Generation of a Human Cardiac Patch Based on a Reendothelialized Biological Scaffold (BioVaSc)

Abstract

Despite improvements in acute care, ischemic heart disease remains the major cause of death worldwide. [1] For the treatment of heart infarction or heart failure, stem cell therapies have emerged as a therapeutic option. Although data from first clinical trials revealed promising safety profiles with moderate Although there are improvements in acute care, ischemic heart disease is the major cause of death worldwide. As a treatment for heart failure or heart infarction, stem cell therapies emerged as a potential therapeutic option. First results have shown moderate improvements and have revealed several limitations, such as an insufficient retention, homing, and engraftment of the cells. These drawbacks result in a loss of cells shortly after implantation. To overcome these hurdles, a human cardiac patch is developed in this work, using a biological collagen-based vascularized scaffold (BioVaSc ® ). Endothelial cells are cultured in the pre-existing vascular structure to establish a physiological blood-tissue interface. A co-culture of fibroblasts, mesenchymal stem cells, and induced-pluripotent-stem-cell-derived cardiomyocytes is seeded on the vascularized scaffold. After two weeks, physiological cardiac functions and expression of cardiac-specific markers is detected. Moreover, physiological beating rates as well as responsiveness to drug treatment and electrical stimulation is observed. Bioreactor culture facilitates long-term culture up to four months. Due to its tissue characteristics, the patch constitutes a promising tool for drug development, in addition to its potential in clinical applications.

Bioreactors for Cardiac Tissue Engineering

“…After implantation, these constructs showed the formation of capillary networks congruent with the amount of ECs seeded . Recently, Schürlein et al developed a vascularized human cardiac patch based on a reendothelialized biological scaffold (BioVaSc) ( Figure ) . Various physiological cardiac functions and expression of cardiac‐specific markers were detected after 2 weeks.…”

“…A fluid system composed of a medium reservoir flask and a pressure flask in which pressure curves of 120 80 mmHg ‐1 at 1 Hz were generated enabled a physiological perfusion of the vasculature. Reproduced with permission . Copyright 2017, Wiley‐VCH.…”

“…Based on literature data, several research efforts have been made to engineer novel constructs with CTE potentialities, though using different methods and materials. Among them, the development of bioreactor‐based systems, with requisite features, has gained particular interest that produces clinically effective cardiovascular tissue‐based constructs . For a said purpose, a bioreactor‐based system for TE applications should possess/offer the following criteria, i.e., 1) uniform cell distribution, 2) controlled maintenance of physicochemical requirements of the cell, e.g., i) O 2 , ii) growth nutrients, and iii) growth factors, etc., 3) controlled mixing system for diffusion and convection purposes, 4) increased mass transport and proper distribution of culture medium, 5) cell exposure to physicochemical and electrical stimuli, 6) provide stability and maintain scaffold properties, 7) control monitoring of target phenotypes, 8) control functional maturation of 3D substitutes, 9) establish a substantial level of cellular distribution, 10) proper waste exchange and management, 11) reduce excessive turbulence in the fluid flow, 12) maintain a high degree of reproducibility, and 13) control monitoring and precise automation, etc.…”

Flexible tissue-like electrode as a seamless tissue-electronic interface

“…Fibers appear in gray, cardiac troponin T (cTnT) in green, and the cell nuclei in blue. (I) Schematic drawing of an advanced co-culture composed of hiPSC-CM, mesenchymal stromal cells (MSC), and hdF [19]. A high integration of the cardiac tissue into the porous scaffold was demonstrated by (J) SEM imaging and (K) confocal microscopy.…”

“…To prove that the porous carbon fiber scaffolds can be embedded into a relevant target tissue, the scaffolds were used in a tissue engineering approach. Therefore, a co-culture system was established as previously described [19]. Due to their role in cardiac repair, hDF and mesenchymal stromal stem cells [21] were included, and the constructs were exposed to long-term culture conditions ( Figure 3I).…”