Regenerative Therapies Using Cell Sheet-Based Tissue Engineering for Cardiac Disease

Haraguchi, Yuji; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

doi:10.4061/2011/845170

Cited by 55 publications

(36 citation statements)

References 58 publications

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“…When the temperature is dropped below 32°C, the surface becomes hydrophilic and the grafted polymer rapidly hydrates, making it expand and causing the cells to detach from the surface. When compared with enzymatic digestion of a scaffold, which often disrupts the cell-cell contacts, this innovative technology enables a cell sheet to be generated just by cooling the dishes to room temperature and using multiple layered cell sheets (20).…”

Section: Cell Sheet Engineeringmentioning

confidence: 99%

Myocardial cell sheet therapy and cardiac function

Fujita

Itabashi

Seki

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Heart failure (HF) is the leading cause of death in developed countries. Regenerative medicine has the potential to drastically improve treatment for advanced HF. Stem cell-based medicine has received attention as a promising candidate therapy over the past decade; however, it has not yet realized this potential in terms of reliability. The cell sheet is an innovative technology for constructing aligned graft cells, and several cell sources have been investigated for making a feasible cell sheet. The most representative thus far is skeletal myoblast, although such cells raise the issue of arrhythmogenicity. Regenerative cardiomyocytes (CMs) derived from pluripotent stem cells (PSCs), such as embryonic stem cells or induced PSCs, are the most promising, because a myocardial cell sheet (MCS) constructed with regenerative CMs can potentially enable contraction recovery and electromechanical coupling with host CMs. The functional outcomes of experimental MCS are reduction of ventricular wall stress and paracrine effects rather than contraction recovery. Several technical obstacles still hamper the clinical application of MCSs, with graft survival the most pivotal issue. Ischemia, apoptosis, inflammation, and immune response can all cause graft cell death, and a stable blood supply to the MCS is critical for successful engraftment. Ventricular tachycardia must also be considered in any myocardial cell therapy, and multiple layering of MCS (>3 layers) is necessary to reconstruct human myocardium. Innervation is also a potential issue. The future application of myocardial cell therapy with MCS for advanced HF depends on resolving these difficulties.

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Section: Cell Sheet Engineeringmentioning

confidence: 99%

Myocardial cell sheet therapy and cardiac function

Fujita

Itabashi

Seki

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…In an aqueous environment thermoresponsive surfaces exhibit reversible hydrophobic and hydrophilic properties above and below the lower critical solution temperature (LCST) facilitating the detachment of an intact cell sheet without the use of enzymatic treatments. The efficacy of pNIPAAm for generation of intact cell sheets for skin, cardiac, and periodontal reconstruction have been reported earlier [7, 8]. Copolymerization of pNIPAAm with glycidyl methacrylate allows modulation of LCST and also gives prospects of further modification by incorporation of biomolecules through the epoxy groups of the later [9].…”

Section: Introductionmentioning

confidence: 93%

N-Isopropylacrylamide-co-glycidylmethacrylate as a Thermoresponsive Substrate for Corneal Endothelial Cell Sheet Engineering

Madathil

Kumar

Kumary

2014

BioMed Research International

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Endothelial keratoplasty is a recent shift in the surgical treatment of corneal endothelial dystrophies, where the dysfunctional endothelium is replaced whilst retaining the unaffected corneal layers. To overcome the limitation of donor corneal shortage, alternative use of tissue engineered constructs is being researched. Tissue constructs with intact extracellular matrix are generated using stimuli responsive polymers. In this study we evaluated the feasibility of using the thermoresponsive poly(N-isopropylacrylamide-co-glycidylmethacrylate) polymer as a culture surface to harvest viable corneal endothelial cell sheets. Incubation below the lower critical solution temperature of the polymer allowed the detachment of the intact endothelial cell sheet. Phase contrast and scanning electron microscopy revealed the intact architecture, cobble stone morphology, and cell-to-cell contact in the retrieved cell sheet. Strong extracellular matrix deposition was also observed. The RT-PCR analysis confirmed functionally active endothelial cells in the cell sheet as evidenced by the positive expression of aquaporin 1, collagen IV, Na+-K+ ATPase, and FLK-1. Na+-K+ ATPase protein expression was also visualized by immunofluorescence staining. These results suggest that the in-house developed thermoresponsive culture dish is a suitable substrate for the generation of intact corneal endothelial cell sheet towards transplantation for endothelial keratoplasty.

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“…Importantly, such single-cell sheets can be stacked together up to 3 layers (;80 mm) to create a 3D cardiac construct without compromising the viability of the cardiomyocytes. [49][50][51] In vivo studies have demonstrated some functional integration of such cardiac cell sheets with the host myocardium. 52 The source of cardiomyocytes for cardiac cell sheet generation has since been expanded from neonatal rat cardiomyocytes to human cardiac-resident stem cells 53 and cardiomyocytes derived from mouse and human pluripotent stem cells.…”

Section: Cardiac Tissue Engineeringmentioning

confidence: 98%

Growing Vascularized Heart Tissue From Stem Cells

Lim

Hernández²,

Dusting³

2013

Journal of Cardiovascular Pharmacology

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The promise of stem cells to repair the heart after damage or heart attack has not been realized because most such cells are lost after transplantation. A new approach is to grow substantial viable pieces of cardiac tissue from human stem cells by cardiac tissue engineering. Such constructs must be fully vascularized and perfused to ensure the viability of clinically relevant volumes of tissue. This requires careful choice of cells, culture conditions, a biomaterial to act as scaffold, and crucial strategies for vascularization. Autologous stem cells with high plasticity, which would avoid the need for antirejection therapies after transplantation, are an attractive source of both cardiomyocytes and vascular cells. Most stem cells also have inherent paracrine activity, releasing cytoprotective factors and growth-promoting cytokines that can further stimulate tissue regeneration and neovascularization through recruitment of endogenous stem and progenitor cells. Current advances for growing vascularized and functional cardiac constructs with human stem cells are described, bringing us a step closer to the engineering of complex cardiac tissues such as pacemaker, conducting tissue, or contractile myocardial flaps ideal for transplantation. From studies in rats successful transplantation of thin constructs to the ventricle has been reported, but there remain further issues to resolve before larger human constructs will be available to test in the clinic.

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Regenerative Therapies Using Cell Sheet-Based Tissue Engineering for Cardiac Disease

Cited by 55 publications

References 58 publications

Myocardial cell sheet therapy and cardiac function

Myocardial cell sheet therapy and cardiac function

N-Isopropylacrylamide-co-glycidylmethacrylate as a Thermoresponsive Substrate for Corneal Endothelial Cell Sheet Engineering

Growing Vascularized Heart Tissue From Stem Cells

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