Nuclear-free carriers
Accurate delivery of drugs or instruments for therapy to diseased tissues significantly increases the effectiveness of treatment while reducing side effects, and also allows the drug to be injected into the body in much smaller quantities. Researchers from the University of California, San Diego School of Medicine and the Moores Cancer Center at the University of California, San Diego have created a safe means of delivering drugs to target tissues. To do this, they genetically modified mesenchymal stem cells (MSCs) so that they contained chemoattractant receptors (to move along the concentration gradient) and molecules binding endothelial cells, and then removed nuclei from them by centrifugation, preserving organelles that produce energy and proteins necessary to perform vital functions.
To test the quality of delivery by nuclear–free cells, a group led by Richard Klemke created so-called cargo cells (from the English "cargo" - cargo), filled them with anti-inflammatory cytokines and injected mouse models of acute inflammation and pancreatitis. Within a few days, cytokines accumulated in target tissues, where they changed the immune response and reduced the activity of inflammation, which was accompanied by relief of the course of the disease.
The researchers found that the cargo cells retained the ability to carry out most of their cellular functions, but also had the ability to safely transport and deliver therapeutic drugs specifically to target tissues. This opens up the possibility of treating diseases by delivering drugs exactly where they are needed, with less likelihood of undesirable side effects associated with the fact that these drugs arrive elsewhere.
The authors stated that the use of enucleated (stripped of nuclei) modified MSCs has a number of advantages compared to approaches in which full-fledged cells are used as delivery vehicles.
Firstly, it is difficult to obtain regulatory approval for the clinical use of significantly modified stem cells that have the ability to proliferate and differentiate for safety reasons.
Secondly, primary cells taken from donors for therapeutic delivery have limited bioengineering and therapeutic capabilities.
Thirdly, cargo cells have a more definite and predictable fate after introduction into the body: they cannot transcribe and produce undesirable factors, differentiate into undesirable cell types or take root in tissues with undesirable consequences.
The next steps of Klemke and his colleagues include the creation of cargo cells capable of delivering many different therapeutic agents to diseased tissues in vivo, the study of possibilities for the creation and enucleation of other cell types, including immune cells, and the development of a similar approach for the search and destruction of metastatic oncological diseases.
Article H.Wang et al. Genetically engineered and enucleated human mesenchymal stromal cells for the targeted delivery of therapeutics to diseased tissue is published in the journal Nature Biomedical Engineering:
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of UC San Diego: Nuclei-free Cells Prove Utility in Delivering Therapeutics to Diseased Tissues.