Chinese scientists have invented a new type of "protective agent" that can revive brain tissue that has been frozen for 18 months!

Friends who have read the novel "The Three-Body Problem" may still remember the plot in which a frozen human brain was sent to space and then revived, and even cloned into a complete body. Recently, a research team led by Dr. Shao Zhicheng from the Institute of Brain Science Translational Research at Fudan University published a new technology for cryopreservation of brain tissue in the journal "Cell Reports Methods", which successfully revived brain cells that had been frozen for up to 18 months. Will the technology in the novel be realized in reality?

Under normal circumstances, human cells are constantly metabolizing and renewing. Most enzymes that catalyze various biochemical reactions are most active in an environment close to normal body temperature. Therefore, when the temperature drops, the life activities of cells become slow. At extremely low temperatures, such as liquid nitrogen at about minus 196°C, the metabolism and death process of cells is almost completely suspended, and the state is preserved. Cryopreservation technology is of great significance to assisted reproduction, organ transplantation, disease research, drug development, etc.

Creating a cryogenic environment is easy, but the freezing and thawing process can cause fatal damage to cells.

Cells contain a lot of water. Once frozen, the volume of water will expand and form sharp ice crystals, which will "burst" the cells. In daily life, frozen meat and fruits are always soft and limp, precisely because the cells are damaged by ice crystals.

Therefore, a type of substance called cryoprotectant is used during freezing, and common ones include glycerol, sucrose, dimethyl sulfoxide, etc. Their freezing points are relatively low, and using them to replace the water in the cells before freezing can reduce the formation of ice crystals. The structure and function of reproductive cells are relatively simple, and the water content is relatively low. At present, the technology for freezing and preserving sperm and eggs is relatively mature.

Living human brain tissue with pathological characteristics is a reliable model for studying neurological diseases. However, it is not easy to obtain samples, and the cryopreservation effect is not ideal. Brain cells contain up to 80% water and are very sensitive to low-temperature damage. In addition, the functional structure of brain tissue is complex, and traditional technology cannot preserve most functional neurons.

Researchers have tried to conduct research using "brain-like organs" differentiated from embryonic stem cells. These brain-like organs are only a few millimeters in diameter, but can develop a variety of cell types and three-dimensional structures similar to the human brain. However, the high cost of long-term cultivation of brain-like organs limits their application. For the above reasons, animal models are still mainly used in drug testing, which has also led to the failure of more than 90% of candidate new drugs in clinical trials. Therefore, it is very necessary to establish a technology that can effectively cryopreserve brain-like organs and real brain tissue.

The research team of Fudan University used 9 cryoprotectants as alternatives to cryoprotect cortical brain organoids. Through multiple experiments, they found that a combination of dimethyl sulfoxide, methylcellulose, ethylene glycol and a cell apoptosis inhibitor (Y27632) had the best effect, and named this new protective agent "MEDY".

For cortical organoids with a culture period ranging from 28 days to more than 100 days, MEDY achieved good protection effects in terms of cell structure and neuronal growth activity. For organoids frozen for up to 18 months, neurons and proliferative progenitor cells were also ideally preserved, and the proliferation activity after thawing was close to that of unfrozen cells. MEDY is also applicable to organoids from other brain regions, such as spinal cord organoids, which also has potential for subsequent neural transplantation treatments for spinal cord injuries. In addition, the researchers also collected samples with a diameter of about 3 mm from the brain tissue of a 9-month-old child with epilepsy for testing. The results showed that the brain tissue was structurally intact after thawing and remained active in the culture medium for two weeks.

From brain organoids to brain tissues of real patients, MEDY shows good versatility. Cryopreserved models can be better used for the study of neurological diseases, drug screening, and the promotion of clinical treatment using neural brain organoids in the field of regenerative medicine. The current results are still based on micro-tissues of several millimeters, and in-depth research on more types and larger volumes of samples will be needed in the future. Although there is still a long way to go to achieve the goal of freezing the entire brain or even the entire human body in science fiction scenes, this is undoubtedly an important step forward for us.

This article is a work supported by the Science Popularization China Creation Cultivation Program

Author: Xu Sijia

Reviewer: Li Chong

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.