Researchers at the Moores Cancer Center at the University of California, San Diego Medical College and UC San Diego Health have removed nuclei from certain ubiquitous cells known as enucleation and used the genetically engineered cells as their own cargo carrier. Reported that it was successfully delivered. Accurate treatment of diseased tissue.
Survey results published in the December 20, 2021 issue Nature Biomedical Engineering..
By accurately targeting diseased cells and tissues and providing drugs and treatments, the therapeutic effect can be significantly enhanced while reducing side effects. In a new study, a team led by senior author Dr. Richard Kremke, a professor of pathology at the University of California, San Diego, will genetically modify mesenchymal stem cells (MSCs) to drive disease-seeking behavior and nucleate. Removed. While retaining the energy and protein-producing organelles needed for therapeutic function.
In a mouse model of acute inflammation and pancreatitis, researchers have referred to enucleated cells called “cargosites” as anti-inflammatory cytokines ( Immune response It can reduce inflammation and related illnesses, administer systemically to mice to produce high levels of bioactive therapeutics at the target location for several days, and improve the illness.
“These cargosites retain most of their cellular function, but they also have a significantly improved ability to deliver and deliver therapeutic agents to target tissues in a safe manner,” Kremke said. “It reduces the potential for unwanted side effects caused by the drug going elsewhere and has the potential to treat the disease by delivering the drug exactly where they can do the best. open.”
The authors stated that the use of enucleated and modified MSCs has several advantages over the approach of using intact cells as a delivery medium.
First, due to safety concerns, it is difficult to obtain regulatory approval for the clinical use of extensively engineered stem cells, which also have the ability to proliferate and differentiate.
Second, primary cells collected from donors for therapeutic delivery have limited bioengineering and therapeutic capacity.
Third, cargosite cannot perform new gene transcription, so after administration to the body, it has a clearer and more predictable fate, produces unwanted factors, differentiates into unwanted cell types, and is desirable. Eliminate the possibility of transplanting into tissue in no other way.
“This means that what you design in the lab ex vivo will work properly in vivo in your body,” says Klemke. “This makes the use of Calgosite more accurate and reliable.”
According to Kremke, the next step is to optimize the ability of cargosite to provide multiple different treatments for lesion tissue in vivo, exploring opportunities to manipulate and enucleate other cell types such as immunity. .. cell, And develop a similar approach to seek out and eradicate metastatic cancer that has spread throughout the body.
Huawei Wang et al, genetically engineered and enucleated human mesenchymal stromal cells for targeted delivery of therapeutic agents to lesioned tissue, Nature Biomedical Engineering (2021). DOI: 10.1038 / s41551-021-00815-9
University of California, San Diego
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Nucleus-free cells prove useful in delivering therapeutic agents to lesioned tissue
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