An improved device for growing mini-organs in a dish has been developed

When it comes to human bodies, there is no such thing as typical. Variation is the norm. In recent years, the biological sciences have increased their focus on exploring the acute lack of standards among individuals, and medical and pharmaceutical researchers are asking questions about translating insights into biodiversity into more rigorous and compassionate care.

What if treatments were tailored to each patient? What would happen if we could predict the individual body’s response to a drug before trial-and-error treatment? Is it possible to understand the way a person’s illness begins and progresses so that we can know exactly how to treat it?

Dan HuhAssociate Professor at Department of Bioengineering at the University of Pennsylvania’s College of Engineering and Applied Sciences, he is searching for answers to these questions By replicating biological systems outside the body. These external versions of internal systems promise to enhance drug efficacy while providing new levels of knowledge about patient health.

innovative Organ-on-a-chip technologyor miniature versions of the body’s systems stored in plastic devices no bigger than a thumb drive, Huh has extended his attention to engineering miniature organs in a dish using the patient’s own cells.

A recent study published in nature ways helmed by Huh presents the OCTOPUS, a device that nurtures organs in a dish to unparalleled levels of maturity. Includes study leaders Estelle ParkPhD Student in Bioengineering, Tatyana KarakachevaAssociate director of the Gastrointestinal Epithelium Modeling Program Children’s Hospital of Philadelphia (CHOP) f Catherine Hamiltonassistant professor of pediatrics in Pennsylvania Perelman School of Medicine and Co-Director of the Gastrointestinal Epithelial Modeling Program at CHOP.

In the study, the team used OCTOPUS (areganoid cUlture-based tThree-dimensional areproduction splatform with Yurestricted sSoluble Signals Application) to learn more about the unique challenges faced by children with inflammatory bowel disease (IBD).

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“The goal of this research is to create devices that give cells an environment as close as possible to the human body,” says Park. “We want their development in the dish to match that of their source, so we have a replica to learn from.” In a world where over 90 percent of all systems fail, Park says. With preclinical studies in animals before testing in humans, and the ethics of both being complex, OCTOPUS will be an invaluable addition to current laboratory practice.”

First developed in 2009, these dish organs, known as “organoids,” have opened the doors to major improvements in medical research and patient care.

To make them, scientists collect an organ’s own stem cells and insert them into a drop of 3-D gel. Feeding on a carefully developed chemical diet, stem cells auto-regulate themselves in an immature organ.

Compared to the simple 2D cell cultures that form the backbone of laboratory testing, organelles contain a range of information. Organs are made up of a variety of cell types, and these cells are more than the sum of their biological material. They develop and function in communication with each other.

Organelles, unlike traditional cell cultures, allow these relationships to develop. They provide powerful tools for studying how organs develop and carry out their specialized functions.

By generating a wealth of hard-to-access data about human bodies, organoids reproduce healthy and abnormal aspects of individual patients’ organs. The more mature the organoid, the closer they get to the true complexity of the organ.

With OCTOPUS, Huh’s team has significantly advanced the frontiers of organic research, providing a platform superior to traditional gel droplets.

Octopus divides the soft hydrogel culture material into tentacle geometry. The ultra-thin radial culture chambers are located on a circular disk the size of a US quarter, allowing organoids to progress to an unprecedented degree of maturity.

“The limited maturation of tissues is a major problem in organoid and stem cell research,” Huh says.

Efforts to address this problem have mainly focused on biochemistry through the development of better media formulations that help stem cells differentiate into more mature tissues. As engineers, we approached this problem from a different perspective by paying more attention to the physical aspects of how organelles grow. Redesigning the 3D geometry of the hydrogel scaffold, we were able to engineer the biochemical environment of conventional culture models. OCTOPUS improves the transport of nutrients, oxygen, and growth factors without ever reformulating the biochemistry of the media. “

Paper also introduces an improved version of the platform, called OCTOPUS-EVO, that takes maturity to the next level. Transforming the insert into a segmented organ with careful control of its liquid environment, Huh’s team used a variety of organ cell types to create sophisticated organelles that developed functional blood vessels.

Huh says, “The beauty of our technology lies in its simplicity. We designed the device with usability above all else in mind. A simple input, OCTOPUS can be easily integrated into existing laboratory technologies. The technology is easy to adopt and ready to make an immediate impact.”

Hamilton, whose lab is currently using OCTOPUS to grow organoids to study gut diseases in children, describes the devices as transformative.

“The better medical researchers can faithfully reproduce the way an organ in the body works, the better they can predict a patient’s response,” says Hamilton. “This technology is exactly what we need to screen drugs, test treatments, prescribe healthy behaviors, and identify dysfunction. We’re learning new things every day.”

Reference: Park SE, Kang S, Paek J, et al. Engineering engineering of organoid culture to improve organogenesis in a dish. nat ways. 2022; 19 (11): 1449-1460. doi: 10.1038 / s41592-022-01643-8

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