We humans may rule the jungle, but the plants around us do have us beat on one thing: photosynthesis, or the ability to convert sunlight into energy.
Now, scientists at China’s Zhejiang University School of Medicine have harnessed plant power in mammalian cells to get them to produce energy when exposed to light. In a study published Dec. 7 in Nature, they described how they built tiny photosynthetic plant organelles called thylakoids and transplanted them into mammalian cells. They then demonstrated that the cells could stall disease progression in mouse models of osteoarthritis.
“The possibility of using a plant photosynthetic system to specifically supply ATP and NADPH in mammalian cells in a light-dependent manner is an exciting achievement that opens up possibilities of metabolism engineering,” Francisco Cejudo, a University of Seville professor who was one of the peer reviewers for the publication, said in a research summary Nature provided.
Many diseases are driven by dysregulated cell metabolism, or the creation of energy for essential processes, like building proteins. The ability to deliver ATP and NADPH to cells to improve metabolism could have many clinical applications, but it’s difficult to do.
It makes sense to turn to thylakoids as a solution. Thylakoids are plants’ photosynthesis factories, converting sunlight into ATP and NADPH through a series of chemical reactions. Plant cells use this energy to synthesize proteins just as mammalian cells do.
To see whether thylakoids could indeed provide energy to cells from another species, the scientists used young spinach leaves to build nanosized structures called nanothylakoid units. When they cultured them with mammalian cells, they found that the units could enter the cells and produce ATP and NADPH when exposed to light.
They then sought to find out whether the units would be capable of alleviating disease. For this, the researchers chose to study osteoarthritis, a condition where inflammation causes deficits in cell energy metabolism that ultimately results in stiff, painful joints. They injected the knee joints of arthritic mice with mammalian cells containing the nanothylakoid units, then irradiated the injected joints with red light every three days for 30 minutes at a time. Eight and 12 weeks later, they conducted a batch of tests to see how the mice fared.
The mice that were implanted with the cells and treated with red light had lower levels of cartilage destruction than controls. This suggested that the treatment was stalling the disease.
While other researchers have created artificial cells with the ability to mimic thylakoids’ processes, this is the first time anyone has built thylakoids entirely from natural plant material, successfully transplanted them into another species and then seen them create energy that’s not only produced within host cells but is also abundant enough to have a biological effect.
To make it possible, the scientists had to figure out a way to keep the immune system from attacking the thylakoids. After an earlier strategy to remove “unwanted” material failed, they tried coating them in membranes from broken-down animal cells, allowing them to fly under the immune system’s radar. While the membranes of the cells injected into the mice came from chrondrocytes—cells that make up cartilage in joints—they demonstrated in cell culture experiments that it was possible to make membranes from other cell types, too.
“We think that this work demonstrates that even relatively limited artificial modification of natural biomaterials can achieve specific functions for various applications,” they wrote in the Nature research summary.
The scientists hope to conduct early-stage clinical trials to see whether their cells could work in humans with osteoarthritis. They also plan to conduct additional research to find a balance between optimal photosynthesis and any cell damage that could be caused by the formation of reactive oxygen species, a possible consequence of exposure to excess light.