Scientists at the UCLA Johnson Comprehensive Cancer Center have developed a simple, high-throughput method for transferring isolated mitochondria and their related mitochondrial DNA into mammalian cells. This method allows researchers to tailor the key genetic components of cells to study and possibly treat debilitating diseases such as cancer, diabetes and metabolic disorders.
A study published today in the journal Cell Report, Describes how the new UCLA device MitoPunch can transfer mitochondria to 1
“The ability to produce cells with the required mitochondrial DNA sequence is powerful for studying how the genomes in the mitochondria and the nucleus interact to regulate cell function, which is essential for understanding and potentially treating diseases in patients,” Alexander Sese Alexander Sercel said the David Geffen School of Medicine at UCLA is the first author of the study.
Mitochondria (often called the “power plant” of the cell) are inherited from a person’s mother. They rely on the integrity of mitochondrial DNA to perform their basic functions. Inheritance or acquired mutations in mitochondrial DNA can greatly impair energy production and may lead to debilitating diseases.
The technology of manipulating mitochondrial DNA lags behind the technological advancement of manipulating DNA in the nucleus, and may help scientists develop disease models and regenerative therapies for diseases caused by these mutations. However, current methods are limited and complicated, and in most cases can only deliver mitochondria with required mitochondrial DNA sequences to a limited number and types of cells.
The MitoPunch device is easy to operate. It can continuously transform mitochondria from various mitochondria isolated from different donor cell types into multiple recipient cells, even for non-human species (including cells isolated from mice). get on.
University of California, Los Angeles (UCLA) postdoctoral co-first author Alexander Patananan (Alexander Patananan) said: “What makes MitoPunch stand out from other technologies is the engineering of non-immortal, non-malignant cells such as human skin Mitochondrial DNA-nuclear genome capabilities.” Scholar, now working at Amgen. “This advancement allows us to study the effects of specific mitochondrial DNA sequences on cell function by reprogramming these cells into induced pluripotent stem cells and then differentiate into functional fat, cartilage and bone cells.”
MitoPunch was created in the laboratory of Dr. Michael Teitell, Director of Johnson Cancer Center and Professor of Pathology and Laboratory Medicine, and Pei-Yu (Eric) Chiou, Professor of Mechanical and Aerospace Engineering at the Henry Samuel School of Engineering and Applications at UCLA “Science” and Wu Tingxiang of ImmunityBio, Inc. of Culver City, California.
MitoPunch builds on previous technology and a device called photothermal nanoblade developed by the team in 2016. However, unlike the photothermal nanoblade that requires a complicated laser and optical system to operate, the working principle of MitoPunch is to use pressure to push the cell membrane of an isolated mitochondrial suspension through a hole. The researchers proposed that this applied pressure gradient can puncture the cell membrane at discrete locations, allowing mitochondria to directly enter the recipient cell and repair the cell membrane.
Teitell is also the head of the Pediatrics and Pediatrics Division. He said: “We knew when we first created the photothermal nanoblade that we needed a higher throughput and easier-to-use system. Other experiments The laboratory can make it easier to assemble and operate the system.” Developmental Pathology, a member of UCLA’s extensive stem cell research center. “This new device is very effective, allowing researchers to study the mitochondrial genome in a simple way-swapping it from one cell to another-which can be used to reveal the basic biology that controls a wide range of cellular functions, and could one day It provides hope for the treatment of mitochondrial DNA diseases.”
Cell surgery with laser-driven nanoblade
Alexander N. Patanan Cell Report (2020). DOI: 10.1016 / j.celrep.2020.108562
Provided by the University of California, Los Angeles
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