{"title":"Expansion of Chondrocytes for Cartilage Tissue Engineering: A Review of Chondrocyte Dedifferentiation and Redifferentiation as a Function of Growth in Expansion Culture","authors":"J. Kisiday","doi":"10.20900/rmf20200002","DOIUrl":"https://doi.org/10.20900/rmf20200002","url":null,"abstract":"Culture-expansion is a common step in the use of autologous chondrocytes for cartilage tissue engineering. Chondrocytes dedifferentiate in monolayer expansion culture, and conditions that are sufficient to induce redifferentiation change as a function of cumulative growth. The objective of this review was to characterize the relationship between expansion and redifferentiation, from which requirements to induce redifferentiation were identified for selected approaches to cartilage tissue engineering. While chondrocytes dedifferentiate rapidly in expansion culture, transferring the cells to a three-dimensional scaffold is sufficient to induce redifferentiation for up to ~6 population doublings (PDs). Redifferentiation is possible beyond 6 PDs, although exposure to chondrogenic cytokines is needed. These data indicate that dedifferentiation with expansion for treating focal defects (~6 PDs) can be reversed with transfer to a scaffold, while joint resurfacing (~10 PDs) is anticipated to require exposure to chondrogenic cytokines. During expansion, growth factor supplementation can accelerate proliferation and improve redifferentiation. However, redifferentiation may require chondrogenic cytokines, and should be considered for approaches that involve expansion beyond the limit for spontaneous redifferentiation.","PeriodicalId":93226,"journal":{"name":"Regenerative medicine frontiers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43412645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design of Hydroxyapatite-Based Multifunctional Nanoparticles for Cell Labelling and Cell Growth Inhibition","authors":"T. Kataoka, Kota Shiba, M. Tagaya","doi":"10.20900/rmf20200001","DOIUrl":"https://doi.org/10.20900/rmf20200001","url":null,"abstract":"There has been an increasing demand for the development of cell-labeling nanomaterials that safely label and visualize a specific type of cells for diagnosis and inspection in vivo and in vitro. In order to design such \u0000cell-labeling nanomaterials, the properties of efficient visible light luminescence and effective interactions with cells have to be realized using a biocompatible nanomaterial. From this viewpoint, we summarize and overview the current situation on cell-labeling technologies. Among various functional nanomaterials, we focus on hydroxyapatite nanoparticles and their photofunctionalization based on the properly designed inorganic-organic hybrid structure such as hydroxyapatite/ \u0000organic europium (III) complex. Also, the immobilization technique of a specific binding molecule to the solid surface is introduced to demonstrate the selective uptake into cancer cells. Moreover, an example of the growth inhibitory drug molecules for cancer cells are described, focusing on the cytostatic inhibition of citric acid and the potential use of hydroxyapatite/citric acid hybrids. Finally, we mention our future perspectives on the theranostic nanoparticles with fluorescence and therapeutic properties that are achieved through the hydroxyapatite-organic hybrid interfacial interactions.","PeriodicalId":93226,"journal":{"name":"Regenerative medicine frontiers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45290827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Ribeiro, S. Pina, R. F. Canadas, A. Morais, C. Vilela, S. Vieira, I. Cengiz, R. Reis, J. Oliveira
{"title":"In Vivo Performance of Hierarchical HRP-Crosslinked Silk Fibroin/β-TCP Scaffolds for Osteochondral Tissue Regeneration","authors":"V. Ribeiro, S. Pina, R. F. Canadas, A. Morais, C. Vilela, S. Vieira, I. Cengiz, R. Reis, J. Oliveira","doi":"10.20900/rmf20190007","DOIUrl":"https://doi.org/10.20900/rmf20190007","url":null,"abstract":"Background: Osteochondral defects (OCD) can affect the articular cartilage and subchondral bone tissues, which requires superior therapies for the simultaneous and full restoration of such structurally and biologically different tissues. \u0000Methods: Tissue engineered OC grafts were prepared using a horseradish peroxidase (HRP) approach to crosslink silk fibroin (HRP-SF) as the articular cartilage-like layer and an underlying HRP-SF/ZnSrTCP subchondral bone-like layer (HRP-SF/dTCP), through salt-leaching/freeze-drying methodologies. In vivo OC regeneration was assessed by implantating the hierarchical scaffolds in rabbit critical size OC defects, during 8 weeks. A comparative analysis was performed using hierarchical OC grafts made of pure β-TCP (HRP-SF/TCP). \u0000Results: The hierarchical scaffolds showed good integration into the host tissue and no signs of acute inflammatory reaction, after 8 weeks of implantation. The histological analyses revealed positive collagen type II and glycosaminoglycans’ formation in the articular cartilage-like layer. New bone ingrowth’s and blood vessels infiltration were detected in the subchondral bone-like layers. \u0000Conclusions: The proposed hierarchical scaffolds presented an adequate in vivo response with cartilage tissue regeneration and calcified tissue formation specially promoted by the ionic incorporation into the subchondral bone layer, confirming the hierarchical structures as suitable for OCD regeneration.","PeriodicalId":93226,"journal":{"name":"Regenerative medicine frontiers","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42992288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Bragança, Leonardo Mendes-Silva, João A. Lopes, Sofia M. Calado
{"title":"CITED Proteins in the Heart of Pluripotent Cells and in Heart’s Full Potential","authors":"J. Bragança, Leonardo Mendes-Silva, João A. Lopes, Sofia M. Calado","doi":"10.20900/RMF20190005","DOIUrl":"https://doi.org/10.20900/RMF20190005","url":null,"abstract":"The CITED family of transcriptional modulators plays multiple roles in the development of vertebrates. These proteins are characterized by the conservation of a carboxy-terminal domain which defines this family and has a high affinity for the transcriptional co-activators CBP/p300. In humans, mutations in some CITED genes or deregulation of their expression are associated with developmental anomalies. In particular, CITED2 dysfunction has been associated with congenital heart disease. Although most studies have reported the critical function of CITED proteins during development, there is increasing evidence supporting an important role for these proteins in physiological functions of adult organisms and pathologies such as cardiomyopathies and cancer. In addition, recent studies have pointed out the involvement of CITED proteins in embryonic and adult stem cells self-renewal, and cell fate decisions. Here, we present an overview of the CITED transcriptional modulators, their protein interactors and gene networks, with an emphasis on their importance in pluripotent stem cells and cardiogenesis.","PeriodicalId":93226,"journal":{"name":"Regenerative medicine frontiers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44175368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sadi Loai, Benjamin R. Kingston, Zongjie Wang, David Philpott, Mingyang Tao, H. Cheng
{"title":"Clinical Perspectives on 3D Bioprinting Paradigms for Regenerative Medicine","authors":"Sadi Loai, Benjamin R. Kingston, Zongjie Wang, David Philpott, Mingyang Tao, H. Cheng","doi":"10.20900/RMF20190004","DOIUrl":"https://doi.org/10.20900/RMF20190004","url":null,"abstract":"Three-dimensional (3D) bioprinting is an emerging manufacturing technology that layers living cells and biocompatible natural or synthetic materials to build complex, functional living tissue with the requisite 3D geometries. This technology holds tremendous promise across a plethora of applications as diverse as regenerative medicine, pathophysiological studies, and drug testing. Despite some success demonstrated in early attempts to recreate complex tissue structures, however, the field of bioprinting is very much in its infancy. There are a variety of challenges to building viable, functional, and lasting 3D structures, not the least of which is translation from a research to a clinical setting. In this review, the current translational status of 3D bioprinting is assessed for several major tissue types in the body (skin, bone/cartilage, cardiovascular, central/peripheral nervous systems, skeletal muscle, kidney, and liver), recent breakthroughs and current challenges are highlighted, and future prospects for this exciting research field are discussed. We begin with an overview of the technology itself, followed by a detailed discussion of the current approaches relevant for bioprinting different tissues for regenerative medicine.","PeriodicalId":93226,"journal":{"name":"Regenerative medicine frontiers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44191275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James R Day, Anu David, Catherine Long, Grace G Bushnell, Teresa K Woodruff, Lonnie D Shea, Ariella Shikanov
{"title":"Immuno-Isolating Dual Poly(ethylene glycol) Capsule Prevents Cancer Cells from Spreading Following Mouse Ovarian Tissue Auto-Transplantation.","authors":"James R Day, Anu David, Catherine Long, Grace G Bushnell, Teresa K Woodruff, Lonnie D Shea, Ariella Shikanov","doi":"10.20900/rmf20190006","DOIUrl":"https://doi.org/10.20900/rmf20190006","url":null,"abstract":"<p><p>For female cancer survivors, premature ovarian insufficiency (POI) is a common complication of anticancer treatments. Ovarian tissue cryopreservation before treatment, followed by auto-transplantation after remission is a promising option to restore fertility and ovarian endocrine function. However, auto-transplantation is associated with the risk of re-introducing malignant cells harbored in the stroma of the ovarian autograft. To mitigate this risk, we investigated in this pilot study whether an immuno-isolating dual-layered poly(ethylene glycol)(PEG) capsule can retain cancer cells, while supporting folliculogenesis. The dual PEG capsule loaded with 1000 4T1 cancer cells retained 100% of the encapsulated cells <i>in vitro</i> for 21 days of culture. However, a greater cell load of 10,000 cells/capsule led to capsule failure and cells' release. To assess the ability of the capsule to retain cancer cells, prevent metastasis, and support folliculogenesis <i>in vivo</i> we co-encapsulated cancer cells with ovarian tissue in the dual PEG capsule and implanted subcutaneously in mice. Control mice implanted with 2000 non-encapsulated cancer cells had tumors formed within 14 days and metastasis to the lungs. In contrast, no tumor mass formation or metastasis to the lungs was observed in mice with the same number of cancer cells encapsulated in the capsule. Our findings suggest that the immuno-isolating capsule may prevent the escape of the malignant cells potentially harbored in ovarian allografts and, in the future, improve the safety of ovarian tissue auto-transplantation in female cancer survivors.</p>","PeriodicalId":93226,"journal":{"name":"Regenerative medicine frontiers","volume":"2019 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38885319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew J Osmond, Rachel R. Mizenko, Melissa D. Krebs
{"title":"Rapidly Curing Chitosan Calcium Phosphate Composites as Dental Pulp Capping Agents","authors":"Matthew J Osmond, Rachel R. Mizenko, Melissa D. Krebs","doi":"10.20900/RMF20190002","DOIUrl":"https://doi.org/10.20900/RMF20190002","url":null,"abstract":"Background: Dental caries are the most prevalent yet preventable disease in both children and adults. Current treatments cannot adequately restore tooth function while concurrently supporting the regeneration of dentin tissue. The materials presented here were designed to create a rapid curing, mechanically stable and biocompatible pulp capping agent. Methods: In this study, a rapidly curing dental composite was formed using carboxymethyl-chitosan, hydroxyapatite whiskers, and a diglycidyl ether. Properties of the composites that were measured include gelation, mechanical properties, and surface characteristics. Human dental pulp stem cells were cultured on the composites to determine cytocompatibility, proliferation, and differentiation potential. Results: All composite components were verified using XRD and ATR-FTIR. The compressive modulus was determined to be greater than 600 kPa, swelling less than 2%, and degradation less than 10%. Composites supported the growth of cells for 3 weeks. qPCR was used to measure the pre-odontoblastic marker, RUNX2. The expression of osteocalcin was measured with confocal microscopy, which showed the differentiation to odontoblastic cells. Conclusions: These materials meet the initial goals for a regenerative pulp capping agent. Further investigation could lead to the next generation of pulp capping and dental filling materials.","PeriodicalId":93226,"journal":{"name":"Regenerative medicine frontiers","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45223774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}