Conditioned medium from hypoxic cells protects cardiomyocytes against ischemia

Chanyshev, B.; Shainberg, Asher; Isak, Ahuva; Chepurko, Yelena; Porat, Eyal E.; Hochhauser, Edith

doi:10.1007/s11010-011-1169-7

Cited by 6 publications

(4 citation statements)

References 47 publications

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“…In the gradient condition, a pattern emerged that the normoxic side was typically more dysfunctional than the hypoxic side. Previous studies with conditioned medium have shown that hypoxic CMs secrete factors that can protect other CMs from ischemic stress ( 66 ). Thus, in the gradient tissues, hypoxic and normoxic CMs may be continuously exchanging factors that contribute to the observed phenotypes.…”

Section: Discussionmentioning

confidence: 99%

A myocardial infarct border-zone-on-a-chip demonstrates distinct regulation of cardiac tissue function by an oxygen gradient

et al. 2022

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After a myocardial infarction, the boundary between the injured, hypoxic tissue and the adjacent viable, normoxic tissue, known as the border zone, is characterized by an oxygen gradient. Yet, the impact of an oxygen gradient on cardiac tissue function is poorly understood, largely due to limitations of existing experimental models. Here, we engineered a microphysiological system to controllably expose engineered cardiac tissue to an oxygen gradient that mimics the border zone and measured the effects of the gradient on electromechanical function and the transcriptome. The gradient delayed calcium release, reuptake, and propagation; decreased diastolic and peak systolic stress; and increased expression of inflammatory cascades that are hallmarks of myocardial infarction. These changes were distinct from those observed in tissues exposed to uniform normoxia or hypoxia, demonstrating distinct regulation of cardiac tissue phenotypes by an oxygen gradient. Our border-zone-on-a-chip model advances functional and mechanistic insight into oxygen-dependent cardiac tissue pathophysiology.

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Section: Discussionmentioning

confidence: 99%

A myocardial infarct border-zone-on-a-chip demonstrates distinct regulation of cardiac tissue function by an oxygen gradient

et al. 2022

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“…Importantly, this effect was found to be as potent as that induced by EPC transplantation 35 . In more recent studies, hypoxic CM from cardiomyocyte hypoxic cultures was shown to protect isolated hearts against ischemia, reducing infarct size and improving the rate of contraction and relaxation, 36 while hypoxic CM from ASCs stimulated angiogenesis in subcutaneously implanted sponges to a greater extent than normoxic CM, an effect associated with increased paracrine VEGF and ANG production by hypoxic ASCs 37 …”

Section: Strategies Based On Hypoxic Pre-conditioning In Vitromentioning

confidence: 97%

Hypoxia-based strategies for angiogenic induction

Hadjipanayi

Schilling

2013

Organogenesis

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Therapeutic angiogenesis promises to aid the healing and regeneration of tissues suffering from a compromised vascular supply. Ischaemia therapy has so far primarily focused on delivering isolated angiogenic growth factors. The limited success of these strategies in clinical trials, however, is increasingly forcing researchers to recognize the difficulties associated with trying to mimic the angiogenic process, due to its natural complexity. Instead, a new school of thought is gradually emerging, focusing on how to induce angiogenesis at its onset, by utilizing hypoxia, the primary angiogenic stimulus in physiological, as well pathological states. This shift in therapeutic approach is underlined by the realization of the importance of depressed HIF-1 α-mediated gene programming in non-healing ischemic tissues, which could explain their apparent habituation to chronic hypoxic stress and the limited capacity to generate adaptive angiogenesis. Hypoxia-based strategies, then effectively aim to override the habituated angiogenic cellular response, re-start the regenerative process and drive it to completion. Here we make a distinction between those strategies that utilize hypoxia in vitro as a preconditioning tool to optimize the angiogenic potential of tissue/cells before transplantation, vs. strategies that aim to induce hypoxia-induced signaling in vivo, directly, through pharmacological means or gene transfer. We then discuss possible future directions for the field, as it moves into the phase of clinical trials.

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“…Soluble paracrine factors present in secretome have been shown to have an antiapototic paracrine effect essential for the improvement of heart function post-infarction. 26 For this reason, the antiapoptotic paracrine effect of the secretome loaded nanocomposite hydrogels was another focus of this study.…”

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confidence: 99%