Cell sheet tissue engineering, by thomas fernberg and. Tissue engineering evolved from the field of biomaterials development and refers to the practice of combining scaffolds, cells, and biologically active molecules into functional tissues. Recently, cell sheet engineering has emerged as one of the most accentuated approaches of tissue engineering and cardiac tissue is the pioneering application area of cell sheets with clinical use. Although the clinical demand for bioengineered blood vessels continues to rise, current options for vascular conduits remain limited. Larouche d, paquet c, fradette j, carrier p, auger fa, germain l 2009 regeneration of skin and cornea by tissue engineering. Cell and tissue engineering centers on the application of physical and engineering principles to understand and control cell and tissue behavior. Recent progress in cell transplantation therapy to repair impaired hearts has encouraged further attempts to bioengineer threedimensional heart tissue from cultured cardiac myocytes. Cell sheet engineering is based on the sequential stacking and adhesion of confluent and organized cell monolayers from twodimensional cell culture without the need for artifical scaffolds or structural intermediates. Stem cells embryonic stem cells and adult stem cells serve as the primary instrument of tissue engineering, a technology that has garnered a great deal of attention in civil and military research for providing possible treatment of many diseases and injuries fig. Cardiac tissue engineering for replacement therapy wolframhubertus zimmermann and thomas eschenhagen institute of experimental and clinical pharmacology and toxicology, friedrichalexanderuniversity of erlangennuremberg, germany abstract. Cells, scaffolds, and molecules for myocardial tissue engineering jonathan leora, yoram amsalema, smadar cohenb aneufeld cardiac research institute, tel aviv university, sheba medical center, tel hashomer 52621, israel bdepartment of biotechnology engineering, bengurion university of the negev, beersheva, israel abstract. Heath recent advances in stem cell technology have improved the prognosis for tissue engineering. Jungvid h and kumar a 2008 skin tissue engineering for tissue repair and.
Polynisopropylacrylamidebased smart surfaces for cell. After detachment, a cardiomyocyte sheet was wrapped around a 1. The recent advancement of stem cell biology provides enormous opportunities to engineer stem cells for tissue engineering. The cell sheet technology can deliver cells to tendon and tendonbone interface to accelerate tendon healing inagaki et al. No regeneration was observed in the control without cell sheet transplantation right. To realize cardiac regeneration using human induced pluripotent stem cells hipscs, strategies for cell preparation, tissue engineering and transplantation must be. Cell sheet based tissue engineering for fabricating 3. Degradable adhesives for surgery and tissue engineering. Skin tissue engineering skin epidermis is undergoing constant rejuvenation by shedding off its surface cells while replacing them with new cells in the proliferating basal layer that differentiate and move outward into the multiple layers of terminally differentiating cells. Tissue repair and regeneration with endogenous stem cells. Prior to cell sheet tissue engineering, scaffolds were the primary successful cell based therapy to restore damaged tissue. It is likely that many tissue engineers hypothesized the idea of harvesting a sheet of cells as one, well before it was first accomplished.
May 22, 2018 although this conventional tissue engineering procedure is widely used in bone tissue regeneration, cell sheet engineering provides an alternative way. Cardiac tissue engineering based on this technology may prove useful for heart model fabrication and cardiovascular tissue repair. The application of cell sheet engineering for bone tissue. In addition to stem cell biology, tissue engineering is an essential research field for regenerative medicine. Tissueengineering strategies based on mesenchymal stem cells mscs and cell sheets have been widely used for periodontal tissue regeneration. Stem cellderived cell sheet transplantation for heart tissue. Cell sheet engineering has evolved rapidly in recent years as a new approach for cell based therapy. Premade porous scaffolds raw materials native tissues confluent cells cell sheet cell seeding lamination cell seeded scaffolds cell seeded scaffolds multiple cell sheets implantation defective tissues tissue engineering scaffolds ical chemical fibrous for example, electrospun. The integration of stem cell technology and cell sheet engineering improved the potential use of cell sheet products in regenerative medicine. Cell sheet based tissue engineering has a promising and enormous potential in myocardial tissue regenerative medicine and will cure many patients suffering from severe cardiac disease. Regenerative therapies using cell sheetbased tissue. Asu scientists boost geneediting tools to new heights in human stem cells. A challenge for tissue engineering is to identify appropriate cell sources.
Mesenchymal stem cells mscs are defined as adult native cells that have the ability to differentiate into tissues. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or. As discussed previously, elps by themselves are not particularly cell adhesive. Skin tissue engineering for tissue repair and regeneration. Tissue engineering integrates knowledge and tools from biological sciences and engineering for tissue regeneration. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or improve damaged tissues or whole organs. Mar 31, 2010 as a temporary supporter, the biodegradable gelatin hydrogel could facilitate cell sheet transfer and avoid longterm residence of foreign carriers in the body. Stem cell derived sheet engineering has been developed as the nextgeneration treatment for myocardial infarction mi and offers attractive advantages in comparison with direct stem cell transplantation and scaffold tissue engineering. Application of tissue engineering in stem cell therapy jong kyu hong1.
Course overviewclinical problems for tissue engineering solution. Threedimensional periodontal tissue regeneration using a. Application of tissue engineering in stem cell therapy. Polysaccharides as cell carriers for tissue engineering. However, it is prerequisite for bmscs to mobilize from bone marrow. Methods for harvesting cell sheets temperatureresponsive culture dishes.
We have developed cell sheet engineering in order to avoid the limitations of tissue reconstruction using biodegradable. Jan 01, 2020 conceptual illustration of tissue regeneration using cell sheet technology. The use of plateletrich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering. Transplantation of adipose tissuederived stem cell sheet to. This is a fairly new technology, originating in 1990 1. Recent investigations have indicated that these cells are critical for their trophic and immunomodulatory role in controlling endogenous cells. Jun 25, 2014 clinical studies using cell sheets have shown positive outcomes and will be translated into clinical practice in the near future. To this end, elps have been used to form cell sheet growth substrates from which they can be recovered as simply cells and their ecm. In table 3, we have provided examples of studies dealing with cell sheets for tendon tissue engineering and their outcomes.
Cell sheet a replaces damaged tissue and cells, b secrets proregenerative cytokines to stimulate hostmediated regeneration of damaged tissue and cells, and c reconstructs 3d tissue by cell sheet layering. Pdf application of the cell sheet technique in tissue. The traditional method harvests cells by trypsin digestion, which results in the loss of large numbers of cells and a reduction in cell activity. Cell sheetbased tissue engineering for fabricating 3. Tissue engineering is the use of a combination of cells, engineering, and materials methods, and suitable biochemical and physicochemical factors to improve or replace biological tissues. These techniques are classified as scaffoldbased and scaffoldfree techniques. Cartilage repair using cell sheet engineering in rat model. Specimens of human tissue engineered epithelial cell sheets harvested by reducing. While it was once categorized as a subfield of biomaterials, having grown in scope and.
Cells, scaffolds, and molecules for myocardial tissue. Cell sheet tissue engineering, by thomas fernberg and julia. Pdf cell sheet tissue engineering is a concept for creating transplantable. To successfully provoke tissue regeneration, natural or synthetic. In myocardial tissue regeneration, previous studies have confirmed heart function improvement after cell. This article focuses on bottomup fabrication of functional tissue by cell sheet engineering. Bone marrowderived mesenchymal stem cells bmscs are the most frequently used stem cells in cell therapy and tissue engineering. Evaluation of placental mesenchymal stem cell sheets for. Cell sheet technology and cell patterning for biofabrication. The development of a bioartificial skin facilitates the treatment of patients with deep burns and various skinrelated disorders. Tissue engineering interdisciplinary field that combines principles of biology and medicine with engineering.
Cells, scaffolds, and molecules for myocardial tissue engineering. Threedimensional tissue is fabricated by repeating the same. Liver the liver is an important organ in the body by taking part in protein synthesis, metabolism and detoxification 19. Part two focuses on tissue engineering for cardiac repair, including chapters on decellularized biologic scaffolds, synthetic scaffolds, cell sheet engineering, maturation of functional cardiac tissue patches, vascularized engineered tissues for in vivo and in vitro applications, and clinical considerations for cardiac tissue engineering. Human body has capacity to repair and regenerate image adapted from stupp, mrs bulletin 2005 skin bone intestine. Pulsatile myocardial tubes fabricated with cell sheet engineering. Corneal reconstruction with tissueengineered cell sheets.
Tissue engineering by selfassembly and bioprinting of. To date, most cell sheet studies use thermoresponsive systems. The methods for cell sheet preparation for tissue and organ reconstruction include single cell sheet implantation, cell sheets combined with scaffolds implantation and multilayer cell sheet implantation. In addition, tissue engineering treatments for cartilage repair have been established clinically but not wideare. Functional assessment of crosslinked porous gelatin. This paper summarizes cell sheet based tissue engineering and its satisfactory therapeutic effects on cardiac disease. To understand chondrocyte behavior and improve cell expansion in monolayer culture, this study investigated the effects of morphological changes and cellular aggregation on the maintenance of chondrogenic capacity by observing the expression patterns of chondrogenic.
Pirraco 1,2,3, haruko obokata 3, takanori iwata 3, alexandra p. Fda and used clinically as burr plugs and sheets for or bital floor reconstruction in more than 200 patients 49. We applied cell sheet tissues to repair disrupted structures. Cardiac myocyte sheets are harvested from temperatureresponsive culture dishes. Pdf cell sheetbased tissue engineering for fabricating. Cell and tissue engineering includes the study of cellular mechanics and cell signaling, mechanotransduction, biosystems engineering and computational biology, nanotechnology, microfluidics, biomems and gene chips, functional tissue engineering and biomaterials, tissue structurefunction and cell matrix interactions. The gene expressions of both cell sheets in vitro and the repaired tissue at one week after transplantation of each cell sheets in vivo were examined using real time pcr.
Numerous studies using various types of cell sheet have been reported table i, fig. Jun 12, 2019 reoperation associated with use of such materials would be greatly reduced through the use of live scaffoldless autologous tissue patches constructed from stacked cell sheets that have growth potential. Becker, department of polymer science and department of biomedical engineering, the university of akron, akron, ohio 44325, united states abstract. Cells, scaffolds, and molecules for myocardial tissue engineering jonathan leora, yoram amsalema, smadar cohenb. Our concept is tissue reconstruction, not from single cells, but from cell sheets. Fundamentals of tissue engineering in 1933, the concept of tissue engineering was first introduced when mouse tumor cells.
Cell sheet engineering for heart tissue repair sciencedirect. Stem cells and tissue derived stromal cells stimulate the repair of degenerated and injured tissues, motivating a growing number of cell based interventions in the musculoskeletal field. Nov 14, 2016 furthermore, the cell sheet technique, a cell delivery strategy that retains the autocrine function of the ecm in the same cells, has been incorporated into more and more applications in the study of tissue engineering repair of periodontal tissue 25, 34, and cell sheets constructed of cells derived from different tissues have been used in. Tissue engineering is the use of a combination of cells, engineering, and materials methods. They can develop into various tissue types including skin, cartilage, cardiac tissue, nerves, muscle, and bone. The development and application of the tissue engineering technique has shown a significant potential in regenerative medicine.
A proper periodontal tissue reconstruction around the dental implant has been demonstrated with a vertical alveolar bone regeneration using the dental follicle tissues in which the layered cell. Amniotic stem cells are the mixture of stem cells that can be obtained from the amniotic fluid as well as the amniotic membrane. To control cell phenotype and direct tissue formation is. Fabrication of functional threedimensional tissues by. Cardiac tissue engineering cell sheet regenerative medicine. Cell sheetbased tissue engineering for fabricating 3dimensional. Cell sheet tissue engineering is a scaffoldfree approach to regenerating damaged tissue cells. Labbe b, marceaufortier g, fradette j 2011 cell sheet technology for tissue engineering. Recently, a novel tissue engineering technology named cell sheet has been efficaciously utilized in the regeneration of bone, corneal, cardiac, tracheal and periodontal ligamentlike tissues. These hipscderived tevgs displayed mechanical strength comparable to that of native vessels used clinically as vascular grafts and maintained excellent patency and mechanical function following implantation into a rat model. Recent advances in engineered stem cellderived cell sheets for. In addition to twodimensional cell sheet manipulation, threedimensional cell sheet manipulation has been used in cardiac tissue engineering.
Reoperation associated with use of such materials would be greatly reduced through the use of live scaffoldless autologous tissue patches constructed from stacked cell sheets that have growth potential. Cell sheet tissue engineering is a concept for creating transplantable two. Applications of elastinlike polypeptides in tissue engineering. Marques 1,2, satoshi tsuneda 4, masayuki yamato 3, teruo okano 3, rui l. Jan 24, 2019 therefore, the development of alternative strategies for bone regeneration is required to solve these problems. Creation of cell film from cardiac cells and biomaterial sheet. Cell sheetbased tissue engineering has revealed great potential to fabricate 3d cardiac tissues and should. In contrast to cell injection, bioengineered tissue transplantation minimizes cell loss and has the potential to repair tissue defects. Cell sheet, as a scaffoldfree technique, has attracted research interest in the context of drug discovery and. Endothelial cell coculture within tissueengineered. Dec 27, 2017 the importance of prevascularization strategies for bone tissue engineering is also discussed, with an emphasis on recent work describing substitutes produced using cell sheet. Prevascularization enhances therapeutic effects of human. One of the key challenges of tissue engineering is. Design and construction of functional components that can be used for maintenance, replacement or regeneration of damaged biological tissues.
The synergistic combination of emerging advances in tissue fabrication and stem cell engineering promises new strategies for engineering autologous blood vessels that recapitulate not only the mechanical properties of native vessels but also their biological. Request pdf cell sheet engineering for heart tissue repair recently, myocardial tissue engineering has emerged as one of the most promising therapies for. However, several challenges stand in the way of the industrialization of cell sheet products and the widespread acceptance of regenerative medicine based on cell sheet engineering. Cell sheet engineering for heart tissue repair request pdf. Nanotechnology in the regeneration of complex tissues pdf.
A popular approach is scaffoldbased tissue engineering, which utilizes a biodegradable polymer scaffold for seeding cells. New hydrogels wither while stem cells flourish for tissue repair. Polyn isopropylacrylamide based smart surfaces for cell sheet tissue engineering by. To date, most cell sheet studies use thermoresponsive systems to detach cell sheets. Mesenchymal stem cells mscs are multilineage cells with the ability to selfrenew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Winnik2 1 institute of advanced biomedical engineering. The cells also have potential medical applications, especially in organ regeneration. The constructs were then incubated at 37c for 30 minutes to allow for the cell sheet to adhere to the adventitia surface. Cell sheet engineering for myocardial tissue reconstruction. Okano t 2006 polysurgery of cell sheet grafts overcomes. The cell sheet preserves cell cell junctions, extracellular matrix ecm, and cell matrix connections thus restricting the cells to the wound bed 16.
We assessed placental mesenchymal stem cells pmscs as a potential cell source for cardiac repair and regeneration. Cell sheet harvest technology is important for producing viable, transplantable cell sheets and applying them to tissue engineering. Cell sheet tissue engineering for heart failure springerlink. Degradable adhesives for surgery and tissue engineering vrushali bhagat and matthew l. However, the limitations of conventional tissue engineering methods cell suspensions, scaffolds andor growth factors restrict its application in certain fields. Cartilage repair using cell sheet engineering in rat model ryo shimizu, naosuke kamei, md, phd, michio hamanishi, mitsuo ochi. Panel e shows a transmission electron micrograph of developed microvilli on the apical surface of the cell sheet. Tissue engineering involves the use of a tissue scaffold for the formation of new viable tissue for a medical purpose. Cell and tissue engineering biomedical engineering. The actual success of producing a cell sheet did not, however, become a reality until the discovery of thermoresponsive polymer surface technology in 1990 1. Stem cells for tissue science and engineering various tissues of the adult body have been used as a source of stem cells e.
The aim of cell therapies is to facilitate tissue repair by tissue replacement or the stimulation of local healing through paracrine secretion. Cell sheet techniques have great potential in this area. On the other hand, we have developed cell sheet engineering as scaffoldless tissue engineering, and applied it for myocardial tissue engineering. Pdf tissue engineering based on cell sheet technology. Paradigm of tissue engineering cells harvested from patient expanding cells mechanical andor molecular signalling. Using temperatureresponsive culture surfaces, cells can be harvested as intact sheets and cell dense thick tissues are constructed by layering these cell sheets. The use of cultured stem andor progenitor cells has the potential to improve the extent of regeneration, and also increases the likelihood that the transplant ed tissue will integrate with the surrounding tissue. Cell therapy is a new concept to repair diseased organs. Special issue potential application of cell sheets, for. Cellular engineering focuses on cell level phenomena, while tissue engineering and regenerative medicine seek to generate or stimulate new tissue. Cell sheets for tissue engineering applications springerlink. Our findings suggest that the gelatin discs with enlarged pore structure have potential as cell sheet carriers for intraocular delivery and corneal tissue engineering.
Additionally, induced pluripotent stem cell and embryonic stem cell. The layer can then be rolled up and subjected to static tension for a desired period of time. Besides their adhesiveness to plastic surfaces and their extensive differentiation potential in vitro, mscs are easily accessible, expandable in. The goal of tissue engineering is to repair or replace the damaged organ or tissues by delivering functional. Cell sheet engineering for integrating functional tissue.
Endothelial progenitor cells improve the therapeutic effect. Application of the cell sheet technique in tissue engineering. The application of cell sheet engineering in the vascularization of. Furthermore, induced pluripotent stem cell derived cell sheets have been indicated to possess higher potential for mi therapy than other stem cell derived. Additionally, induced pluripotent stem ips cell and embryonic stem cell escderived cell sheets have been proposed for tissue regeneration.
Cell sheet tissue engineering for scaffoldfree three. Mar 14, 2018 dedifferentiation of chondrocytes during cell expansion is one of the barriers in tissue construction for cartilage repair. There is much interest in engineering scaffoldfree tissue replacements. Chondrocytes for cartilage repair aci intervertebral disc cells for herniated disc stem cells into spinal cord lesions stem cells into brain lesions myoblasts and stem cells for myocardial infarction. In this rat model, asc sheet transplantation was technically successful. Various tissue engineering techniques have been created in research spanning two centuries, resulting in new opportunities for growing cells in culture and the creation of 3d tissue like constructs. Sep 29, 2015 however, due to the complexity of the regeneration of periodontal tissue and specificity of defects, the application of tissue engineering to periodontal tissue repair has been limited thus far. Human ips cellengineered cardiac tissue sheets with. Application of stem cells in tissue engineering for.
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