Induced Pluripotent Stem Cells as a Source of Extracellular Vesicles for Therapy

First generation stem cell therapies largely reduce chronic inflammation and, less reliably, increase regeneration via the effect of intracellular signals delivered by the transplanted cells. The transplanted cells die quite rapidly rather than surviving to integrate into tissues. Arguably a majority of intracellular signaling is carried by forms of extracellular vesicle, membrane-wrapped packages of molecules that pass between cells to influence their behavior. The contents of these vesicles are not well cataloged, but that isn't an obstacle to efforts to replace cell therapies with vesicle therapies, the vesicles harvested from cells that would otherwise have been transplanted. The use of vesicles rather than cells should present fewer logistical challenges when it comes to manufacture, storage, and quality control, and we might hope that this translates into faster progress and cheaper treatments in this branch of regenerative medicine.

Scientists report that adult cells reprogrammed to become primitive stem cells, called induced pluripotent stem cells (iPSCs), make more extracellular vesicles than other kinds of adult stem cells commonly used for this purpose in research. Extracellular vesicles are naturally abundant in many types of cells, which use the cargo-containing spheres to communicate with other cells. They are about one one-hundredth the diameter of a cell and can carry anything from fats and proteins to nucleic acids. When a cell releases an extracellular vesicle, other cells nearby slurp up the tiny packet and its contents, making it an attractive target for packaging treatments for diseased cells that are deteriorating or aging prematurely.

To package a potential treatment in an extracellular vesicle, scientists typically use a cell called a mesenchymal stem cell, which is found among fat or bone marrow cells and gives rise to other fat and bone cells. Scientists genetically modify the stem cell to produce vesicles with the treatment-related cellular therapy - usually a protein. But mesenchymal stem cells aren't the best sources for extracellular vesicles. The cells don't multiply as often as iPSCs, and more cells are necessary to produce larger quantities of extracellular vesicles needed for therapeutic use. In addition, mesenchymal cells grow best in a liquid called fetal bovine serum, which contains potentially treatment-contaminating extracellular vesicles that are difficult to distinguish and separate from extracellular vesicles derived from mesenchymal cells.

By contrast, the liquid used to store and feed human iPSCs in the laboratory, called Essential 8, is free of extracellular vesicles and animal proteins, and scientists found the cells could produce 16 times more vesicles than mesenchymal stem cells. "We wanted to show other scientists working on such potential therapies that human iPSCs can efficiently produce highly purified extracellular vesicles that could, one day, be used to treat aging-related diseases."



Why can't extra cellular vesicles just be mimicked with lipid nanoparticles which are essentially also membrane blobs?

Posted by: jimofoz at May 10th, 2019 6:28 AM

I think a combination would work best, and once we have a good catalog of the said vesicles, they might be delivered in higher concentration to skew the cellular processes in the desired direction

Posted by: Cuberat at May 10th, 2019 7:00 AM

@jimofoz: Because at this point it would be challenging to assemble the contents of the artificial vesicles, both on a practical basis of there being hundreds of different molecules, and on a knowledge basis of not yet knowing what all of those molecules are in any given situation. People are going to do this, of course, but I think that line of work has a lot of work ahead in it.

Posted by: Reason at May 10th, 2019 7:33 AM

Empty lipid nanovesicles are anti inflammatory in themselves.

Posted by: JLH at May 12th, 2019 9:36 AM

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