Ex vivo in the context of "Vasculature"

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⭐ Core Definition: Ex vivo

Ex vivo (Latin for 'out of the living') refers to biological studies involving tissues, organs, or cells maintained outside their native organism under controlled laboratory conditions. By carefully managing factors such as temperature, oxygenation, nutrient delivery, and perfusing a nutrient solution through the tissue's vasculature, researchers sustain function long enough to conduct experiments that would be difficult or unethical in a living body. Ex vivo models occupy a middle ground between in vitro (lit.'in the glass') models, which typically use isolated cells, and in vivo (lit.'in the living') studies conducted inside living organisms.

Ex vivo platforms support pharmacologic screening, toxicology testing, transplant evaluation, developmental biology, and investigations of disease-mechanism research across medicine and biology, from cardiology and neuroscience to dermatology and orthopedics. Because they often use human tissues obtained from clinical procedures or biobanks, they can reduce reliance on live-animal experimentation; their utility, however, is limited by finite viability, incomplete systemic integration, and post-mortem biochemical changes that accumulate over time. The earliest perfusion studies were conducted in the mid-19th century, and subsequent advances in sterilization, imaging, and microfluidics have facilitated broader adoption into the 20th and 21st centuries. Regulatory oversight depends on specimen origin: human ex vivo research is subject to informed consent, whereas animal-derived models fall under institutional animal care guidelines.

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Ex vivo in the context of Gene therapy

Gene therapy is medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.

The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I. In 2003, Gendicine became the first gene therapy to receive regulatory approval. Since that time, further gene therapy drugs were approved, such as alipogene tiparvovec (2012), Strimvelis (2016), tisagenlecleucel (2017), voretigene neparvovec (2017), patisiran (2018), onasemnogene abeparvovec (2019), idecabtagene vicleucel (2021), nadofaragene firadenovec, valoctocogene roxaparvovec and etranacogene dezaparvovec (all 2022). Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. AAVs are characterized by stabilizing the viral capsid, lower immunogenicity, ability to transduce both dividing and nondividing cells, the potential to integrate site specifically and to achieve long-term expression in the in-vivo treatment. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters.

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