Toggle light / dark theme

From Neuronal Differentiation of iPSCs to 3D Neuro-Organoids: Modelling and Therapy of Neurodegenerative Diseases

In the last decade, the advances made into the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) led to great improvements towards their use as models of diseases. In particular, in the field of neurodegenerative diseases, iPSCs technology allowed to culture in vitro all types of patient-specific neural cells, facilitating not only the investigation of diseases’ etiopathology, but also the testing of new drugs and cell therapies, leading to the innovative concept of personalized medicine. Moreover, iPSCs can be differentiated and organized into 3D organoids, providing a tool which mimics the complexity of the brain’s architecture. Furthermore, recent developments in 3D bioprinting allowed the study of physiological cell-to-cell interactions, given by a combination of several biomaterials, scaffolds, and cells.

Advantages of CRISPR-Cas9 combined organoid model in the study of congenital nervous system malformations

In the past 10 years, gene-editing and organoid culture have completely changed the process of biology. Congenital nervous system malformations are difficult to study due to their polygenic pathogenicity, the complexity of cellular and neural regions of the brain, and the dysregulation of specific neurodevelopmental processes in humans. Therefore, the combined application of CRISPR-Cas9 in organoid models may provide a technical platform for studying organ development and congenital diseases. Here, we first summarize the occurrence of congenital neurological malformations and discuss the different modeling methods of congenital nervous system malformations. After that, it focuses on using organoid to model congenital nervous system malformations. Then we summarized the application of CRISPR-Cas9 in the organoid platform to study the pathogenesis and treatment strategies of congenital nervous system malformations and finally looked forward to the future.

Keywords: organoid, CRISPR-Cas9, congenital nervous system malformation, central nervous system, 3D

Genetic Modification of Brain Organoids

Brain organoids have become increasingly used systems allowing 3D-modeling of human brain development, evolution, and disease. To be able to make full use of these modeling systems, researchers have developed a growing toolkit of genetic modification techniques. These techniques can be applied to mature brain organoids or to the preceding embryoid bodies (EBs) and founding cells. This review will describe techniques used for transient and stable genetic modification of brain organoids and discuss their current use and respective advantages and disadvantages. Transient approaches include adeno-associated virus (AAV) and electroporation-based techniques, whereas stable genetic modification approaches make use of lentivirus (including viral stamping), transposon and CRISPR/Cas9 systems. Finally, an outlook as to likely future developments and applications regarding genetic modifications of brain organoids will be presented.

The development of brain organoids (Kadoshima et al., 2013; Lancaster et al., 2013) has opened up new ways to study brain development and evolution as well as neurodevelopmental disorders. Brain organoids are multicellular 3D structures that mimic certain aspects of the cytoarchitecture and cell-type composition of certain brain regions over a particular developmental time window (Heide et al., 2018). These structures are generated by differentiation of induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) into embryoid bodies followed by, or combined, with neural induction (Kadoshima et al., 2013; Lancaster et al., 2013). In principle, two different classes of brain organoid protocols can be distinguished, namely: (i) the self-patterning protocols which produce whole-brain organoids; and (ii) the pre-patterning protocols which produce brain region-specific organoids (Heide et al., 2018).

Musk’s Neuralink says the first human to have a chip implanted in his brain can now play video games using his mind

The first patient of Elon Musk’s Neuralink has been presented to the public. Noland Arbaugh had all but given up playing Civilization VI ever since a diving accident dislocated two vertebrae in his cervical spinal cord, leaving him paralyzed from the shoulders down.

When confined to his wheel chair, the 29-year-old American is totally dependent on the care of his parents, who need to shift his weight ever few hours to avoid pressure sores from sitting too long in the same position.

Moving a cursor on a display furthermore required the use of a mouth stick, a specialized assistive device used by quadriplegics.

‘Like a Lab in your Pocket’ — new test strips raise game in gene-based diagnostics

Biosensing technology developed by engineers has made it possible to create gene test strips that rival conventional lab-based tests in quality. When the pandemic started, people who felt unwell had to join long queues for lab-based PCR tests and then wait for two days to learn if they had the COVID-19 virus or not.

In addition to significant inconvenience, a major drawback was the substantial and expensive logistics needed for such laboratory tests, while testing delays increased the risk of disease spread.

Now a team of bio]medical engineers at UNSW Sydney have developed a new technology offering test strips which are just as accurate as the lab-based detection. And according to research published today in Nature Communications, it’s not just public health that the technology may benefit.

Nanosurgical Tool could be Key to Cancer Breakthrough

A groundbreaking nanosurgical tool — about 500 times thinner than a human hair — could be transformative for cancer research and give insights into treatment resistance that no other technology has been able to do, according to a new study.

The high-tech double-barrel nanopipette, developed by University of Leeds scientists, and applied to the global medical challenge of cancer, has — for the first time — enabled researchers to see how individual living cancer cells react to treatment and change over time — providing vital understanding that could help doctors develop more effective cancer medication.

The tool has two nanoscopic needles, meaning it can simultaneously inject and extract a sample from the same cell, expanding its potential uses. And the platform’s high level of semi-automation has sped up the process dramatically, enabling scientists to extract data from many more individual cells, with far greater accuracy and efficiency than previously possible, the study shows.

A Digital Twin Might Just Save Your Life

In the last decade, thanks to advances in AI, the internet of things, machine learning and sensor technologies, the fantasy of digital twins has taken off. BMW has created a digital twin of a production plant in Bavaria. Boeing is using digital twins to design airplanes. The World Economic Forum hailed digital twins as a key technology in the “fourth industrial revolution.” Tech giants like IBM, Nvidia, Amazon and Microsoft are just a few of the big players now providing digital twin capabilities to automotive, energy and infrastructure firms.

The inefficiencies of the physical world, so the sales pitch goes, can be ironed out in a virtual one and then reflected back onto reality. Test virtual planes in virtual wind tunnels, virtual tires on virtual roads. “Risk is removed” reads a recent Microsoft advertorial in Wired, and “problems can be solved before they happen.”

All of a sudden, Dirk Helbing and Javier Argota Sánchez-Vaquerizo wrote in a 2022 paper, “it has become an attractive idea to create digital twins of everything.” Cars, trains, ships, buildings, airports, farms, power plants, oil fields and entire supply chains are all being cloned into high-fidelity mirror images made of bits and bytes. Attempts are being undertaken to twin beaches, forests, apple orchards, tomato plants, weapons and war zones. As beaches erode, forests grow and bombs explode, so too will their twins, watched closely by technicians for signals to improve outcomes in the real world.

Bird flu is decimating seal colonies. Scientists don’t know how to stop it

PORTLAND, Maine (AP) — Avian influenza is killing tens of thousands of seals and sea lions in different corners of the world, disrupting ecosystems and flummoxing scientists who don’t see a clear way to slow the devastating virus.

The worldwide bird flu outbreak that began in 2020 has led to the deaths of millions of domesticated birds and spread to wildlife all over the globe. This virus isn’t thought to be a major threat to humans, but its spread in farming operations and wild ecosystems has caused widespread economic turmoil and environmental disruptions.

Seals and sea lions, in places as far apart as Maine and Chile, appear to be especially vulnerable to the disease, scientists said. The virus has been detected in seals on the east and west coasts of the U.S., leading to deaths of more than 300 seals in New England and a handful more in Puget Sound in Washington. The situation is even more dire in South America, where more than 20,000 sea lions have died in Chile and Peru and thousands of elephant seals have died in Argentina.