Scientists develop high-throughput mitochondria transfer device

Scientists at UCLA Johnson Comprehensive Cancer Center have developed a simple, high-throughput method to transplant isolated mitochondria and related mitochondrial DNA into secretory cells. This approach enables researchers to adapt to the main genetic component of cells, for the study and possible treatment of debilitating diseases such as cancer, diabetes and metabolic disorders.

A study published today in a journal Cell reports, Describes that a new UCLA-developed device, called a mitochondria, simultaneously transfers mitochondria into 100,000 or more recipient cells, a significant improvement over existing mitochondrial transfer techniques. The device is part of an ongoing effort by UCLA scientists to understand mutations in mitochondrial DNA, which will improve mitochondria by developing controlled, manipulative approaches that improve the function of human cells or improve human mitochondrial diseases.

“The ability to produce cells with the desired mitochondrial DNA sequence is powerful for studying how the genome in the mitochondria and nucleus interacts to control cell functions, to treat patients and to diagnose diseases,” said doctor candidate Alexander Cerse. Is. ” David Geffen School of Medicine at UCLA and first-author of the study.

Mitochondria, always referred to as the cell’s ‘powerplant’, are inherited from a person’s mother. They rely on the integrity of mitochondrial DNA to perform their essential functions. Hereditary or acquired mutations in mitochondrial DNA can significantly impair the production of rhizomes and lead to consequent diseases.

Technologies for mitochondrial DNA manipulation are lagging behind advances in DNA manipulation in cell structures and can help scientists develop disease models and regenerative therapies for disorders caused by these mutations. Current approaches, however, are limited and complex, and deliver mitochondria with the desired mitochondrial DNA sequence in a limited number and variety of cells in most parts.

The mitochondrial device is easy to operate and allows microcundrial transfer from large mitochondria to different mitochondria from different donor cell types, including human species, including cells from mice.

Alexander Patanan, co-author of UCOEL’s Postdoctoral, said, “What sets Mitopunch apart from other techniques is the ability to engineer non-immortal, non-lethal cells, such as human skin cells.” Scholar, who now works at Amgen. “This previously allowed us to study the effect of specific mitochondrial DNA sequences on cell functions. These cells were enabled to reprogram in induced pluripotent stem cells, which were then separated into functional fat, cartilage and bone cells.”

Mitopunch was formed by Joe Johnson Cancer Center Director and Professor of Pathology and Laboratory Medicine, Pei-U (Eric) Chio, UCLA Henry Sammy School of Engineering and Engineering and Applied Professor Dr. Michael. Was performed in Michael Tettle’s laboratories. Science by ImmunityBio, Inc., Culver City, CA, and Ting-Xiang Wu.

Mitopunch builds on a previous technology and a device called a photothermal nanoblade, which the team developed in 2016. But unlike photothermal nanoblades, which are required to operate sophisticated lasers and optical systems, the mitochondria work by using pressure to push the isolated mitochondrial suspension through the pores. Membrane coated with cells. Researchers have proposed that this applied pressure gradient, the ability to puncture cell membranes in specific locations, allows direct entry of mitochondria into recipient cells, after which cell membranes are repaired.

“When we first built photothermal nanoblades, we knew we would need a high-throughput, simpler system that would be more accessible to other laboratories to assemble and operate,” said Tiatel, who is also head of the pediatric department. Member of Developmental Pathology and UCLA Broad Stem Cell Research Center. “This new device is very efficient and allows researchers to easily study the mitochondrial genome – moving it from one cell to another – which could be used to uncover the basic biology that governs a wide range of cell functions, one day, mitochondrial DNA diseases.” Give hope for a cure. ”