Endogenous epithelial progenitor cell injection has potential to repair the lacrimal gland

Mouse study from Scripps Research Institute (San Diego, CA, USA) suggests that injection of endogenous epithelial progenitor cells may initiate regenerative lacrimal gland repair for treatment of aqueous-deficiency dry eye and corneal disease.

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Aug 24, 2016

Researchers from the Scripps Research Institute (San Diego, CA, USA) have investigated the therapeutic potential of injected epithelial progenitor cells in regards to regenerating damaged or inflamed lacrimal glands. In a mouse model of human Sjögren's syndrome, the cell therapy improved functional recovery of the lacrimal gland, indicating it may be a potential avenue of treatment for human lacrimal gland chronic inflammation, and therefore diseases such as aqueous-deficiency dry eye.

The injection of endogenous lacrimal gland epithelial cell progenitors (ECPCs) in rodent models of Sjogren’s syndrome, an autoimmune disease that results in ADDE, resulted in long-term engraftment, with the cells developing into acinar and ductal compartments. The lacrimal gland displayed decreased cell infiltration, appropriate differentiation of the injected cells and improved structural integrity and function, demonstrating it as a potential treatment avenue for humans afflicted with lacrimal gland dysfunction.

When injured, a healthy lacrimal gland has the ability to regenerate in approximately 7 days; however when in a state of disease the regenerative capacity ceases to function. As the lacrimal gland is the primary contributor to the aqueous layer of the tear film, inadequate quantities or quality may result in aqueous-deficiency dry eye.

The study, recently published in Stem Cells Translational Medicine, utilized rodent models of autoimmune disease Sjögren’s syndrome, in particular older female mice as they correspond with the most commonly afflicted demographic in humans, and injected EPCPs into the lobes that form the lacrimal gland. Helen Makarenkova, who led the study, commented: “this is the first step in developing future therapies for the lacrimal gland”.

The EPCPs were selected due to epithelial tissue being a key component of lacrimal glands; however the team encountered a roadblock in separating epithelial cell progenitors without destroying them. “We had to figure out how to dissociate the tissue into single cells without completely obliterating everything,” commented Anastasia Gromova, the study’s first author. The team solved the challenge by labeling cells of interest with markers and utilizing various enzymes and reagents to draw them out of tissues.

After the injection of EPCPs the treated mice demonstrated a significant increase in tear production, suggesting that EPCPs could be utilized to mediate functional recovery of lacrimal glands, with further study indicating this was achieved by restoring the connection between myoepithelial contractile and secretory cells.

As part of the overall aim of helping this approach reach patients, the team next plan to research the duration in improvement of lacrimal glands after EPCP injections, to see if the benefit is long-term.

Sources: Gromova A, Voronov DA, Yoshida M et al. Lacrimal gland repair using progenitor cells. Stem Cells Transl. Med. doi:10.5966/sctm.2016-0191 (2016) (Epub ahead of print); http://www.scripps.edu/news/press/2016/20160818makarenkova.html

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