More Evidence for Exosomes to be Important in the Outcome of Stem Cell Therapies

Stem cell therapies produce benefits, but for most of the presently available treatments this appears to be the result of changes in the signaling environment rather than any other activity on the part of the transplanted cells. The newly introduced stem cells fail to integrate with local tissues and typically don't last long after transplantation. So what exactly produces the observed beneficial changes in cellular behavior, level of inflammation, and degree of regeneration? There are no doubt many distinct mechanisms, as nothing is ever simple when it comes to cell biology, but of late researchers have focused on a role for exosomes. These are membrane-wrapped packages that cells pass between one another, and they appear to be involved in many cellular processes, though at present are only very partially cataloged and understood. If it turns out that they are a primary mechanism by which transplanted stem cells alter the behavior of local cells, then it should be possible to build therapies that deliver only exosomes:

Exosomes are tiny membrane-enclosed packages that form inside of cells before getting expelled. Long thought of as part of a cellular disposal system, scientists have more recently discovered that exosomes are packed with proteins, lipids and gene-regulating RNA. Studies have shown that exosomes from one cell can be taken up by another by fusing with the target cell's membrane, spurring it to make new proteins. Exosomes also facilitate cell-to-cell interactions and play a signaling role, prompting research into their potential therapeutic effect.

A new study in rats shows that exosomes appear to protect cells in the retina, the light-sensitive tissue in the back of the eye. Researchers investigated the role of stem cell exosomes on retinal ganglion cells, a type of retinal cell that forms the optic nerve that carries visual information from the eye to the brain. The death of retinal ganglion cells leads to vision loss in glaucoma and other optic neuropathies. Stem cells have been the focus of therapeutic attempts to replace or repair tissues because of their ability to morph into any type of cell in the body. However, from a practical standpoint, using exosomes isolated from stem cells presents some key advantages over transplanting whole stem cells. Exosomes can be purified, stored and precisely dosed in ways that stem cells cannot.

Another important advantage of exosomes is they lack the risks associated with transplanting live stem cells into the eye, which can potentially lead to complications such as immune rejection and unwanted cell growth. In a rat glaucoma model, researchers studied the effects of exosomes isolated from bone marrow stem cells on retinal ganglion cells. Exosomes were injected weekly into the rats' vitreous, the fluid within the center of the eye. Prior to injection, the exosomes were fluorescently labelled allowing the researchers to track the delivery of the exosome cargo into the retinal ganglion cells. Exosome-treated rats lost about a third of their retinal ganglion cells following optic nerve injury, compared with a 90-percent loss among untreated rats. Stem cell exosome-treated retinal ganglion cells also maintained function, according to electroretinography, which measures electrical activity of retinal cells. The researchers determined that the protective effects of exosomes are mediated by microRNA, molecules that interfere with or silence gene expression. Further research is needed to understand more about the specific contents of the exosomes.


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