Joana Neves
Joana Neves is the 2019 grand prize winner of the Sartorius & Science Prize for Regenerative Medicine & Cell Therapy, for work that offers a promising approach to improve the outcome of regenerative stem cell-based therapies aimed at delaying age-related degenerative diseases.
Using the fruit fly Drosophila as a model organism, Neves discovered an evolutionarily conserved mechanism of tissue repair - immune modulation by the protein MANF - which she harnessed to restore visual function in old, blind mice with retinal disease. The findings identify and help to address a major challenge imposed by the natural aging process, which has limited the clinical application of regenerative medicine approaches to treat those most likely to suffer from chronic and often debilitating degenerative conditions - elderly patients.
One way to stave off the inevitable effects of aging is through novel regenerative stem cell-based therapies, which promise the ability to repair or rejuvenate aged or diseased tissues and organs using stem cells. These cells are the body's raw cellular resource and progenitors from which every specialized human cell is derived. Some can be guided into becoming specific cells that can be transplanted and used to repair tissues. However, while regenerative medicine is advancing quickly and therapies are increasingly rolling into clinical trials, Neves said the overall benefits for human health remain limited, particularly in the ill and elderly.
Aging and degenerative diseases are often associated with the loss of ability for many tissues to regenerate, in part because the patients often being treated have tissues lacking an intact repair response capable of sustaining the functional integration of the transplanted cells, said Neves. Because of this, developing truly successful regenerative therapies has remained challenging.
Neves identified this significant roadblock in her work to apply stem-cell based interventions to treat degenerative retinal disease in fruit flies and found it to be due to the inflammatory environment often present in aged and diseased tissues. Finding a way to resolve chronic inflammation and promote an environment supportive of repair could provide an efficient and effective way to make the outcome of stem cell-based therapies more successful.
"This work led to the identification of MANF as an immune modulatory molecule with pro-repair activity that exists in circulation in our bodies but lost as we age," said Neves. She discovered that the protein MANF is a critical part of a conserved biological process necessary for limiting age-related inflammation while promoting tissue maintenance in young organisms. Using MANF intervention alongside stem-cell based photoreceptor replacement therapies, she was able to greatly improve visual function in mice, highlighting the clinical utility of the approach. "This work is the proof of principle demonstration that immune modulatory interventions can be effective strategies to improve the success of regenerative therapies applied to aged and diseased organs," said Neves.