Cardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limited. We have established a scaffold-free protocol to generate multicellular, beating human cardiac microtissues in vitro from hiPSCs-namely human organotypic cardiac microtissues (hOCMTs)-that show some degree of self-organization and can be cultured for long term. This is achieved by the differentiation of hiPSC in 2D monolayer culture towards cardiovascular lineage, followed by further aggregation on low-attachment culture dishes in 3D. The generated hOCMTs contain multiple cell types that physiologically compose the heart and beat without external stimuli for more than 100 days. We have shown that 3D hOCMTs display improved cardiac specification, survival and metabolic maturation as compared to standard monolayer cardiac differentiation. We also confirmed the functionality of hOCMTs by their response to cardioactive drugs in long-term culture. Furthermore, we demonstrated that they could be used to study chemotherapy-induced cardiotoxicity. Due to showing a tendency for self-organization, cellular heterogeneity, and functionality in our 3D microtissues over extended culture time, we could also confirm these constructs as human cardiac organoids (hCOs). This study could help to develop more physiologically-relevant cardiac tissue models, and represent a powerful platform for future translational research in cardiovascular biology.
- MeSH
- Cell Differentiation physiology MeSH
- Induced Pluripotent Stem Cells * MeSH
- Myocytes, Cardiac metabolism MeSH
- Cardiovascular Agents * metabolism MeSH
- Humans MeSH
- Antineoplastic Agents * metabolism MeSH
- Heart physiology MeSH
- Tissue Engineering methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Mechanobiology-on-a-chip is a growing field focusing on how mechanical inputs modulate physico-chemical output in microphysiological systems. It is well known that biomechanical cues trigger a variety of molecular events and adjustment of mechanical forces is therefore essential for mimicking in vivo physiologies in organ-on-a-chip technology. Biomechanical inputs in organ-on-a-chip systems can range from variations in extracellular matrix type and stiffness and applied shear stresses to active stretch/strain or compression forces using integrated flexible membranes. The main advantages of these organ-on-a-chip systems are therefore (a) the control over spatiotemporal organization of in vivo-like tissue architectures, (b) the ability to precisely control the amount, duration and intensity of the biomechanical stimuli, and (c) the capability of monitoring in real time the effects of applied mechanical forces on cell, tissue and organ functions. Consequently, over the last decade a variety of microfluidic devices have been introduced to recreate physiological microenvironments that also account for the influence of physical forces on biological functions. In this review we present recent advances in mechanobiological lab-on-a-chip systems and report on lessons learned from these current mechanobiological models. Additionally, future developments needed to engineer next-generation physiological and pathological organ-on-a-chip models are discussed.
- Publication type
- Journal Article MeSH
- Review MeSH
6. Aufl. 293 s.
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- anesteziologie a intenzivní lékařství
- urgentní lékařství
xiii, 355 s. : il. ; 25 cm
- MeSH
- Multiple Organ Failure physiopathology MeSH
- Nitric Oxide physiology therapeutic use MeSH
- Sepsis physiopathology MeSH
- Shock, Septic physiopathology MeSH
- Shock physiopathology MeSH
- Heart physiology MeSH
- Publication type
- Congress MeSH
- Collected Work MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- traumatologie
- urgentní lékařství
Fibrin sealing in surgical and nonsurgical fields ; Vol. 1
[ 1st ed.] 150 s. : 56 obr., přeruš. lit.,rejstř. ; 23 cm
x, 416 s. : il., tab. ; 25 cm
- MeSH
- Cytokines physiology therapeutic use MeSH
- Multiple Organ Failure MeSH
- Sepsis MeSH
- Shock, Septic MeSH
- Shock immunology MeSH
- Publication type
- Congress MeSH
- Collected Work MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- traumatologie
- urgentní lékařství
- biochemie
[1st ed.] XIX, 1163 s. : tab., grafy.,obr., přeruš.lit., věc.+aut.rejstř. ; 32 cm
- Keywords
- Shock, Sepsis, Syndrome Multi-Organ-Dysfunction,
- MeSH
- Multiple Organ Failure physiopathology MeSH
- Sepsis MeSH
- Shock physiopathology MeSH
- Shock, Traumatic physiopathology MeSH
- Conspectus
- Lékařské vědy. Lékařství
- NML Fields
- traumatologie
- patologie
- fyziologie
[1st ed.] XIX, 1163 s. : tab., grafy.,obr., přeruš.lit., věc.+aut.rejstř. ; 32 cm
