Engineered three-dimensional cardiac tissues maturing in a rotating wall vessel bioreactor remodel diseased hearts in rats with myocardial infarction

Development of composite functional tissue sheets using hiPSC-CMs and hADSCs to improve the cardiac function after myocardial infarction

“…Our previous studies have demonstrated that constructing and organizing hiPSC-CMs into tissue sheets using PLGA fiber scaffold in vitro could enhance their therapeutic capabilities after transplantation [ 17 , 19 , 34 ]. Additionally, we attempted to enhance the function of tissue sheets and their therapeutic effects in vivo through several methods, such as physical stimulation [ 20 ], utilization of pharmaceutical agents [ 18 ], and stacking multiple fibers [ 16 ]. However, despite improvements in engraft retention achieved through the above approaches, there are still remaining issues in therapeutic efficacy because of the limited paracrine functions of exogenous hiPSC-CMs [ 16 , 18 , 20 , 35 ].…”

“…Additionally, we attempted to enhance the function of tissue sheets and their therapeutic effects in vivo through several methods, such as physical stimulation [ 20 ], utilization of pharmaceutical agents [ 18 ], and stacking multiple fibers [ 16 ]. However, despite improvements in engraft retention achieved through the above approaches, there are still remaining issues in therapeutic efficacy because of the limited paracrine functions of exogenous hiPSC-CMs [ 16 , 18 , 20 , 35 ]. MSCs are considered a promising approach for repairing damaged myocardium after MI, improving LV function and remodeling, and enhancing neovascularization via various paracrine cytokines [ 36 ].…”

“…However, the cardiac functional recovery capacity of MSCs is limited owing to severe cell loss, uneven local distribution, and inability to restore the lost contractility necessary for proper electromechanical heart function. Several studies have demonstrated the potential of induced pluripotent stem cell-derived CMs (iPSC-CMs) to engraft and improve the performance of myocardium after MI [ [16] , [17] , [18] , [19] , [20] , [21] ]. Several iPSC-CMs are currently in the clinical trial phase [ 22 ].…”

“…In our previous studies, we have constructed 3D hiPSC-CM tissue sheets and 3D MSC tissue sheets using PLGA fiber scaffold [ 17 , 25 ]. Our tissue sheet technology based on PLGA fiber scaffold exhibits numerous advantages, including well-organized and thick tissue, abundant ECM deposition, enhanced secretion, simple construction methods, excellent operability, and ultimately contributes to MI therapy [ 13 , [16] , [17] , [18] , [19] , [20] , 25 ]. In addition, previous studies have demonstrated that MSCs can reduce the apoptosis, improve the maturation, and inhibit the immune rejection of CM [ [26] , [27] , [28] ].…”

Engineered Tissue for Cardiac Regeneration: Current Status and Future Perspectives

“…More recently, we developed large-scale functional cardiac patches by using PLGA scaffolds and iPSC-CMs and showed marked improvement in cardiac function with angiogenesis and antifibrotic effects in a porcine cardiomyopathy model [ 49 ]. In addition, our group engineered a three-dimensional cardiac patch in a rotating wall vessel bioreactor; in this way, more mature CMs were obtained and transplanted into rats with MI [ 50 ]. Lancaster et al developed a tissue patch composed of a bioabsorbable knitted mesh, human neonatal fibroblasts, and hiPSC-CMs.…”