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1.
Adv Sci (Weinh) ; : e2401415, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965824

RESUMO

Galactic cosmic radiation (GCR) is one of the most serious risks posed to astronauts during missions to the Moon and Mars. Experimental models capable of recapitulating human physiology are critical to understanding the effects of radiation on human organs and developing radioprotective measures against space travel exposures. The effects of systemic radiation are studied using a multi-organ-on-a-chip (multi-OoC) platform containing engineered tissue models of human bone marrow (site of hematopoiesis and acute radiation damage), cardiac muscle (site of chronic radiation damage) and liver (site of metabolism), linked by vascular circulation with an endothelial barrier separating individual tissue chambers from the vascular perfusate. Following protracted neutron radiation, the most damaging radiation component in deep space, a greater deviation of tissue function is observed as compared to the same cumulative dose delivered acutely. Further, by characterizing engineered bone marrow (eBM)-derived immune cells in circulation, 58 unique genes specific to the effects of protracted neutron dosing are identified, as compared to acutely irradiated and healthy tissues. It propose that this bioengineered platform allows studies of human responses to extended radiation exposure in an "astronaut-on-a-chip" model that can inform measures for mitigating cosmic radiation injury.

2.
Cell Rep ; 43(6): 114302, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38824644

RESUMO

Resident cardiac macrophages are critical mediators of cardiac function. Despite their known importance to cardiac electrophysiology and tissue maintenance, there are currently no stem-cell-derived models of human engineered cardiac tissues (hECTs) that include resident macrophages. In this study, we made an induced pluripotent stem cell (iPSC)-derived hECT model with a resident population of macrophages (iM0) to better recapitulate the native myocardium and characterized their impact on tissue function. Macrophage retention within the hECTs was confirmed via immunofluorescence after 28 days of cultivation. The inclusion of iM0s significantly impacted hECT function, increasing contractile force production. A potential mechanism underlying these changes was revealed by the interrogation of calcium signaling, which demonstrated the modulation of ß-adrenergic signaling in +iM0 hECTs. Collectively, these findings demonstrate that macrophages significantly enhance cardiac function in iPSC-derived hECT models, emphasizing the need to further explore their contributions not only in healthy hECT models but also in the contexts of disease and injury.


Assuntos
Células-Tronco Pluripotentes Induzidas , Macrófagos , Contração Miocárdica , Engenharia Tecidual , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Macrófagos/metabolismo , Engenharia Tecidual/métodos , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Miocárdio/citologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Diferenciação Celular , Sinalização do Cálcio
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