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Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel

ABSTRACT: Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel

PROVIDER: PRJNA862964 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20678287_1.fastq.gz	Fastqsanger.gz
	SRR20678287_2.fastq.gz	Fastqsanger.gz
	SRR20678288_1.fastq.gz	Fastqsanger.gz
	SRR20678288_2.fastq.gz	Fastqsanger.gz
	SRR20678289_1.fastq.gz	Fastqsanger.gz

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Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel

Project description:To investigate the timing of endogenous regenerative events in response to a single 10 Gy dose of IR, we sequeced the transcriptomes of glands from adult (6-7 wks)mice and 7- and 14-days post-IR. We then compared to the radiated glands to Non-IR (no radiation) controls, and performed differential expression analysis.

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Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel.

Project description: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 that 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 after radiation, with extensive acinar cell degeneration, dysfunction, and cholinergic denervation occurring thereafter. However, we found 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 nonirradiated levels over the long term (>3 months). Thus, we reveal a previously unknown regenerative approach for restoring epithelial organ structure and function that has extensive implications for human patients.

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Project description:Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland.

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