Greater understanding of the molecular regulation of DNA passed in extracellular vesicles from the mother's endometrium [womb lining] to the implanting embryo influences the embryo's metabolic rate and bioenergetics
Read the original research article here
Image adapted from work by David Bolumar and Javier Moncayo-Arlandi, and colleagues
Ingenomix Foundation and Carlos Simon Foundation, INCLIVA Health Research Institute, Valencia, Spain
Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
Published in eLife, December 2023
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How cancer vesicles breach the blood-brain barrier
Researchers discovered how small particles from cancer cells called extracellular vesicles cross the blood-brain barrier to make the brain more hospitable to metastatic tumors.
A detailed understanding of this process could guide strategies to stop brain metastases as well as methods to deliver drugs to the brain.
PHOTO: White arrows point to extracellular vesicles coming off a cell.
A new way to deliver multiple sclerosis drugs to the brain
Two researchers in the department of anatomy and cell biology in the UIC College of Medicine have received a seed grant to develop a new drug delivery method that holds promise in the treatment of multiple sclerosis.
Ernesto Bongarzone and Maria Givogri are one of only about a dozen research groups in the nation to receive a Dr. Ralph and Marian Falk Medical Research Trust Awards Programs 2017 Catalyst Award. U.S. Trust, Bank of America, N.A., serves as Trustee for the Falk Medical Research Trust. The $300,000, one-year award is for conducting preliminary research projects deemed high risk, but also high reward. The Catalyst Awards are a stepping stone to eligibility for the Falk Transformational Awards Program which provides $1,000,000 for a two-year funding cycle to successful Catalyst awardees to continue their work developing new ways to treat disease.
Bongarzone and Givogri are interested in turning naturally occurring extracellular vesicles – tiny “bubbles” given off by a range of cell types – into targeted delivery vehicles for drugs to treat multiple sclerosis.
“Extracellular vesicles are secreted by lots of cells, and they closely reflect the identity of the cell from which they came,” said Bongarzone, who is a professor of anatomy and cell biology at UIC. “If we can manipulate these vesicles to fuse with a specific cell type and carry a therapeutic agent or drug, they can be a powerful weapon against a variety of diseases.”
Extracellular vesicles are one of many ways cells communicate with each other — especially with distant cells. Materials including proteins, molecules and bits of RNA can be packaged into the vesicles, which travel in the bloodstream, cerebrospinal fluid and extracellular fluids until they fuse with their target cell and dump their cargo. But their contents may not always be benign, explained Givogri, who is research assistant professor of anatomy and cell biology at UIC. “They may play a significant role in spreading disease as well,” she said. “There is much more to learn about how they function in this way, including their role in cancer metastasis.”
Bongarzone and Givogri will use the award to test methods to optimize the production of extracellular vesicles from mesenchymal stem cells and tag them with receptors that will allow the vesicles to bind to specialized cells in the brain and spinal cord. These cells, called oligodendrocytes, are responsible for producing the insulating myelin sheath that surrounds nerve cells. In multiple sclerosis, oligodendrocytes do not produce enough myelin, and nerve impulses become disrupted leading to muscle weakness, pain and vision problems, among other symptoms.
“Mesenchymal stem cells are already prolific producers of extracellular vesicles,” Givogri explained.
Once the researchers can reliably produce extracellular vesicles that bind specifically to oligodendrocytes and test their safety and activity in mice, they will apply for further funding to help them incorporate a small molecule of RNA, known as micro RNA, that has been shown to help boost the production of myelin in oligodendrocytes.
“Using extracellular vesicles lets us send drugs across the blood-brain barrier, which many other therapeutic agents cannot cross,” said Bongarzone. “Another benefit is that we can take mesenchymal stem cells from a patient and use them to generate vesicles for drug delivery, which will remove issues of rejection.”
Chlamydia, gonorrhoea and syphilis; the top three sexually transmitted infections worldwide. What's at number 4? Trichomoniasis. It's caused by the parasite Trichomonas vaginalis, which sticks to cells lining the vagina or the urine-carrying duct in the penis. Different strains can infect the same body. Researchers now investigate how these strains communicate with each other by infecting human cells in a dish. Scanning electron microscopy of parasites (pictured, blue) revealed that different strains — some that stick well to cells (CDC1132) and some that are less sticky (G3) — communicate with each other by sending out tube-like protrusions (orange) of their cell membrane. This is facilitated by membrane packages (extracellular vesicles) released by the parasites. Analysing these vesicles revealed that they contain proteins involved in signalling and communication. Importantly, they found CDC1132 and G3 strains both become stickier in the presence of other strains. This may have implications for how trichomoniasis infection progresses.
Written by Lux Fatimathas
Image from work by Nehuén Salas and colleagues
Laboratorio de Parásitos Anaerobios, Instituto Tecnológico de Chascomús, Buenos Aires, Argentina
Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
Published in eLife, May 2023
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Much like we head to the Post Office and send a parcel to a friend, cells can send precious cargo between themselves too. These informational sacs called extracellular vesicles (EVs) are important in healthy bodies, but also play a role in disease. Now researchers have shown that EVs released by tumour cells could be another way by which cancers spread. The team showed that EVs shed by tumour cells contain DNA (green) and an enzyme called cGAS (red) known to be crucial for tumour progression. They also demonstrated that EVs from tumour cells and their cargo are transferred to recipient cells. Adding EVs containing the DNA sequence of a specific gene not normally found in mammary cells, to mammary cells growing in a dish, resulted in that ‘foreign’ gene being expressed. Understanding how cancer cells package and send precious cargo could be used to detect cancer sooner or provide new therapeutics in the future.
Written by Sophie Arthur
Image from work by James W. Clancy and colleagues
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
Image originally published with a Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
Published in Cell Reports, March 2022
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A team of researchers have discovered that a particle found in the blood of the young could be the secret to keeping older folks youthful.
“A team of researchers — who definitely aren’t vampires — have discovered new evidence that the blood of the young could be the secret to actually staying young.
In a new study published in the prestigious journal Nature Aging, the team found that particles in mouse blood called extracellular vesicles (EV) send instructions for a longevity protein called “Klotho” to muscle cells, according to a press release from the University of Pittsburgh. As the mice age, the EVs seemingly become weaker and send fewer instructions for the protein as a result.
However, when the team gave older mice the blood of younger mice, their cells and tissue began to take on more youthful features like enhanced muscle regeneration. When the EVs were removed from the blood, though, the effect faded.
In other words, it sounds a bit like the vampires of folklore, with the blood of the youthful sustaining the aged.”
Broken bones take time to mend but research has shown that they heal faster when there's accompanying brain damage. Scientists studying this conundrum uncovered a surprising method of crosstalk between the brain and the skeleton: damaged nerve cells release tiny balls, called small extracellular vesicles (sEVs), which travel through the bloodstream to the bones. The image shows the concentration of sEV’s, ranging from low (blue) to high (red), in the skull, long bones and vital organs at the bottom. Left and middle are samples from untreated controls. The sample on the right was infused with sEV’s from damaged brain cells and has red patches in the long bones where the balls have accumulated. Analysis of the sEV’s cargo revealed they contain biochemicals which stimulate bone growth and so accelerate healing. Since they can be assembled in the lab they have potential as a treatment to hasten fracture repair.
Written by Julie Webb
Image from work by Wei Xia, Jing Xie and Zhi-Qing Cai
Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
Published in Nature Communications, October 2021
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Circulating factors play an important role in tissue aging. Here, the authors show that serum EV subpopulations and cargoes remodel with age and that EVs from young mouse serum rejuvenate aged skeletal muscle.
Abstract
Heterochronic blood exchange (HBE) has demonstrated that circulating factors restore youthful features to aged tissues. However, the systemic mediators of those rejuvenating effects remain poorly defined. We show here that the beneficial effect of young blood on aged muscle regeneration was diminished when serum was depleted of extracellular vesicles (EVs). Whereas EVs from young animals rejuvenate aged cell bioenergetics and skeletal muscle regeneration, aging shifts EV subpopulation heterogeneity and compromises downstream benefits on recipient cells. Machine learning classifiers revealed that aging shifts the nucleic acid, but not protein, fingerprint of circulating EVs. Alterations in subpopulation heterogeneity were accompanied by declines in transcript levels of the prolongevity protein α-Klotho (Klotho), and injection of EVs improved muscle regeneration in a Klotho mRNA-dependent manner. These studies demonstrate that EVs play a key role in the rejuvenating effects of HBE and that Klotho transcripts within EVs phenocopy the effects of young serum on aged skeletal muscle.
