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Lacrimal Gland Repair Using Progenitor Cells.
- Source :
-
Stem cells translational medicine [Stem Cells Transl Med] 2017 Jan; Vol. 6 (1), pp. 88-98. Date of Electronic Publication: 2016 Aug 15. - Publication Year :
- 2017
-
Abstract
- 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 <superscript>-/-</superscript> mice, which represent a novel mouse model for ADDE. TSP-1 <superscript>-/-</superscript> 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 <superscript>+</superscript> ) populations sorted from mouse LGs, the c-kit <superscript>+</superscript> dim/EpCAM <superscript>+</superscript> /Sca1 <superscript>-</superscript> /CD34 <superscript>-</superscript> /CD45 <superscript>-</superscript> 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 <superscript>-/-</superscript> 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.<br /> (© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)
- Subjects :
- Animals
Cell Differentiation
Colony-Forming Units Assay
Epithelial Cell Adhesion Molecule metabolism
Epithelial Cells cytology
Mice, Inbred C57BL
Proto-Oncogene Proteins c-kit metabolism
Stem Cell Transplantation
Transcription Factors metabolism
Lacrimal Apparatus physiology
Regeneration
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2157-6564
- Volume :
- 6
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Stem cells translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28170196
- Full Text :
- https://doi.org/10.5966/sctm.2016-0191