This paper was just released and shows the the improvement of lacrimal gland structure and function in adult mice.
This is another piece of positive data to show adult stem cells may help restore and repair damaged lacrimal glands in humans.
Sandra Lora Cremers, MD, FACS
The key points of this article:
1. Expression of Pax6 in Lacrimal Gland Epithelium (LGE) is required for Lacrimal Gland (LG) development,5
2. Barx2 plays an essential role in the progress of branching morphogenesis in LGE cells to form a 3D secretory gland structure.6
3. The aqueous fluid secreted from the acini of the LG through water channels such as aquaporin5 (AQP5) contains:
c. multiple proteins: which are key for wetness, lubrication, and antibiotic effects on the ocular surface.1, 7, 8
4. Autologous serum eye drops are used to supply tear proteins.13,14,15
5. Researchers have directly converted cell lineages from stem cells or fibroblasts to desired cell lineages using overexpression of a specific set of Transcription Factors for:
a. neural cells
b. myocardial cells
c. liver hepatocytes.22,23,24,25,26,27
6. Transcription Factors that are key are:
PAX6, FOXC1, and SIX1
7. My big question for Dr. Dartt and other researchers were embryonic stem cells used. They allude to using them but it is not clear in my first reading of the paper. If adult stem cells are safe and easy to use, and we can revert adult stem cells to the progenitor level, why even waste time and money (not to mention the moral issues many have with embryonic stem cells) on embryonic stem cells.
8. Another question: has anyone looked into how many “embryonic”/young baby stem cells are around the placenta: can researchers use these cells? Are they viable?
Lacrimal Gland Repair Using Progenitor Cells.
- Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA.
- Institute for Information Transmission Problems, Russian Academy of Sciences and A.N. Belozersky Institute of Physico-Chemical Biology of the Lomonosov Moscow State University, Moscow, Russia.
- Department of Clinical Pharmacology, Flinders University, Bedford Park, South Australia, Australia.
- Department of Ophthalmology Harvard Medical School, Schepens Eye Research Institute/Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film. Production of tears in insufficient quantity or of inadequate quality may lead to aqueous-deficiency dry eye (ADDE). Currently there is no cure for ADDE. The development of strategies to reliably isolate LG stem/progenitor cells from the LG tissue brings great promise for the design of cell replacement therapies for patients with ADDE. We analyzed the therapeutic potential of epithelial progenitor cells (EPCPs) isolated from adult wild-type mouse LGs by transplanting them into the LGs of TSP -1-/- mice, which represent a novel mouse model for ADDE. TSP-1-/- mice are normal at birth but progressively develop a chronic form of ocular surface disease, characterized by deterioration, inflammation, and secretory dysfunction of the lacrimal gland. Our study shows that, among c-kit-positive epithelial cell adhesion molecule (EpCAM+ ) populations sorted from mouse LGs, the c-kit+dim/EpCAM+ /Sca1 – /CD34 – /CD45 – cells have the hallmarks of an epithelial cell progenitor population. Isolated EPCPs express pluripotency factors and markers of the epithelial cell lineage Runx1 and EpCAM, and they form acini and ducts when grown in reaggregated three-dimensional cultures. Moreover, when transplanted into injured or “diseased” LGs, they engraft into acinar and ductal compartments. EPCP-injected TSP-1-/- LGs showed reduction of cell infiltration, differentiation of the donor EPCPs within secretory acini, and substantial improvement in LG structural integrity and function. This study provides the first evidence for the effective use of adult EPCP cell transplantation to rescue LG dysfunction in a model system. Stem Cells Translational Medicine 2017;6:88-98.