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Category: biotech/medical – Page 1,174

Scientists’ use of hydrogel materials leads to stem cells developing like human embryos

Materials scientists at UNSW Sydney have shown that human pluripotent stem cells in a lab can initiate a process resembling the gastrulation phase—where cells begin differentiating into new cell types—much earlier than occurs in mother nature.

For an embryo developing in the womb, occurs at day 14. But in a dish in a lab at UNSW’s Kensington campus, Scientia Associate Professor Kris Kilian oversaw an experiment where a gastrulation-like event was triggered within two days of culturing in a unique biomaterial that, as it turned out, set the conditions to mimic this stage of embryo development.

“Gastrulation is the key step that leads to the human body plan,” says A/Prof. Kilian.

Vitamin D supplements reduce the risk of dynapenia in older people

Vitamin D plays an important role in the regulation of calcium and phosphorus absorption by the organism. It also helps keep the brain and immune system working. Researchers at the Federal University of São Carlos (UFSCar) in Brazil and University College London (UCL) in the United Kingdom have now shown that vitamin D supplementation reduces the risk of dynapenia in older people by 78%.

Dynapenia is an age-associated loss of muscle strength. It can be partially explained by muscle atrophy and is a major risk factor for physical incapacity later in life. People with dynapenia are more likely to fall, need to go to hospital, be prematurely institutionalized, and die.

An article on the study is published in the journal Calcified Tissue International and Musculoskeletal Research. The study was supported by FAPESP.

‘The Price of Immortality’: How long can gene therapy and cellular regeneration extend life?

In his lively tour of longevity science and pseudoscience, Ward, a British reporter, discovers that researchers are largely not as interested in immortality per se as much as in helping us live fulfilling, active lives until our final day. And while some immortalists hope the culmination of this effort will eventually lead us to never finding that day, Ward leaves the question open.

He begins at the Church of Perpetual Life, a congregation of people who, instead of seeking paradise after death, would rather avoid their demise altogether. There, Ward meets Neal VanDeRee, the church’s pastor, who practices intermittent fasting and envisions a future in which biotechnology advances faster than our bodies break down.

VanDeRee is working to reach what he and other immortalists call “escape velocity” by extending their lives until biotechnology progresses fast enough to keep them alive forever. Another immortalist, Aubrey de Grey, sees this moment as surprisingly close — within 20 to 30 years, or maybe even sooner. It’s quite a claim, but is it possible? “Either we’ll discover we can make people healthy for longer but our lifespan is quite set, as most gerontologists believe, or de Grey’s longevity escape velocity will be proven correct,” Ward writes, never quite telling us which future he is betting on.

Anti-cancer CAR-T therapy reengineers T cells to kill tumors — and researchers are expanding the limited types of cancer it can target

So we designed CAR-T cells to produce IL-2 using synNotch. Now, when a CAR-T cell encounters a tumor, it produces IL-2 within the tumor instead of outside it, avoiding causing harm to surrounding healthy cells. Because synNotch is able to bypass the barriers tumors put up, it is able to help T cells amp up and maintain the amount of IL-2 they can make, allowing the T cells to keep functioning even in a hostile microenvironment.

We tested our CAR-T cells modified with synNotch on mice with pancreatic cancer and melanoma. We found that CAR-T cells with synNotch-induced IL-2 were able to produce enough extra IL-2 to overcome the tumors’ defensive barriers and fully activate, completely eliminating the tumors. While all of the mice receiving synNotch modified CAR-T cells survived, none of the CAR-T-only mice did.

Furthermore, our synNotch modified CAR-T cells were able to trigger IL-2 production without causing toxicity to healthy cells in the rest of the body. This suggests that our method of engineering T cells to produce this toxic cytokine only where it is needed can help improve the effectiveness of CAR-T cells against cancer while reducing side effects.

In vivo measurement of human brain material properties under quasi-static loading

Computational modelling of the brain requires accurate representation of the tissues concerned. Mechanical testing has numerous challenges, in particular for low strain rates, like neurosurgery, where redistribution of fluid is biomechanically important. A finite-element (FE) model was generated in FEBio, incorporating a spring element/fluid–structure interaction representation of the pia–arachnoid complex (PAC). The model was loaded to represent gravity in prone and supine positions. Material parameter identification and sensitivity analysis were performed using statistical software, comparing the FE results to human in vivo measurements. Results for the brain Ogden parameters µ, α and k yielded values of 670 Pa, −19 and 148 kPa, supporting values reported in the literature. Values of the order of 1.2 MPa and 7.7 kPa were obtained for stiffness of the pia mater and out-of-plane tensile stiffness of the PAC, respectively. Positional brain shift was found to be non-rigid and largely driven by redistribution of fluid within the tissue. To the best of our knowledge, this is the first study using in vivo human data and gravitational loading in order to estimate the material properties of intracranial tissues. This model could now be applied to reduce the impact of positional brain shift in stereotactic neurosurgery.

Finite-element (FE)-based computational models of the human brain are an increasingly common research tool, with applications ranging from head impact to neurosurgery. Studies considering head impacts are generally concerned with traumatic brain injury (TBI), where a better understanding of the underlying mechanisms is essential for the development of prevention measures [1]. Within neurosurgery, efforts are primarily focused on tumour resection, where loss of cerebrospinal fluid (CSF) and tissue resection are responsible for much of the deformation [2]. Movement and deformation of the intact brain, known as brain shift, is clinically significant in stereotactic neurosurgical procedures such as deep brain stimulation where electrode placement accuracy correlates with patient outcomes [3].

Organotypic cultures as aging associated disease models

Aging remains a primary risk factor for a host of diseases, including leading causes of death. Aging and associated diseases are inherently multifactorial, with numerous contributing factors and phenotypes at the molecular, cellular, tissue, and organismal scales. Despite the complexity of aging phenomena, models currently used in aging research possess limitations. Frequently used in vivo models often have important physiological differences, age at different rates, or are genetically engineered to match late disease phenotypes rather than early causes. Conversely, routinely used in vitro models lack the complex tissue-scale and systemic cues that are disrupted in aging.