RT Journal Article
SR Electronic
T1 Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.19.491203
DO 10.1101/2022.05.19.491203
A1 Jianlong Li
A1 Sonia Sudiwala
A1 Lionel Berthoin
A1 Alison J. May
A1 Seayar Mohabbat
A1 Hanan Sinada
A1 Eliza A. Gaylord
A1 Noel Cruz Pacheco
A1 Isabelle M.A. Lombaert
A1 Oju Jeon
A1 Eben Alsberg
A1 Chelsea S. Bahney
A1 Sarah M. Knox
YR 2022
UL http://biorxiv.org/content/early/2022/05/19/2022.05.19.491203.abstract
AB Salivary gland acinar cells are severely depleted after radiotherapy for head and neck cancer, leading to loss of saliva and extensive oro-digestive complications. With no regenerative therapies available, organ dysfunction is irreversible. Here using the adult murine system, we demonstrate radiation-damaged salivary glands can be functionally regenerated via sustained delivery of the neurogenic muscarinic receptor agonist, cevimeline. We show that endogenous gland repair coincides with increased nerve activity and acinar cell division that is limited to the first week post-radiation, with extensive acinar cell degeneration, dysfunction and cholinergic denervation occurring thereafter. However, we discovered that mimicking cholinergic muscarinic input via sustained local delivery of a cevimeline-alginate hydrogel was sufficient to regenerate innervated acini and retain physiological saliva secretion at non-irradiated levels over the long-term (> 3 months). Thus, we reveal a novel regenerative approach for restoring epithelial organ structure and function that has significant implications for human patients.Teaser Novel application of an injectable neurogenic-based hydrogel for restoring the structure and function of radiation-damaged tissue.Competing Interest StatementThe authors have declared no competing interest.