Colvin Hedley proposes targeting mitochondria, the parts of cells that supply energy, to selected cells and using them as temporary signal carriers
Colvin Hedley proposes targeting mitochondria, the parts of cells that supply energy, to selected cells and using them as temporary signal carriers
In an interview published on August 23, immunologist Colvin Hedley described the next step in his mitochondrial transfer program. In a 2024 paper on which he was the first author, donor mitochondria altered measurable features of old immune cells. Hedley now proposes directing mitochondria to selected cells and determining in advance how long the carrier will remain in the body.
Mitochondria supply cells with energy and participate in cellular signaling. Hedley began with aging CD4+ T-cells, immune cells that initiate and coordinate the response to infection. As these cells age, they become less able to activate and divide. Impaired mitochondrial function may contribute to this change.
In a 2024 paper, the researchers mixed donor mitochondria from young skin cells with CD4+ T-cells from older donors and placed the mixture in a centrifuge, an instrument that spins samples rapidly, for five minutes. This procedure transferred the mitochondria into the T-cells. After stimulation, more cells entered an activated state and divided more actively. With prolonged stimulation, the researchers found fewer signs of cellular exhaustion and aging. In a mouse model of tuberculosis, they transplanted treated old T-cells and compared the composition of these cells and signs of their exhaustion during infection.
This procedure is suitable for cells that can be removed from the body. For delivery inside the body, Hedley proposes attaching an antibody to the outer mitochondrial membrane. An antibody is a protein that recognizes a receptor on the surface of a selected cell. This should direct the carrier to the intended cell. In the interview, Hedley showed a mitochondrion linked to an antibody targeting cells that line blood vessels, and he described a version designed for immune cells.
“If a mitochondrion can be configured, it might be possible to use it as a temporary carrier for reprogramming… because it is tagged for destruction, it does not remain for long.”
By “configured,” Hedley means selecting the quality and composition of the donor mitochondria, choosing an antibody for targeted delivery, and adding a tag for mitophagy, the process by which a cell destroys its own mitochondria. Under this hypothesis, the antibody connects the mitochondrion to the intended cell. The mitochondrion then delivers a brief signal, after which the cell breaks it down.
Whether a brief signal is sufficient to restore a large area of damaged tissue is the issue raised by Michael West in his partial reprogramming hypothesis. Both strategies require the signal to alter cellular function before the cell destroys the delivered mitochondrion.
Hedley conducted a pilot study in eight old marmosets, which are small monkeys. Six animals received weekly doses of mitochondria carrying an antibody that targeted them to immune cells for eight weeks. Two received saline. Blood and immune cells were collected every two weeks to track dosing and the immune response. This pilot moves the investigation from a test tube into living animals. Its purpose is to determine whether such a carrier can be dosed precisely and directed to immune cells.