Prof. Eldad Tzahor at the Weizmann Institute of Science gazed into the microscope in his laboratory one day and saw a steak.
The miracle happened in the Department of Molecular Cell Biology as part of a study on muscle tissue regeneration. During an experiment in muscle stem cells led by postdoctoral researcher Dr. Tamar Eigler, the cells in the lab vessels fused into tiny fibers that thickened rapidly – and within a few hours well-developed muscle fibers formed that resembled a whole slice of meat.
The result led to found ProFuse Technology, a new startup that develops the findings for use in the food-tech industry.
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To decipher the chain of molecular events that led to the rapid and juicy transformation in the laboratory dish, Prof. Tzahor and Dr. Eigler teamed up with Dr. Uri Avinoam, whose laboratory specializes in the study of cell fusion.
In their study published today in the scientific journal Developmental Cell, the research team reveals a new molecular pathway responsible for the rapid formation of muscle fibers.
The new findings may advance both the study of muscle tissue regeneration in the body and the holy grail of the food industry today – efficient production of cultured meat that will replace the polluting meat industry.
The beginning of the molecular pathway, which ends as a steak in a dish, is in a small molecule that blocks the enzyme ERK in myoblasts. This blockage leads to the differentiation of the stem cells in the culture into muscle cells, the formation of tiny fibers, and the activation of the enzyme CaMKII, which in turn leads to a leap in the rate of fusion and growth of the fibers.
To test whether the molecular pathway detected in the laboratory is indeed involved in the regeneration process in muscle tissue in the body as well, Dr. Eigler created engineered mice without CaMKII – the enzyme that appears at the end of the pathway. The fact that the cultured blasts in a timed manner indicate the activation of a structured muscle-building program. In other words, it seems that the processes observed in the laboratory do indeed correspond to the way in which muscle fibers in the body coalesce.
Stem cells of muscle tissue called myoblasts are formed in the fetus, but a pinch of them is retained on the surface of the muscle fibers throughout our lives. Although the number of these decreases with age, when a muscle is injured – they are responsible for its repair and regeneration.
However, to begin the process of rehabilitation, they must stop dividing themselves, differentiate into muscle cells and reunite with each other and with the damaged muscle tissue. “Without fusion, there is no regeneration,” Dr. Eigler emphasizes. “Therefore the key to understanding the process of muscle tissue regeneration lies in the process of fusion of the myoblasts.”
There’s a historic Weizmann Institute angle to this research: One of the founding fathers of the study of muscle growth, the late Prof. David Yaffe, had been a Weizmann scientist.
The myoblast cultures that he developed in the 1960s for exploring the differentiation and fusion of these cells have for decades been used by scientists all over the world. Now, some sixty years later, the new, efficient way of inducing such differentiation and fusion discovered by Weizmann scientists may greatly advance future studies in the field.
