Max H P Gay, Helen Baldomero, Dominique Farge-Bancel, Pamela G Robey, Scott Rodeo, Jakob Passweg, Magdalena Müller-Gerbl, Ivan Martin
{"title":"The Survey on Cellular and Tissue-Engineered Therapies in Europe in 2016 and 2017.","authors":"Max H P Gay, Helen Baldomero, Dominique Farge-Bancel, Pamela G Robey, Scott Rodeo, Jakob Passweg, Magdalena Müller-Gerbl, Ivan Martin","doi":"10.1089/ten.TEA.2020.0092","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0092","url":null,"abstract":"<p><p>This report describes activity in Europe for the years 2016 and 2017 in the area of cellular and tissue-engineered therapies, excluding hematopoietic stem cell treatments for the reconstitution of hematopoiesis. It is the eighth of its kind and is supported by five established scientific organizations. In 2016 and 2017, a combined 234 teams from 29 countries responded to the cellular and engineered tissue therapy survey; 227 teams reported treating 8236 patients in these 2 years. Indications were categorized in <i>hematology/oncology</i> (40%; predominantly prevention or treatment of graft vs. host disease and hematopoietic graft enhancement), <i>musculoskeletal/rheumatological</i> disorders (29%), <i>cardiovascular</i> disorders (6%), <i>neurological</i> disorders (4%), <i>gastrointestinal</i> disorders (<1%), as well as <i>miscellaneous</i> disorders (20%), which were not assigned to the previous indications. The predominantly used cells were autologous (61%). The majority of autologous cells were used to treat <i>musculoskeletal/rheumatological</i> (44%) disorders, whereas allogeneic cells were mainly used for <i>hematology/oncology</i> (78%). The reported cell types were mesenchymal stem/stromal cells (MSCs) (56%), hematopoietic cells (21%), keratinocytes (7%), chondrocytes (6%) dermal fibroblasts (4%), dendritic cells (2%), and other cell types (4%). Cells were expanded <i>in vitro</i> in 62% of the treatments, sorted in 11% of the cases, and rarely transduced (2%). The processing of cells was outsourced to external facilities in 30% of the cases. Cells were delivered predominantly intravenously or intra-arterially [47%], as suspension [36%], or using a membrane/scaffold (16%). The data are compared with those from previous years to identify trends in a rapidly evolving field. In this edition, the report includes a critical discussion of data collected in the space of orthopedics and the use of MSCs.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"336-350"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38165392","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}
Sophie Winkler, Hilkea Mutschall, Jonas Biggemann, Tobias Fey, Peter Greil, Carolin Körner, Volker Weisbach, Andrea Meyer-Lindenberg, Andreas Arkudas, Raymund E Horch, Dominik Steiner
{"title":"Human Umbilical Vein Endothelial Cell Support Bone Formation of Adipose-Derived Stem Cell-Loaded and 3D-Printed Osteogenic Matrices in the Arteriovenous Loop Model.","authors":"Sophie Winkler, Hilkea Mutschall, Jonas Biggemann, Tobias Fey, Peter Greil, Carolin Körner, Volker Weisbach, Andrea Meyer-Lindenberg, Andreas Arkudas, Raymund E Horch, Dominik Steiner","doi":"10.1089/ten.TEA.2020.0087","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0087","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> For the regeneration of large volume tissue defects, the interaction between angiogenesis and osteogenesis is a crucial prerequisite. The surgically induced angiogenesis by means of an arteriovenous loop (AVL), is a powerful methodology to enhance vascularization of osteogenic matrices. Moreover, the AVL increases oxygen and nutrition supply, thereby supporting cell survival as well as tissue formation. Adipose-derived stem cells (ADSCs) are interesting cell sources because of their simple isolation, expansion, and their osteogenic potential. This study targets to investigate the coimplantation of human ADSCs after osteogenic differentiation and human umbilical vein endothelial cells (HUVECs), embedded in a vascularized osteogenic matrix of hydroxyapatite (HAp) ceramic for bone tissue engineering. <b><i>Materials and Methods:</i></b> An osteogenic matrix consisting of HAp granules and fibrin has been vascularized by means of an AVL. Trials in experimental groups of four settings were performed. Control experiments without any cells (A) and three cell-loaded groups using HUVECs (B), ADSCs (C), as well as the combination of ADSCs and HUVECs (D) were performed. The scaffolds were implanted in a porous titanium chamber, fixed subcutaneously in the hind leg of immunodeficient Rowett Nude rats and explanted after 6 weeks. <b><i>Results:</i></b> In all groups, the osteogenic matrix was strongly vascularized. Moreover, remodeling processes and bone formation in the cell-containing groups with more bone in the coimplantation group were proved successful. <b><i>Conclusion:</i></b> Vascularization and bone formation of osteogenic matrices consisting of ADSCs and HUVECs in the rat AVL model could be demonstrated successfully for the first time. Hence, the coimplantation of differentiated ADSCs with HUVECs may therefore be considered as a promising approach for bone tissue engineering.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"413-423"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38204021","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}
Mohamed Habib, Devante A Horne, Khaled Hussein, Dezba Coughlin, Erik I Waldorff, Nianli Zhang, James T Ryaby, Jeffrey C Lotz
{"title":"Magnetic Nanoparticles Synergize with Pulsed Magnetic Fields to Stimulate Osteogenesis <i>In Vitro</i>.","authors":"Mohamed Habib, Devante A Horne, Khaled Hussein, Dezba Coughlin, Erik I Waldorff, Nianli Zhang, James T Ryaby, Jeffrey C Lotz","doi":"10.1089/ten.TEA.2020.0102","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0102","url":null,"abstract":"<p><p>Delayed bone healing is a major challenge in orthopedic clinical practice, highlighting a need for technologies to overcome ineffective cell growth and osteogenic differentiation. The objective of this study was to investigate the synergistic effects of the PhysioStim (PEMF) signal with iron-ion doped tri-calcium phosphate bone substitute on human mesenchymal stem cell (hMSC) osteogenesis <i>in vitro</i>. Intrinsically magnetic nano-bone substitutes (MNBS) were developed with single particles on the order of 100 nm, saturation magnetization of 0.425 emu/g, and remanent magnetization of 0.013 emu/g. MNBS were added to hMSC culture and cell viability, alkaline phosphatase (ALP) activity, mineralization, and osteogenic gene expression in the presence and absence of PEMF were quantified for up to 10 days. MNBS attached to the surface of and were internalized by hMSCs when cultured together for 4 days and had no impact on cell viability with PEMF exposure for up to 7 days. Although total ALP activity was significantly increased with PEMF treatment alone, with a peak at day 5, PEMF combined with MNBS significantly increased ALP activity, with a peak at day 3, compared with all other groups (<i>p</i> < 0.01). The shift can be explained by significantly increased extracellular ALP activity beginning at day 2 (<i>p</i> < 0.01). PEMF combined with MNBS demonstrated continuously increasing mineralization overtime, with significantly greater Alizarin Red S concentration compared with all other groups at day 7 (<i>p</i> < 0.01). Increases in ALP activity and mineral content were in agreement with osteogenic gene expression that demonstrated peak <i>ALP</i> gene expression at day 1, and upregulated <i>BMP-2</i>, <i>BGLAP</i>, and <i>SPP1</i> gene expression at day 7 (<i>p</i> < 0.05). The results of this study demonstrate the synergistic effects of PEMF and MNBS on osteogenesis and suggest that PEMF and MNBS may provide a method for accelerated bone healing.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"402-412"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38222494","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}
Nikhil B Nayakawde, Ketaki Methe, Goditha U Premaratne, Debashish Banerjee, Michael Olausson
{"title":"Combined Use of Detergents and Ultrasonication for Generation of an Acellular Pig Larynx.","authors":"Nikhil B Nayakawde, Ketaki Methe, Goditha U Premaratne, Debashish Banerjee, Michael Olausson","doi":"10.1089/ten.TEA.2020.0054","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0054","url":null,"abstract":"<p><p>The larynx is a fairly complex organ comprised of different muscles, cartilages, mucosal membrane, and nerves. Larynx cancer is generally the most common type of head and neck cancer. Treatment options are limited in patients with total or partial laryngectomy. Tissue-engineered organs have shown to be a promising alternative treatment for patients with laryngectomy. In this report we present an alternative and simple procedure to construct a whole pig larynx scaffold consisting of complete acellular structures of integrated muscle and cartilage. Larynges were decellularized (DC) using perfusion-agitation with detergents coupled with ultrasonication. DC larynges were then characterized to investigate the extracellular matrix (ECM) proteins, residual DNA, angiogenic growth factors, and morphological and ultrastructural changes to ECM fibers. After 17 decellularization cycles, no cells were observed in all areas of the larynx as confirmed by hematoxylin and eosin and DAPI (4',6-diamidino-2-phenylindole) staining. However, DC structures of dense thyroid and cricoid cartilage showed remnants of cells. All structures of DC larynges (epiglottis [<i>p</i> < 0.0001], muscle [<i>p</i> < 0.0001], trachea [<i>p</i> = 0.0045], and esophagus [<i>p</i> = 0.0008]) showed DNA <50 ng/mg compared with native larynx. Immunohistochemistry, Masson's trichrome staining, and Luminex analyses showed preservation of important ECM proteins and angiogenic growth factors in DC larynges. Compared with other growth factors, mostly retained growth factors in DC epiglottis, thyroid muscle, and trachea include granulocyte colony-stimulating factor, Leptin, fibroblast growth factor-1, Follistatin, hepatocyte growth factor, and vascular endothelial growth factor-A. Scanning electron microscopy and transmission electron microscopy analysis confirmed the structural arrangements of ECM fibers in larynges to be well preserved after DC. Our findings suggest that larynges can be effectively DC using detergent ultrasonication. ECM proteins and angiogenic growth factors appear to be better preserved using this method when compared with the native structures of larynges. This alternative DC method could be helpful in building scaffolds from dense tissue structures such as cartilage, tendon, larynx, or trachea for future <i>in vitro</i> recellularization studies or <i>in vivo</i> implantation studies in the clinic.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"362-371"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38204016","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}
Yuanjia Zhu, Akshara D Thakore, Justin M Farry, Jinsuh Jung, Shreya Anilkumar, Hanjay Wang, Annabel M Imbrie-Moore, Matthew H Park, Nicholas A Tran, Yi-Ping Joseph Woo
{"title":"Collagen-Supplemented Incubation Rapidly Augments Mechanical Property of Fibroblast Cell Sheets.","authors":"Yuanjia Zhu, Akshara D Thakore, Justin M Farry, Jinsuh Jung, Shreya Anilkumar, Hanjay Wang, Annabel M Imbrie-Moore, Matthew H Park, Nicholas A Tran, Yi-Ping Joseph Woo","doi":"10.1089/ten.TEA.2020.0128","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0128","url":null,"abstract":"<p><p>Cell sheet technology using UpCell™ (Thermo Fisher Scientific, Roskilde, Denmark) plates is a modern tool that enables the rapid creation of single-layered cells without using extracellular matrix (ECM) enzymatic digestion. Although this technique has the advantage of maintaining a sheet of cells without needing artificial scaffolds, these cell sheets remain extremely fragile. Collagen, the most abundant ECM component, is an attractive candidate for modulating tissue mechanical properties given its tunable property. In this study, we demonstrated rapid mechanical property augmentation of human dermal fibroblast cell sheets after incubation with bovine type I collagen for 24 h on UpCell plates. We showed that treatment with collagen resulted in increased collagen I incorporation within the cell sheet without affecting cell morphology, cell type, or cell sheet quality. Atomic force microscopy measurements for controls, and cell sheets that received 50 and 100 μg/mL collagen I treatments revealed an average Young's modulus of their respective intercellular regions: 6.6 ± 1.0, 14.4 ± 6.6, and 19.8 ± 3.8 kPa during the loading condition, and 10.3 ± 4.7, 11.7 ± 2.2, and 18.1 ± 3.4 kPa during the unloading condition. This methodology of rapid mechanical property augmentation of a cell sheet has a potential impact on cell sheet technology by improving the ease of construct manipulation, enabling new translational tissue engineering applications.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"328-335"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38184287","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}
Maria Eleni Manthou, Dilyana Gencheva, Nektarios Sinis, Svenja Rink, Theodora Papamitsou, Diana Abdulla, Habib Bendella, Levent Sarikcioglu, Doychin N Angelov
{"title":"Facial Nerve Repair by Muscle-Vein Conduit in Rats: Functional Recovery and Muscle Reinnervation.","authors":"Maria Eleni Manthou, Dilyana Gencheva, Nektarios Sinis, Svenja Rink, Theodora Papamitsou, Diana Abdulla, Habib Bendella, Levent Sarikcioglu, Doychin N Angelov","doi":"10.1089/ten.TEA.2020.0045","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0045","url":null,"abstract":"<p><p>The facial nerve is the most frequently damaged nerve in head and neck traumata. Repair of interrupted nerves is generally reinforced by fine microsurgical techniques; nevertheless, regaining all functions is the exception rather than the rule. The so-called \"postparalytic syndrome,\" which includes synkinesia and altered blink reflexes, follows nerve injury. The purpose of this study was to examine if nerve-gap repair using an autologous vein filled with skeletal muscle would improve axonal regeneration, reduce neuromuscular junction polyinnervation, and improve the recovery of whisking in rats with transected and sutured right buccal branches of the facial nerve. Vibrissal motor performance was studied with the use of a video motion analysis. Immunofluorescence was used to visualize and analyze target muscle reinnervation. The results taken together indicate a positive effect of muscle-vein-combined conduit (MVCC) on the improvement of the whisking function after reparation of the facial nerve in rats. The findings support the recent suggestion that a venal graft with implantation of a trophic source, such as autologous denervated skeletal muscle, may promote the monoinnervation degree and ameliorate coordinated function of the corresponding muscles.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"351-361"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38208937","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}
Isis Côrtes, Renata A M Matsui, Mayra S Azevedo, Anderson Beatrici, Kleber L A Souza, Guilaume Launay, Frédéric Delolme, José M Granjeiro, Catherine Moali, Leandra S Baptista
{"title":"A Scaffold- and Serum-Free Method to Mimic Human Stable Cartilage Validated by Secretome.","authors":"Isis Côrtes, Renata A M Matsui, Mayra S Azevedo, Anderson Beatrici, Kleber L A Souza, Guilaume Launay, Frédéric Delolme, José M Granjeiro, Catherine Moali, Leandra S Baptista","doi":"10.1089/ten.TEA.2018.0311","DOIUrl":"https://doi.org/10.1089/ten.TEA.2018.0311","url":null,"abstract":"<p><p>A stabilized cartilage construct without signs of hypertrophy in chondrocytes is still a challenge. Suspensions of adipose stem/stromal cells (ASCs) and cartilage progenitor cells (CPCs) were seeded into micromolded nonadhesive hydrogel to produce spheroids (scaffold- and serum-free method) characterized by size, immunohistochemistry, fusion, and biomechanical properties. After cell dissociation, they were characterized for mesenchymal cell surface markers, cell viability, and quantitative real-time polymerase chain reaction. Both targeted and nontargeted (shotgun mass spectrometry) analyses were conducted on the culture supernatants. Induced ASC spheroids (ø = 350 μm) showed high cell viability and CD73 downregulation contrasting to CD90. The transforming growth factor (TGF)-β3/TGF-β1 ratio and <i>SOX9</i> increased (<i>p</i> < 0.05), whereas interleukin (IL)-6, IL-8, <i>RUNX2</i>, and <i>ALPL</i> decreased. Induced ASC spheroids were able to completely fuse and showed a higher force required to compression at day 14 (<i>p</i> < 0.0001). Strong collagen type II <i>in situ</i> was associated with gradual decrease of collagen type X and a lower <i>COLXA1</i> gene expression at day 14 compared with day 7 (<i>p</i> = 0.0352). The comparison of the secretome content of induced and non-induced ASCs and CPCs identified 138 proteins directly relevant to chondrogenesis of 704 proteins in total. Although collagen X was absent, thrombospondin-1 (TSP-1), described as antiangiogenic and antihypertrophic, and cartilage oligomeric matrix protein (COMP), a biomarker of chondrogenesis, were upregulated in induced ASC spheroids. Our scaffold- and serum-free method mimics stable cartilage acting as a tool for biomarker discovery and for regenerative medicine protocols. Impact Statement Promising adult stem cell sources for cartilage regeneration include adipose stem/stromal cells (ASCs) from subcutaneous adipose tissue. Our main objective was the development of a reproducible and easy-to-handle scaffold- and serum-free method to obtain stable cartilage from induced ASC spheroids. In addition to targeted protein profiling and biomechanical analysis, we provide the first characterization of the secretome composition for ASC spheroids, providing a useful tool to monitor <i>in vitro</i> chondrogenesis and a noninvasive quality control of tissue-engineered constructs. Furthermore, our secretome analysis revealed a potential novel biomarker-thrombospondin-1 (TSP-1), known by its antiangiogenic properties and recently described as an antihypertrophic protein.</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"311-327"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2018.0311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36931860","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}
Juliana A Passipieri, Jack Dienes, Joseph Frank, Joshua Glazier, Andrew Portell, Kaushik P Venkatesh, Jacqueline M Bliley, Damian Grybowski, Benjamin K Schilling, Kacey G Marra, George J Christ
{"title":"Adipose Stem Cells Enhance Nerve Regeneration and Muscle Function in a Peroneal Nerve Ablation Model.","authors":"Juliana A Passipieri, Jack Dienes, Joseph Frank, Joshua Glazier, Andrew Portell, Kaushik P Venkatesh, Jacqueline M Bliley, Damian Grybowski, Benjamin K Schilling, Kacey G Marra, George J Christ","doi":"10.1089/ten.TEA.2018.0244","DOIUrl":"https://doi.org/10.1089/ten.TEA.2018.0244","url":null,"abstract":"<p><p>Severe peripheral nerve injuries have devastating consequences on the quality of life in affected patients, and they represent a significant unmet medical need. Destruction of nerve fibers results in denervation of targeted muscles, which, subsequently, undergo progressive atrophy and loss of function. Timely restoration of neural innervation to muscle fibers is crucial to the preservation of muscle homeostasis and function. The goal of this study was to evaluate the impact of addition of adipose stem cells (ASCs) to polycaprolactone (PCL) nerve conduit guides on peripheral nerve repair and functional muscle recovery in the setting of a critical size nerve defect. To this end, peripheral nerve injury was created by surgically ablating 6 mm of the common peroneal nerve in a rat model. A PCL nerve guide, filled with ASCs and/or poloxamer hydrogel, was sutured to the nerve ends. Negative and positive controls included nerve ablation only (no repair), and reversed polarity autograft nerve implant, respectively. Tibialis anterior (TA) muscle function was assessed at 4, 8, and 12 weeks postinjury, and nerve and muscle tissue was retrieved at the 12-week terminal time point. Inclusion of ASCs in the PCL nerve guide elicited statistically significant time-dependent increases in functional recovery (contraction) after denervation; ∼25% higher than observed in acellular (poloxamer-filled) implants and indistinguishable from autograft implants, respectively, at 12 weeks postinjury (<i>p</i> < 0.05, <i>n</i> = 7-8 in each group). Analysis of single muscle fiber cross-sectional area (CSA) revealed that ASC-based treatment of nerve injury provided a better recapitulation of the overall distribution of muscle fiber CSAs observed in the contralateral TA muscle of uninjured limbs. In addition, the presence of ASCs was associated with improved features of re-innervation distal to the defect, with respect to neurofilament and S100 (Schwann cell marker) expression. In conclusion, these initial studies indicate significant benefits of inclusion of ASCs to the rate and magnitude of both peripheral nerve regeneration and functional recovery of muscle contraction, to levels equivalent to autograft implantation. These findings have important implications to improved nerve repair, and they provide input for future work directed to restoration of nerve and muscle function after polytraumatic injury. Impact Statement This works explores the application of adipose stem cells (ASCs) for peripheral nerve regeneration in a rat model. Herein, we demonstrate that the addition of ASCs in poloxamer-filled PCL nerve guide conduits impacts nerve regeneration and recovery of muscle function, to levels equivalent to autograft implantation, which is considered to be the current gold standard treatment. This study builds on the importance of a timely restoration of innervation to muscle fibers for preservation of muscle homeostasis, and it will provide input for future work aiming ","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"297-310"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2018.0244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36950302","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}
Sohtaro Kajiyama, Yuri Nagashima, Taichiro Funatsu, Takuma Suzuki, Meri Fukaya, Yuji Matsushima, Takatoshi Nagano, John E Davies, Kazuhiro Gomi
{"title":"Effects of Conditioned Medium from Bone Marrow Cells on Human Umbilical Cord Perivascular Cells.","authors":"Sohtaro Kajiyama, Yuri Nagashima, Taichiro Funatsu, Takuma Suzuki, Meri Fukaya, Yuji Matsushima, Takatoshi Nagano, John E Davies, Kazuhiro Gomi","doi":"10.1089/ten.TEA.2020.0025","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0025","url":null,"abstract":"<p><p>Mesenchymal cells derived from human umbilical cord tissue are attracting increasing attention as a source for cell therapy. However, for applying the same in tissue engineering, it has been shown that the differentiation capacity of mesenchymal stromal cells (MSCs) is influenced by the tissue from which the cells are harvested. Thus, to explore the possibility of increasing the osteogenic capacity of MSCs derived from the perivascular tissue of the human umbilical cord (human umbilical cord perivascular cells, HUCPVCs), we cultured these cells using conditioned medium (CM) derived from cultures of human bone marrow-derived mesenchymal stromal cells (hBMMSCs). However, hBM-CM contains a wide variety of growth factors, the amounts and ratios of which are considered to vary with the cell culture stage. Thus, we aimed to evaluate the effects of hBM-CM derived from different stages of hBMMSC culture on the osteogenic capacity of HUCPVCs. The stages of hBMMSC culture were defined as follows: Stage 1 (mitogenic stage) represented the period from the start of hBMMSC culture to 70% cell confluence; Stage 2 (confluent stage) represented the period from 70% confluence to the initiation of calcified nodule formation; and Stage 3 (calcification stage) represented the period following the initiation of calcified nodule formation. An analysis of growth factors contained in the CM obtained at each stage by enzyme-linked immunosorbent assay showed that insulin-like growth factor 1 (IGF-1) was significantly elevated at Stage 2, whereas vascular endothelial growth factor (VEGF) was significantly elevated at Stage 3. HUCPVCs were cultured using the CM from each of the stages for 1, 2, or 3 weeks. <i>RUNX2</i> expression was the most upregulated at week 1 and then downregulated in all the groups. The expression of collagen 1 was significantly elevated in Stage 2 HUCs at week 3. Alkaline phosphatase (ALP) activity, ALP, and alizarin staining were higher in Stage 2 HUCs and Stage 3 HUCs. The calcium content was the highest in Stage 2 HUCs. The calcium content of HUCPVC obtained by the method used in this study was six times higher than that reported in the previous study. Collectively, our results show that the CM obtained at Stage 2 was most effective in driving the osteogenic differentiation of HUCPVCs. Impact Statement Mesenchymal stromal cells (MSCs) derived from the perivascular tissue of umbilical cords are promising candidates for regenerative medicine. Because these are able to be differentiated into bone cells, cartilage cells, and adipocytes. The number of MSCs in perivascular tissue (HUCPVCs) is ∼1/300 but the number of HUCPVCs that differentiates into osteogenic cells is quite low. In order to promote osteogenic differentiation of HUCPVCs, we cultured HUCPVCs using conditioned medium collected from human bone marrow-derived mesenchymal stromal cells. Our study suggests that the use of conditioned medium can be effective on inducing osteogenic differe","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"382-389"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38197807","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":"Collagen Membrane for Guided Bone Regeneration in Dental and Orthopedic Applications.","authors":"Brent Allan, Rui Ruan, Euphemie Landao-Bassonga, Nicholas Gillman, Tao Wang, Junjie Gao, Yonghua Ruan, Yuan Xu, Clair Lee, Mithran Goonewardene, Minghao Zheng","doi":"10.1089/ten.TEA.2020.0140","DOIUrl":"https://doi.org/10.1089/ten.TEA.2020.0140","url":null,"abstract":"<p><p>Treatment of cortical bone defects is a clinical challenge. Guided bone regeneration (GBR), commonly used in oral and maxillofacial dental surgery, may show promise for orthopedic applications in repair of cortical bone defects. However, a limitation in the use of GBR for cortical bone defects is the lack of an ideal scaffold that provides sufficient mechanical support to bridge the cortical bone with minimal interference in the repair process. We have developed a new collagen membrane, CelGro™, for use in GBR. We report the material characterization of CelGro and evaluate the performance of CelGro in translational preclinical and clinical studies. The results show CelGro has a bilayer structure of different fiber alignment and is composed almost exclusively of type I collagen. CelGro was found to be completely acellular and free from xenoantigen, α-gal (galactose-alpha-1,3-galactose). In the preclinical study of a rabbit cortical bone defect model, CelGro demonstrated enhanced bone-remodeling activity and cortical bone healing. Microcomputed tomography evaluation showed early bony bridging over the defect area 30 days postoperatively, and nearly complete restoration of mature cortical bone at the bone defect site 60 days postoperatively. Histological analysis 60 days after surgery further confirmed that CelGro enables bridging of the cortical bone defect by induction of newly formed cortical bone. Compared to a commercially available collagen membrane, Bio-Gide<sup>®</sup>, CelGro showed much better cortical alignment and reduced porosity at the defect interface. As selection of orthopedic patients with cortical bone defects is complex, we conducted a clinical study evaluating the performance of CelGro in guided bone regeneration around dental implants. CelGro was used in GBR procedures in a total of 16 implants placed in 10 participants. Cone-beam computed tomography images show significantly increased bone formation both horizontally and vertically, which provides sufficient support to stabilize implants within 4 months. Together, the findings of our study demonstrate that CelGro is an ideal membrane for GBR not only in oral and maxillofacial reconstructive surgery but also in orthopedic applications (Clinical Trial ID ACTRN12615000027516).</p>","PeriodicalId":23133,"journal":{"name":"Tissue Engineering Part A","volume":" ","pages":"372-381"},"PeriodicalIF":4.1,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/ten.TEA.2020.0140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38217109","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}