Biology subjects

Jensen, C. H.

Publications and source records attributed to Jensen, C. H..

3 recordsLinked to original sources

bioRxiv2026

Sustained 10% Oxygen Promotes Atrial Rather Than Ventricular Specification During Human iPSC-Cardiomyocyte Differentiation

Background: Induced pluripotent stem cell-derived ventricular cardiomyocytes (iPSC-vCMs) hold great promise for replacing ventricular cardiomyocytes lost after myocardial infarction. However, their immature phenotype limits successful engraftment by increasing the risk of post-transplant arrhythmias. In contrast to the atmospheric O2 used during most iPSC-vCM differentiations, O2 levels inside the developing heart remain low, but very little is known on the effect on O2 on iPSC-vCM differentiation. Methods: We used a GMP compliant Quad Physoxia glovebox platform providing continuous stable specified O2 tensions during all processes to simulate the in vivo O2 conditions more closely with the aim of improving iPSC-vCM maturation. Results: We demonstrate by single cell RNA sequencing, and data integration with datasets for human cardiomyocytes from the different heart chambers as well as cell morphology-, ploidy-, and functional studies, that sustained 10% O2 throughout iPSC-CM differentiation promotes atrial- instead of ventricular iPSC-CM subtype specification. Conclusions: While this rejects our original hypothesis and forces some concerns to iPSC-vCM manufacturing by sphere technology, these unexpected data may serve as an attractive and easy approach to refine atrial iPSC-CM specification to benefit their exponentially growing diagnostic-, cytotoxic-, and regenerative use.

cell biology↗

bioRxiv2026

Poor survival after myocardial infarction in immune deficient NXG B2m mice is alleviated by transplantation of induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) formulated as spheres, but not single cells

The human heart lacks cardiac stem cells and the ability to reestablish the loss of ventricular cardiomyocytes (vCMs) after myocardial infarction (MI) resulting in heart dysfunction. vCM replacement using intracardiac transplantation of human induced pluripotent stem cell (iPSC) derived vCMs represent a promising strategy for targeting MI, but low engraftment remains a challenge. Herein, we investigated whether formulation of ventricular iPSC-CMs (iPSC-vCM) as spheres (iPSC-vCMSphere) improves cell retention and cardiac function as directly compared to single-cells (iPSC-vCMSC) after transplantation in a new severely immunocompromised mouse model with MI. Recipient survival immediately after MI and intervention was poor for both Vehicle (50%) and iPSC-vCMSC (36%) groups, whereas 92% of iPSC-vCMSphere treated mice survived, which is comparable to non-immune deficient C57bl/6 mice (91%). All surviving and engrafted animals retained iPSC-vCMs in the infarct border zone at 8-weeks, and heart function remained similar between groups, although minor improvements were observed for iPSC-vCMSphere animals. Surprisingly, iPSC-vCMSpheres were less mature than iPSC-vCMSCs. Thus, our data suggest that iPSC-vCM sphere formulation may offer some benefits for intracardiac delivery as compared with single cell formulated iPSC-vCMs, and thus remains a promising candidate for reestablishing the lost CMs after MI in the future.

cell biology↗

bioRxiv2019

Hormones as adaptive control systems in juvenile fish

Growth is an important theme in many biological disciplines. Physiologists often relate growth rates to hormonal control of essential processes. Ecologists often study growth as function of gradients or combinations of environmental factors. Fewer studies have investigated the combined effects of environmental and hormonal control on growth. Here, we present an evolutionary optimization model of fish growth that combines internal regulation of growth by hormone levels with the external influence of food availability and predation risk. Hormones are represented by growth hormone, thyroid hormone and orexin functions. By studying a range from poor to rich environments, we find that the level of food availability in the environment results in different evolutionarily optimal strategies of hormone levels. With more food available, higher levels of hormones are optimal, resulting in higher food uptake and growth. By using this fitness-based approach we also find a consequence of evolutionary optimization of survival on optimal hormone use. Where foraging is risky, aerobic scope can be used strategically to increase the chance of escaping from predators. By comparing model results to empirical observations, many mechanisms can be recognized, for instance a change in pace-of-life due to resource availability, and reduced emphasis on reserves in more stable environments.\n\nSummary statementWe combine physiological, environmental and evolutionary aspects of fish growth in a state-dependent model where the optimal regulation of growth and survival is achieved through hormonal regulation of behaviour.

animal behavior and cognition↗