-derived biomaterials can be applied in formulating bioinks for three-dimensional (3D) bioprinting to facilitate the preparation of native bone tissue–mimicking structures and customized bone scaffolds. Such plant-derived materials also have the capacity to improve cell viability and support osteoconductive and osteoinductive properties of a bone construct. In this article, we review the ethnomedical aspects related to the use of medicinal plants and plant-origin bioactive compounds in bone healing and the recent developments in the 3D bioprinting of bone constructs with plant-derived biomaterials for advancing BTE. The commonly used 3D-bioprinting techniques, the properties of plant-origin compounds and biomaterials (for bone 3D bioprinting), and the selective examples of bone scaffolds fabricated using plant-derived biomaterials are discussed with a special reference set on applicability, performance, advantages, limitations, and challenges. Plant-origin compounds, biomaterials, and biomimetic 3D-bioprinted constructs could be the basis for a next-generation BTE.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2025 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/term/2812191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Challenges and Advances in Peripheral Nerve Tissue Engineering Critical Factors Affecting Nerve Regeneration","authors":"Massoumeh Jabbari Fakhr, Fatemeh Kavakebian, Shima Ababzadeh, Alireza Rezapour","doi":"10.1155/2024/8868411","DOIUrl":"https://doi.org/10.1155/2024/8868411","url":null,"abstract":"<div>\u0000 <p>Peripheral neuropathy is painful and can cause a considerable decline in quality of life. Surgery and autograft are the current approaches and clinical standards for restoring function after nerve damage. However, they usually result in unacceptable clinical results, so we need modern peripheral nerve defect treatment approaches. Tissue engineering techniques have been developed as a promising approach, but there are some considerations for translational application. Clinical application of novel tissue engineering methods is related to combining the appropriate cell and scaffold type to introduce safe and efficient bioscaffolds. Efficient nerve regeneration occurs by mimicking the extracellular matrix and combining topographical, biochemical, mechanical, and conductive signs via different cells, biomolecules, and polymers. In brief, ideal engineered biomaterial scaffolds will have to cover all characteristics of nerve tissue, such as nerve number, myelin, and axon thickness. Nerve regeneration has a highly sensitive response to its surrounding microenvironment. For designing a suitable construct, matching the regenerative potential of the autograft as the golden standard is essential. This review article examines the newest advancements in peripheral nerve tissue engineering. Specifically, the discussion will focus on incorporating innovative cues, biological modification, biomaterials, techniques, and concepts in this area of research.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8868411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dina Gadalla, Maeve Kennedy, Jamie Ganem, Mustafa Suppah, Alessandra Schmitt, David G. Lott
{"title":"Polycaprolactone Fiber and Laminin and Collagen IV Protein Incorporation in Implants Enhances Wound Healing in a Novel Mouse Skin Splint Model","authors":"Dina Gadalla, Maeve Kennedy, Jamie Ganem, Mustafa Suppah, Alessandra Schmitt, David G. Lott","doi":"10.1155/2024/2515383","DOIUrl":"https://doi.org/10.1155/2024/2515383","url":null,"abstract":"<div>\u0000 <p>Wound healing is an intricate process involving multiple cells and distinct phases, presenting challenges for comprehensive investigations. Currently available treatments for wounds have limited capacity to fully restore tissue and often require significant investments of time in the form of repetitive dressing changes and/or reapplications. This article presents a novel study that aims to enhance wound healing by developing biomaterial scaffolds using Medpor®, a porous polyethylene implant, as a model scaffold. The study incorporates electrospun poly(e-caprolactone) (PCL) fibers and a protein mixture (PM) containing collagen IV and laminin onto the Medpor® scaffolds. To evaluate the impact of these implants on wound healing, a unique splinted wound model in mice is employed. The wounds were evaluated for closure, inflammation, collagen deposition, angiogenesis, epithelialization, and proliferation. The results show that wounds treated with Medpor® + PCL + PM implants demonstrate accelerated closure rates, improved epithelialization, and enhanced angiogenesis compared to other implant groups. However, there were no significant differences observed in collagen deposition and inflammatory response among the implant groups. This study provides valuable insights into the potential benefits of incorporating PCL fibers and a PM onto scaffolds to enhance wound healing. Furthermore, the developed splinted wound model with integrated implants offers a promising platform for future studies on implant efficacy and the advancement of innovative wound healing strategies.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/2515383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Herpesvirus-Entry Mediator Inhibits the NF-κB Pathway Activated by IL-17 and Fosters the Osteogenic Differentiation of Allogeneic Mesenchymal Stem Cells","authors":"Zhigang Rong, Yuhang Xi, Chengmin Zhang, Wei Dai, Hao Xue, Fei Luo, Jianzhong Xu, Fei Dai","doi":"10.1155/2024/8146991","DOIUrl":"https://doi.org/10.1155/2024/8146991","url":null,"abstract":"<div>\u0000 <p>The challenge in developing tissue-engineered bones (TEBs) for clinical applications lies in the constraints associated with the source and availability of autologous mesenchymal stem cells (MSCs) derived from the bone marrow, which creates a bottleneck. While allogeneic MSCs have shown promise in TEB applications, their ability to promote bone growth is notably diminished because of the inflammatory reaction at the transplant site and the inherent immune response triggered by allogeneic MSCs. Hence, there is a pressing need to develop methods that enhance the osteogenic differentiation of allogeneic MSCs during transplantation. Previous studies have found that IL-17 is a key proinflammatory factor in initiating inflammation and cascade amplification in the early stages of an inflammatory response, and proinflammatory cytokines such as TNF-<i>α</i> and IL-17 can inhibit the osteogenic differentiation of MSCs in an immune environment. In this study, MSCs expressing HVEM were successfully constructed by viral transfection and further reconfirmed that IL-17 can inhibit the in vivo and in vitro osteogenesis of allogeneic MSCs through in vitro experiments and mouse calvarial bone defect (diameter about 3 mm) model, while MSCs that express herpesvirus-entry mediator (HVEM) exhibit the capacity to suppress immune responses and sustain strong osteogenic potential. We further pointed out that the mechanism by which HVEM promotes the osteogenesis of allogeneic MSCs is related to its inhibition of the I<i>κ</i>B kinase (IKK)-NF-<i>κ</i>B signaling pathway activated by IL-17 in the immune environment, which can significantly inhibit the ubiquitination and degradation of <i>β</i>-catenin in MSCs induced by the IKK-NF-<i>κ</i>B pathway, upregulate the expression of <i>β</i>-catenin, and promote bone formation. Hence, this research provides an initial connection between the Wnt/<i>β</i>-catenin signaling pathway and the IKK-NF-<i>κ</i>B pathway during allogeneic MSC transplantation, offering new avenues for investigation and establishing a theoretical foundation for the potential use of HVEM-expressing MSCs in clinical treatments for bone defects.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8146991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thirapurasundari Vikranth, Tina Dale, Nicholas R. Forsyth
{"title":"Decellularisation and Characterisation of Porcine Pleura as Bioscaffolds in Tissue Engineering","authors":"Thirapurasundari Vikranth, Tina Dale, Nicholas R. Forsyth","doi":"10.1155/2024/9940673","DOIUrl":"https://doi.org/10.1155/2024/9940673","url":null,"abstract":"<div>\u0000 <p>Persistent air leaks caused by thoracic surgery, physical trauma, or spontaneous pneumothoraces are a cause of patient morbidity with need for extended chest tube durations and surgical interventions. Current treatment measures involve mechanical closure of air leaks in the compromised pleura. Organ and membrane decellularisation offers a broad range of biomimetic scaffolds of allogeneic and xenogeneic origins, exhibiting innate tissue-specific characteristics. We explored a physicochemical method for decellularising porcine pleural membranes (PPM) as potential tissue-engineered surrogates for lung tissue repair. Decellularised PPM (dPPM) was characterised with histology, quantitative assays, mechanical testing, and sterility evaluation. Cytotoxicity and recellularisation assays assessed biocompatibility of decellularised PPM (dPPM). Haematoxylin and Eosin (H&E) staining showed an evident reduction in stained nuclei in the dPPM, confirmed with nuclear staining and analysis ( <sup>∗∗∗∗</sup><i>p</i> < 0.0001). Sulphated glycosaminoglycans (sGAG) and collagen histology demonstrated minimal disruption to the gross structural assembly of core extracellular matrix (ECM) in dPPM. Confocal imaging demonstrated realignment of ECM fibres in dPPM against native control. Quantitative analysis defined a significant change in the angular distribution ( <sup>∗∗∗∗</sup><i>p</i> < 0.0001) and coherence ( <sup>∗∗∗</sup><i>p</i> < 0.001) of fibre orientations in dPPM versus native ECM. DNA quantification indicated ≥85% reduction in native nuclear dsDNA in dPPM ( <sup>∗∗</sup><i>p</i> < 0.01). Collagen and sGAG quantification indicated reductions of both ( <sup>∗∗</sup><i>p</i> < 0.01). dPPM displayed increased membrane thickness ( <sup>∗∗∗</sup><i>p</i> < 0.001). However, Young’s modulus (459.67 ± 10.36 kPa) and ultimate tensile strength (4036.22 ± 155.1 kPa) of dPPM were comparable with those of native controls at (465.82 ± 10.51 kPa) and (3912.9 ± 247.42 kPa), respectively. <i>In vitro</i> cytotoxicity and scaffold biocompatibility assays demonstrated robust human mesothelial cell line (MeT-5A) attachment and viability. DNA quantification in reseeded dPPM with MeT-5A cells exhibited significant increase in DNA content at day 7 ( <sup>∗∗</sup><i>p</i> < 0.01) and day 15 ( <sup>∗∗∗∗</sup><i>p</i> < 0.0001) against unseeded dPPM. Here, we define a decellularisation protocol for porcine pleura that represents a step forward in their potential tissue engineering applications as bioscaffolds.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/9940673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angus Weekes, Joanna M. Wasielewska, Nigel Pinto, Jason Jenkins, Jatin Patel, Zhiyong Li, Travis J. Klein, Christoph Meinert
{"title":"Harnessing the Regenerative Potential of Fetal Mesenchymal Stem Cells and Endothelial Colony-Forming Cells in the Biofabrication of Tissue-Engineered Vascular Grafts (TEVGs)","authors":"Angus Weekes, Joanna M. Wasielewska, Nigel Pinto, Jason Jenkins, Jatin Patel, Zhiyong Li, Travis J. Klein, Christoph Meinert","doi":"10.1155/2024/8707377","DOIUrl":"https://doi.org/10.1155/2024/8707377","url":null,"abstract":"<div>\u0000 <p>Tissue engineering is a promising approach for the production of small-diameter vascular grafts; however, there are limited data directly comparing the suitability of applicable cell types for vessel biofabrication. Here, we investigated the potential of adult smooth muscle cells (SMCs), placental mesenchymal stem cells (MSCs), placental endothelial colony-forming cells (ECFCs), and a combination of MSCs and ECFCs on highly porous biocompatible poly(<i>ɛ</i>-caprolactone) (PCL) scaffolds produced via melt electrowriting (MEW) for the biofabrication of tissue-engineered vascular grafts (TEVGs). Cellular attachment, proliferation, and deposition of essential extracellular matrix (ECM) components were analysed <i>in vitro</i> over four weeks. TEVGs cultured with MSCs accumulated the highest levels of collagenous components within a dense ECM, while SMCs and the coculture were more sparsely populated, ascertained via histological and immunofluorescence imaging, and biochemical assessment. Scanning electron microscopy (SEM) enabled visualisation of morphological differences in cell attachment and growth, with MSCs and SMCs infiltrating and covering scaffolds completely within the 28-day culture period. Coverage and matrix deposition by ECFCs was limited. However, ECFCs lined the ECM formed by MSCs in coculture, visualised via immunostaining. Thus, of cells investigated, placental MSCs were identified as the preferred cell source for the fabrication of tissue-engineered constructs, exhibiting extensive population of porous polymer scaffolds and production of ECM components; with the inclusion of ECFCs for luminal endothelialisation, an encouraging outcome warranting further consideration in future studies. In combination, these findings represent a substantial step toward the development of the next generation of small-diameter vascular grafts in the management of cardiovascular disease.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8707377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chromatin Condensation Delays Senescence in Human Mesenchymal Stem Cells by Safeguarding Nuclear Damages during In Vitro Expansion","authors":"Rohit Joshi, Tejas Suryawanshi, Sourav Mukherjee, Shobha Shukla, Abhijit Majumder","doi":"10.1155/2024/1543849","DOIUrl":"10.1155/2024/1543849","url":null,"abstract":"<div>\u0000 <p>Human mesenchymal stem cells (hMSCs) are multipotent cells that differentiate into adipocytes, chondrocytes, and osteoblasts. Owing to their differentiation potential, hMSCs are among the cells most frequently used for therapeutic applications in tissue engineering and regenerative medicine. However, the number of cells obtained through isolation alone is insufficient for hMSC-based therapies and basic research, which necessitates <i>in vitro</i> expansion. Conventionally, this is often performed on rigid surfaces such as tissue culture plates (TCPs). However, during <i>in vitro</i> expansion, hMSCs lose their proliferative ability and multilineage differentiation potential, rendering them unsuitable for clinical use. Although multiple approaches have been attempted to maintain hMSC stemness during prolonged expansion, finding a suitable culture system remains an unmet need. Recently, a few research groups have shown that hMSCs maintain their stemness over long passages when cultured on soft substrates. In addition, it has been shown that hMSCs cultured on soft substrates have more condensed chromatin and lower levels of histone acetylation compared to those cultured on stiff substrates. Furthermore, it has also been shown that condensing/decondensing chromatin by deacetylation/acetylation can delay replicative senescence in hMSCs during long-term expansion on TCPs. However, the mechanism by which chromatin condensation/decondensation influences nuclear morphology and DNA damage, which are strongly related to the onset of senescence, remains unknown. To answer this question, we cultured hMSCs for long duration in the presence of epigenetic modifiers, histone acetyltransferase inhibitor (HATi), which promotes chromatin condensation by preventing histone acetylation, and histone deacetylase inhibitor (HDACi), which promotes chromatin decondensation, and investigated their effects on various nuclear markers related to senescence. We found that consistent acetylation causes severe nuclear abnormalities, whereas chromatin condensation by deacetylation helps to safeguard the nucleus from damage caused by <i>in vitro</i> expansion.</p>\u0000 </div>","PeriodicalId":202,"journal":{"name":"Journal of Tissue Engineering and Regenerative Medicine","volume":"2024 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/1543849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140992901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}