Medical Bulletin 11/ March/ 2024

Here are the top medical news for the day:

A new study reveals a new approach to treat infertility

A new research from Oregon Health & Science University showed the scientific basis of a promising methodology for treating infertility: transforming a skin cell into an egg capable of generating viable embryos.

The study, published in the journal Science Advances, documented the process of in vitro gametogenesis (IVG) in a mouse model, outlining the initial stages of a technique involving the transfer of a skin cell nucleus into a donated egg lacking its own nucleus. Through experimentation in mice, researchers induced the skin cell nucleus to halve its chromosomes, enabling fertilization by a sperm cell to produce a viable embryo.

“The goal is to produce eggs for patients who don’t have their own eggs,” said senior author Shoukhrat Mitalipov, Ph.D., director of the OHSU Center for Embryonic Cell and Gene Therapy.

Rather than attempting to differentiate induced pluripotent stem cells, or iPSCs, into sperm or egg cells, OHSU researchers focused on a technique based on somatic cell nuclear transfer, in which a skin cell nucleus is transplanted into a donor egg stripped of its nucleus.The method offers potential for women with advanced maternal age or those unable to produce viable eggs due to various reasons, including cancer treatment.

In the study, the researchers followed three steps: first, they transplanted the nucleus of a mouse skin cell into an egg devoid of its own nucleus.Next, stimulated by cytoplasm, the implanted nucleus shed half of its chromosomes, similar to the process of meiosis.This crucial step yields a haploid egg with a single set of chromosomes.Finally, the researchers fertilized the newly formed egg with sperm through in vitro fertilization, resulting in a diploid embryo with two sets of chromosomes, ensuring healthy offspring with balanced genetic contributions from both parents.

The findings revealed that the skin cell’s nucleus segregated its chromosomes each time it was implanted in the donor egg. In rare cases, this happened perfectly, with one from each pair of matching egg and sperm chromosomes.

“We’re skipping that whole step of cell reprogramming,” said co-author Paula Amato, M.D., professor of obstetrics and gynecology in the OHSU School of Medicine. “The advantage of our technique is that it avoids the long culture time it takes to reprogram the cell. Over several months, a lot of deleterious genetic and epigenetic changes can happen.”

“This gives us a lot of insight,” she said. “But there is still a lot of work that needs to be done to understand how these chromosomes pair and how they faithfully divide to actually reproduce what happens in nature.”

Reference: ALEKSEI MIKHALCHENKO, NURIA MARTI GUTIERREZ, DANIEL FRANA, ZAHRA SAFAEI, CRYSTAL VAN DYKEN, YING LI, HONG MA, AMY KOSKI, DAN LIANG, AND SHOUKHRAT MITALIPOV; Journal: Science Advances; DOI: 10.1126/sciadv.adk9001

Quality sleep enhances the functionality of the immune system

A team led by Professor Luciana Besedovsky from the Institute of Medical Psychology hasdemonstrated that sleep promotes the potential of immune cells – so-called T cells – to migrate toward lymph nodes.

Sleep increases the directed migration of T cells toward a signaling protein, the so-called ‘homing’ chemokine CCL19. This molecule mediates the migration of T cells, which possess the corresponding receptor for CCL19, to the lymph nodes, where the T cell immune defenses are ‘trained’ by being presented with antigens – for example, after a vaccination.

The research, published in the journal Brain, Behavior, and Immunity, showed that in people who slept after a vaccination, the immune response was twice as strong on average as in people who did not sleep during the night after the vaccination.

The scientists conducted multiple examinations on the concentration of different subgroups of T cells in the blood of a group of healthy individuals over two 24-hour periods. During one condition, participants slept for eight hours at night, while during the other, they stayed awake while resting in bed at night. Blood was then collected and analysed.

Analysis of the blood samples revealed significant differences between the test conditions: “Our results show that sleep promotes the migratory potential of various T-cell subpopulations,” saidBesedovsky.

Further experiments demonstrated that incubating T cells with plasma from sleeping participants similarly enhanced their migratory capabilities.“This demonstrates that soluble factors that are elevated in blood plasma during sleep mediate the effect of sleep on T-cell migration. So we can in a way recreate the effect of sleep in the lab using the blood plasma of sleeping persons,” reportedBesedovsky.

Scientists also identified growth hormone and prolactin as the decisive factors for this migration behavior. Both hormones showed sleep-dependent changes in concentration in the plasma, with higher values among the participants who slept during the night.

“Our results also have potential clinical implications. Thus, growth hormone and prolactin could be considered as new adjuvants to promote immune responses following vaccination, especially in aged people, who typically display reduced levels of these hormones during sleep.” concluded Besedovsky.

Reference: Estefanía Martínez-Albert, Nicolas D. Lutz, Robert Hübener, Stoyan Dimitrov, Tanja Lange, Jan Born, Luciana Besedovsky; Journal: Brain Behavior and Immunity; DOI: 10.1016/j.bbi.2024.02.021

Research reveals the mechanism by which estrogenprotects against fatty liver

New research from Karolinska Institute in Sweden revealed the protective role of estrogen against MASLD, a fatty liver disease that has surged amidst the ongoing obesity epidemic.

The findings, published in the Journal Molecular Systems Biology, showed how a new drug under development could become a future treatment for fatty liver disease and liver cancer.

The global obesity crisis has led to a sharp rise in fatty liver disease, where excess fat is stored in liver cells instead of fat cells. MASLD - metabolic dysfunction-associated steatotic liver disease- affects up to one in three adults. While MASLD can progress to severe conditions like cirrhosis and liver cancer, it majorly affects men.

“Women have a natural protection until menopause due to the female sex hormone oestrogen,” explained Claudia Kutter, senior researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska instituteand lead author of the study.

By genetically analyzing mice of both genders subjected to a high-fat diet, along with some male mice receiving estrogen, researchers pinpointed a crucial protein in fatty liver development. The protein, TEAD1, was discovered to regulate fat absorption in liver cells overall. Inhibiting TEAD1 shielded liver cells from detrimental fat buildup. Mice treated with estrogen exhibited reduced TEAD1 activity and less fat accumulation in the liver. Subsequent experiments blocking TEAD1 in human liver cells yielded similar outcomes.

“Since the activity of TEAD proteins is elevated in cancer, blocking TEAD at an early stage can also be positive from a cancer point of view,” said Kutter. “Patients suffering from liver cancer are currently diagnosed very late. If the patient is given this drug early in the process to protect against fatty liver, it can hopefully also prevent the development of liver cancer.”

“We want to focus on how to find the disease earlier and identifying new treatment targets. Different approaches may be needed for different patients depending on their gender and hormonal status.” concluded Kutter.

Reference: Christian Sommerauer, Carlos J Gallardo-Dodd, Christina Savva, Linnea Hases, Madeleine Birgersson, Rajitha Indukuri, Joanne X Shen, Pablo Carravilla, Keyi Geng, Jonas Nørskov Søndergaard, Clàudia Ferrer-Aumatell, Grégoire Mercier, Erdinc Sezgin, Marion Korach-André, Carl Petersson, Hannes Hagström, Volker M Lauschke, Amena Archer, Cecilia Williams, and Claudia Kutter; Journal: Molecular Systems Biology; DOI: 10.1038/s44320-024-00024-x