Keratin Biomaterials Attenuate Hypoxia-Mediated Cell Toxicity

Brianna Lund, Lindsey Burleson, Mariah James, Stephanie Burris, Patrick Link, Mary Brinkley

Abstract


Myocardial infarction (MI) or heart attack is a leading cause of death in the United States. MI occurs when a coronary artery becomes occluded, leading to localized ischemia, which results in heart muscle cell death and propels the heart into an arrhythmic state. In this state, the heart cannot adequately deliver oxygen to tissues within the body. This can lead to death and/or longer-term congestive heart failure (CHF). Unfortunately, individuals that survive MI are plagued by problems associated with CHF due to damaged sustained to the heart muscle caused by the original MI injury –which never fully heals.  Regenerative medicine research focuses on improving long-term outcomes of MI survivors through several avenues of research 1) by providing healthy cells to the damaged region of the heart for regeneration and repair and 2) by rescuing pre-apoptotic cells from death. To this end, studies have shown that a biomaterial made from human hair, keratin, can be used as a carrier for cell delivery, but may also play a dual role in promoting cardiac regeneration after MI. In the current study, the feasibility of using keratin to attenuate in vitro-modeled MI cell death was investigated. Three objectives were completed. 1) An in vitro model of MI was developed to expose human umbilical vein endothelial cells (HUVECs) to low oxygen (hypoxia) using Anaerobic Gas Pouches. 2) HUVEC toxicity to hypoxia was measured to identify the duration of low oxygen exposure required to kill ~50% of cells. 3) The ability of keratin to rescue HUVECs from hypoxia-mediated cell toxicity was measured. The results showed that low oxygen conditions that mimic MI-induced hypoxia could be achieved using the method developed (1.43% dissolved oxygen). Cell toxicity to low oxygen was observed as a function of hypoxic exposure. Finally,  HUVECs treated with keratin and exposed to long-term hypoxia (72hrs) proliferated in response, indicating that keratin provides a protective effect to cells in hypoxia. These data provide preliminary evidence to support the further study of keratin as a biomaterial treatment for cells exposed to hypoxia.


Keywords


Hypoxia, Keratin, Myocardial Infarction, Regenerative Medicine, Apoptosis, HUVECs

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