“…The presence of ECs in the microenvironment may contribute to the superior survival duration of cardiomyocytes demonstrated within our engineered CP (Gao et al, ). This aligns with previous studies that have described coculture of different types of cells resulting in improved maturation of cells, neovessel formation, and cell viability (Jain, ; Koike et al, ; Mironov et al, ; Nakayama, ; Narmoneva, Vukmirovic, Davis, Kamm, & Lee, ). We also found that the enhancement of vasculogenesis in the infarcted area in the patch group may be related to the reduction of the scar area.…”
One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have recently developed 3D-bioprinted biomaterial-free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D-bioprinted cardiac patches. The cardiac patches were generated using 3D-bioprinting technology in conjunction with cellular spheroids created from a coculture of human-induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D-bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation.
“…The presence of ECs in the microenvironment may contribute to the superior survival duration of cardiomyocytes demonstrated within our engineered CP (Gao et al, ). This aligns with previous studies that have described coculture of different types of cells resulting in improved maturation of cells, neovessel formation, and cell viability (Jain, ; Koike et al, ; Mironov et al, ; Nakayama, ; Narmoneva, Vukmirovic, Davis, Kamm, & Lee, ). We also found that the enhancement of vasculogenesis in the infarcted area in the patch group may be related to the reduction of the scar area.…”
One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have recently developed 3D-bioprinted biomaterial-free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D-bioprinted cardiac patches. The cardiac patches were generated using 3D-bioprinting technology in conjunction with cellular spheroids created from a coculture of human-induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D-bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation.
“…In accordance with a previously described procedure [ 21 , 33 ], we constructed scaffold-free 3D implants (diameter: 4 mm; height: 6 mm) composed of 760 spheroids each containing 5 × 10 4 autologous AT-MSCs. The cross-sectional CT images obtained at 6 and 12 months after implantation in animal no.…”
Section: Discussionmentioning
confidence: 99%
“…When the mold was carefully removed, a columnar construct of 4 mm in diameter and 6 mm in height appeared and was used for autologous implantation (Figure 1 A). The general outline of this method of construction has already been reported [ 21 , 33 ]. Figure 1 Surgical procedure.…”
BackgroundOsteoarthritis (OA) is a major joint disease in humans and many other animals. Consequently, medical countermeasures for OA have been investigated diligently. This study was designed to examine the regeneration of articular cartilage and subchondral bone using three-dimensional (3D) constructs of adipose tissue-derived mesenchymal stem cells (AT-MSCs).MethodsAT-MSCs were isolated and expanded until required for genetical and immunological analysis and construct creation. A construct consisting of about 760 spheroids that each contained 5.0 × 104 autologous AT-MSCs was implanted into an osteochondral defect (diameter: 4 mm; depth: 6 mm) created in the femoral trochlear groove of two adult microminipigs. After implantation, the defects were monitored by computed tomography every month for 6 months in animal no. 1 and 12 months in animal no. 2.ResultsAT-MSCs were confirmed to express the premature genes and to be positive for CD90 and CD105 and negative for CD34 and CD45. Under specific nutrient conditions, the AT-MSCs differentiated into osteogenic, chondrogenic, and adipogenic lineages, as evidenced by the expressions of related marker genes and the production of appropriate matrix molecules. A radiopaque area emerged from the boundary between the bone and the implant and increased more steadily upward and inward for the implants in both animal no. 1 and animal no. 2. The histopathology of the implants after 6 months revealed active endochondral ossification underneath the plump fibrocartilage in animal no. 1. The histopathology after 12 months in animal no. 2 showed not only that the diminishing fibrocartilage was as thick as the surrounding normal cartilage but also that massive subchondral bone was present.ConclusionsThe present results suggest that implantation of a scaffold-free 3D construct of AT-MSCs into an osteochondral defect may induce regeneration of the original structure of the cartilage and subchondral bone over the course of 1 year, although more experimental cases are needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13018-015-0173-0) contains supplementary material, which is available to authorized users.
“…Several reports have suggested that co-culturing these different types of cells promotes cell maturation, development and vasculogenesis and improves cell viability [13][14][15][16][17][18][19][20] . 3) Scaffold-free tissue engineering using spheroids allows the spheroids to be handled, and when placed closely, to fuse into certain shapes.…”
Section: Discussionmentioning
confidence: 99%
“…3) Scaffold-free tissue engineering using spheroids allows the spheroids to be handled, and when placed closely, to fuse into certain shapes. Recent studies have reported the development of a robotic system for novel three-dimensional tissue engineering employing layer-by-layer additive robotic biofabrication using tissue spheroids 16,17 . The combined use of our co-cultured spheroids and these novel biofabrication technologies may make it possible to fabricate natural functional human tissues and entire organs.…”
We consider the application of our scaffold-free 3-dimensional tissue engineering technology to cardiac regeneration therapy is feasible and expect that this technology will become a promising tool for the treatment of end-stage heart failure.
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