Scientists from the UCLA Jonsson Comprehensive Cancer Center have developed a simple, high-throughput method for transferring peripheral mitochondria and the associated mitochondrial DNA to mammalian cells. This approach enables researchers to design a key genetic component of cells, to treat and treat destructive diseases such as cancer, diabetes and metabolic disorders.
Study, published today in the journal Cell reports, describes how the new device developed by UCLA, called MitoPunch, moves mitochondria to 100,000 or more cells at the same time, which is a major improvement from the mitochondrial movement technologies that it is. The tool is part of the ongoing effort by UCLA scientists to understand mutations in mitochondrial DNA by developing controlled, therapeutic approaches that improve human cell function or model human mitochondrial diseases more closely. better.
The ability to generate cells with mitochondrial DNA sequences that are powerful for studying how genomes in the mitochondria and nuclei interact to regulate cell functions, which may be essential for understanding and potential treatment of diseases in patients. “
Alexander Sercel, Doctoral Candidate, David Geffen School of Medicine, UCLA and Co-author of the study
Mitochondria, often called a cell ‘powerplant’, are inherited from a person’s mother. They rely on the integrity of the mitochondrial DNA to perform their essential functions. Hereditary or inherited mutations of mitochondrial DNA can severely inhibit energy production and can cause destructive diseases.
Technologies for the treatment of mitochondrial DNA lag behind advances in the treatment of DNA in the cell cloud and have helped scientists to develop disease models and regenerative therapies for disorders caused by these mutations. Conventional procedures, however, are limited and complex, and for the most part can only deliver mitochondria with mitochondrial DNA sequences that are required in a limited number and mix of cells.
The MitoPunch device is simple to operate and allows consistent mitochondrial movements from a wide range of mitochondria separated from different donor cell types to many receiving cell types, even for non-human species, producing its enter cells that are isolated from mice.
“What sets MitoPunch apart from other technologies is the ability to innovate immortal, non-malignant cells, such as human skin cells, to generate a specific mitochondrial DNA-nuclear genome combination,” the co-author Alexander Patananan, UCLA postdoctoral. scholar, who now works at Amgen. “This advancement allowed us to investigate the effect of specific mitochondrial DNA sequences on cell functions by also enabling the reprogramming of those cells into stimulated stem cells that were then differentiated into working fat, cartilage, and bone cells. “
MitoPunch was created in the laboratory of Dr. Michael Teitell, director of the Jonsson Cancer Center and professor of pathology and laboratory pathology, Pei-Yu (Eric) Chiou, professor of mechanical and aerospace engineering at the School of Engineering and UCLA activist Henry Samueli. Science, and Ting-Hsiang Wu, of ImmunityBio, Inc., Culver City, CA.
MitoPunch builds on previous technology and a device called photothermal nanoblade, which the team developed in 2016. But unlike the photothermal nanoblade, which requires solemn lasers and optical systems to work, MitoPunch works by using pressure to move peripheral mitochondrial barrier through a porous cell-covered membrane. The researchers suggest that this activated pressure gradient creates the ability to puncture a cell membrane in separate locations, allowing the mitochondria to enter directly into receiving cells, and the then cell membrane repair.
“We knew when we first created the photothermal nanoblade that we needed to use a higher, simpler system that is more accessible for other labs to assemble and operate,” said Teitell, who also head of the department of pediatrics and developmental pathology and member of the UCLA Broad Cell Gas Research Center. “This new tool is highly efficient and will allow researchers to study the mitochondrial genome in a simple way – converting it from one cell to another – that can be used to determine the underlying biology. a discovery that regulates a wide range of cellular activities and may, one day, give hope for the treatment of mitochondrial DNA diseases. “
Source:
University of California – Los Angeles Health Sciences
Magazine Reference:
Patananan, AN, et al. (2020) A pressure-guided Mitochondrial movement pipeline generates mammalian cells of desirable genetic compounds and fares. Cell reports. doi.org/10.1016/j.celrep.2020.108562.