Cell sheet engineering for integrating functional tissue in vivo: Successes and challenges

MRS Bulletin ◽  
2017 ◽  
Vol 42 (05) ◽  
pp. 350-355 ◽  
Author(s):  
Nicholas Baksh ◽  
Nathan D. Gallant ◽  
Ryan G. Toomey

Abstract

2014 ◽  
Vol 446 (1) ◽  
pp. 335-340 ◽  
Author(s):  
Soichi Takagi ◽  
Tatsuya Shimizu ◽  
Goro Kuramoto ◽  
Ken Ishitani ◽  
Hideo Matsui ◽  
...  

2021 ◽  
Vol 22 (19) ◽  
pp. 10322
Author(s):  
Luong Huu Dang ◽  
Shih-Han Hung ◽  
Yuan Tseng ◽  
Ly Xuan Quang ◽  
Nhi Thao Ngoc Le ◽  
...  

Decellularization has emerged as a potential solution for tracheal replacement. As a fully decellularized graft failed to achieve its purposes, the de-epithelialization partial decellularization protocol appeared to be a promising approach for fabricating scaffolds with preserved mechanical properties and few immune rejection responses after transplantation. Nevertheless, a lack of appropriate concurrent epithelialization treatment can lead to luminal stenosis of the transplant and impede its eventual success. To improve re-epithelialization, autologous nasal epithelial cell sheets generated by our cell sheet engineering platform were utilized in this study under an in vivo rabbit model. The newly created cell sheets have an intact and transplantable appearance, with their specific characteristics of airway epithelial origin being highly expressed upon histological and immunohistochemical analysis. Subsequently, those cell sheets were incorporated with a partially decellularized tracheal graft for autograft transplantation under tracheal partial resection models. The preliminary results two months post operation demonstrated that the transplanted patches appeared to be wholly integrated into the host trachea with adequate healing of the luminal surface, which was confirmed via endoscopic and histologic evaluations. The satisfactory result of this hybrid scaffold protocol could serve as a potential solution for tracheal reconstructions in the future.


2018 ◽  
Vol 59 (3-4) ◽  
pp. 276-285 ◽  
Author(s):  
Hyoe Komae ◽  
Minoru Ono ◽  
Tatsuya Shimizu

Background: The development of regenerative medicine in recent years has been remarkable as tissue engineering technology and stem cell research have advanced. The ultimate goal of regenerative medicine is to fabricate human organs artificially. If fabricated organs can be transplanted medically, it will be the innovative treatment of diseases for which only donor organ transplantation is the definitive therapeutic method at present. Summary: Our group has reported successful fabrication of thick functional myocardial tissue in vivo and in vitro by using cell sheet engineering technology which requires no scaffolds. Thick myocardial tissue can be fabricated by stacking cardiomyocyte sheets on the vascular bed every 24 h, so that a vascular network can be formed within the myocardial graft. We call this procedure a multi-step transplantation procedure. After human-induced pluripotent stem cells were discovered and human cardiomyocytes became available, a thick, macroscopically pulsate human myocardial tissue was successfully constructed by using a multi-step transplantation procedure. Furthermore, our group succeeded in fabricating functional human myocardial tissue which can generate pressure. Here, we present our way of fabricating human myocardial tissue by means of cell sheet engineering technology. Key Messages: Our group succeeded in fabricating thick, functional human myocardium which can generate pulse pressure. However, there are still a few problems to be solved until clinically functional human cardiac tissue or a whole heart can be fabricated. Research on myocardial regeneration progresses at such a pace that we believe the products of this research will save many lives in the near future.


2020 ◽  
Vol 7 (2) ◽  
pp. 32 ◽  
Author(s):  
Hun-Jin Jeong ◽  
Hyoryung Nam ◽  
Jinah Jang ◽  
Seung-Jae Lee

It is difficult to fabricate tubular-shaped tissues and organs (e.g., trachea, blood vessel, and esophagus tissue) with traditional biofabrication techniques (e.g., electrospinning, cell-sheet engineering, and mold-casting) because these have complicated multiple processes. In addition, the tubular-shaped tissues and organs have their own design with target-specific mechanical and biological properties. Therefore, the customized geometrical and physiological environment is required as one of the most critical factors for functional tissue regeneration. 3D bioprinting technology has been receiving attention for the fabrication of patient-tailored and complex-shaped free-form architecture with high reproducibility and versatility. Printable biocomposite inks that can facilitate to build tissue constructs with polymeric frameworks and biochemical microenvironmental cues are also being actively developed for the reconstruction of functional tissue. In this review, we delineated the state-of-the-art of 3D bioprinting techniques specifically for tubular tissue and organ regeneration. In addition, this review described biocomposite inks, such as natural and synthetic polymers. Several described engineering approaches using 3D bioprinting techniques and biocomposite inks may offer beneficial characteristics for the physiological mimicry of human tubular tissues and organs.


2015 ◽  
Vol 103 (12) ◽  
pp. 3825-3833 ◽  
Author(s):  
Akiyuki Hasegawa ◽  
Yuji Haraguchi ◽  
Tatsuya Shimizu ◽  
Teruo Okano

2019 ◽  
Vol 20 (22) ◽  
pp. 5656 ◽  
Author(s):  
Min-Ah Koo ◽  
Mi Hee Lee ◽  
Jong-Chul Park

Cell sheet engineering has evolved rapidly in recent years as a new approach for cell-based therapy. Cell sheet harvest technology is important for producing viable, transplantable cell sheets and applying them to tissue engineering. To date, most cell sheet studies use thermo-responsive systems to detach cell sheets. However, other approaches have been reported. This review provides the progress in cell sheet detachment techniques, particularly reactive oxygen species (ROS)-responsive strategies. Therefore, we present a comprehensive introduction to ROS, their application in regenerative medicine, and considerations on how to use ROS in cell detachment. The review also discusses current limitations and challenges for clarifying the mechanism of the ROS-responsive cell sheet detachment.


2006 ◽  
Vol 116 (2) ◽  
pp. 193-203 ◽  
Author(s):  
Joseph Yang ◽  
Masayuki Yamato ◽  
Kohji Nishida ◽  
Takeshi Ohki ◽  
Masato Kanzaki ◽  
...  

Biomedicines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 55 ◽  
Author(s):  
Alex T. Ponce ◽  
Ka Lok Hong

The unique opportunity for aptamer uses in thrombotic events has sparked a considerable amount of research in the area. The short half-lives of unmodified aptamers in vivo remain one of the major challenges in therapeutic aptamers. Much of the incremental successful therapeutic aptamer stories were due to modifications in the aptamer bases. This mini-review briefly summarizes the successes and challenges in the clinical development of aptamers for thrombotic events, and highlights some of the most recent developments in using aptamers for anticoagulation monitoring.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hallie Thorp ◽  
Kyungsook Kim ◽  
Makoto Kondo ◽  
David W. Grainger ◽  
Teruo Okano

AbstractCell and tissue engineering approaches for articular cartilage regeneration increasingly focus on mesenchymal stem cells (MSCs) as allogeneic cell sources, based on availability and innate chondrogenic potential. Many MSCs exhibit chondrogenic potential as three-dimensional (3D) cultures (i.e. pellets and seeded biomaterial scaffolds) in vitro; however, these constructs present engraftment, biocompatibility, and cell functionality limitations in vivo. Cell sheet technology maintains cell functionality as scaffold-free constructs while enabling direct cell transplantation from in vitro culture to targeted sites in vivo. The present study aims to develop transplantable hyaline-like cartilage constructs by stimulating MSC chondrogenic differentiation as cell sheets. To achieve this goal, 3D MSC sheets are prepared, exploiting spontaneous post-detachment cell sheet contraction, and chondrogenically induced. Results support 3D MSC sheets’ chondrogenic differentiation to hyaline cartilage in vitro via post-contraction cytoskeletal reorganization and structural transformations. These 3D cell sheets’ initial thickness and cellular densities may also modulate MSC-derived chondrocyte hypertrophy in vitro. Furthermore, chondrogenically differentiated cell sheets adhere directly to cartilage surfaces via retention of adhesion molecules while maintaining the cell sheets’ characteristics. Together, these data support the utility of cell sheet technology for fabricating scaffold-free, hyaline-like cartilage constructs from MSCs for future transplantable articular cartilage regeneration therapies.


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