New UCLA-formed gadget moves mitochondria into at least 100,000 or more beneficiary cells

Overview

• Post By : Kumar Jeetendra


• Source: University of California - Los Angeles Health Sciences


• Date: 01 Jan,2021

Scientists from the UCLA Jonsson Comprehensive Cancer Center have developed a simple, high-throughput way of transferring isolated mitochondria and their associated mitochondrial DNA into mammalian cells. This approach enables researchers to tailor a key genetic component of cells, to study and potentially treat debilitating diseases such as cancer, diabetes and metabolic disorders.

A study, published today in the journal Cell Reports, describes how the new UCLA-developed device, known as MitoPunch, transfers mitochondria to 100,000 or more recipient cells simultaneously, which is a significant improvement from existing mitochondrial transfer technologies. The unit is part of the continued effort by UCLA scientists to comprehend mutations in mitochondrial DNA by developing controlled, manipulative approaches that enhance the function of human cells or model human mitochondrial diseases better.

Mitochondria, often known as the’powerplant’ of a mobile, are inherited from an individual’s mother. They rely on the integrity of the mitochondrial DNA to carry out their essential functions. Inherited or acquired mutations of the mitochondrial DNA can significantly impair energy production and can cause debilitating diseases.

Technologies for manipulating mitochondrial DNA lag behind improvements for manipulating DNA from the nucleus of a cell and might possibly help scientists develop disease models and regenerative therapies for disorders caused by these mutations. Latest approaches, however, are limited and complicated, and for the most part can only deliver mitochondria with desired mitochondrial DNA sequences into a limited number and variety of cells.

The MitoPunch device is simple to operate and allows for consistent mitochondrial transfers from a broad assortment of mitochondria isolated from various donor cell types into a multitude of receiver cell types, even for non-human species, such as for cells isolated from mice.

“What sets MitoPunch apart from other technology is the ability to engineer non-immortal, non-malignant cells, such as human skin cells, to create unique mitochondrial DNA-nuclear genome combinations,” said co-first writer Alexander Patananan, a UCLA postdoctoral scholar, who now works at Amgen. “This progress enabled us to study the effect of certain mitochondrial DNA sequences on cell works by also enabling the reprogramming of these cells to induced pluripotent stem cells that were then differentiated into functioning cartilage, fat, and bone cells.”

The ability to generate cells with desired mitochondrial DNA sequences is powerful for studying how genomes in the mitochondria and nucleus interact to regulate cell functions, which can be critical for understanding and potentially treating diseases in patients.”

Alexander Sercel, Doctoral Candidate, David Geffen School of Medicine, UCLA and Study’s Co-First Author

MitoPunch Was Made in the labs of Dr. Michael Teitell, director of the Jonsson Cancer Center and professor of pathology and laboratory medicine, Pei-Yu (Eric) Chiou, professor of mechanical and aerospace engineering in the UCLA Henry Samueli School of Engineering and Applied Science, and Ting-Hsiang Wu, from ImmunityBio, Inc., Culver City, CA.

MitoPunch builds upon prior technology and a device known as a photothermal nanoblade, which the group developed in 2016. The researchers suggest that this applied pressure gradient creates the ability to puncture cell membranes at different locations, allowing the mitochondria direct entry to recipient cells, followed by cell membrane repair.

“We knew when we first created the photothermal nanoblade which we would require a higher-throughput, simpler to use system which is more accessible for other labs to assemble and function,” said Teitell, who is also the chief of the division of pediatric and developmental pathology and a member of the UCLA Broad Stem Cell Research Center. “This new device is extremely efficient and allows researchers to study the mitochondrial genome in a very simple way — swapping it from one cell into another — that is used to uncover the fundamental biology that governs a broad range of cell functions and could, one day, provide hope for treating mitochondrial DNA diseases.”