MicroRNA and Protein Cargos of Human Limbal Epithelial Cell-Derived Exosomes and Their Regulatory Roles in Limbal Stromal Cells of Diabetic and Non-Diabetic Corneas
Nagendra Verma,
Drirh Khare,
Adam J. Poe,
Cynthia Amador,
Sean Ghiam,
Andrew Fealy,
Shaghaiegh Ebrahimi,
Odelia Shadrokh,
Xue-Ying Song,
Chintda Santiskulvong,
Mitra Mastali,
Sarah Parker,
Aleksandr Stotland,
Jennifer E. Van Eyk,
Alexander V. Ljubimov,
Mehrnoosh Saghizadeh
Affiliations
Nagendra Verma
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Drirh Khare
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Adam J. Poe
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Cynthia Amador
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Sean Ghiam
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Andrew Fealy
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Shaghaiegh Ebrahimi
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Odelia Shadrokh
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Xue-Ying Song
Genomics Core, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Chintda Santiskulvong
Genomics Core, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Mitra Mastali
Advanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Sarah Parker
Advanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Aleksandr Stotland
Advanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Jennifer E. Van Eyk
Advanced Clinical Biosystems Research Institute, The Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
Alexander V. Ljubimov
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Mehrnoosh Saghizadeh
Eye Program, Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, AHSP-A8104, Los Angeles, CA 90048, USA
Epithelial and stromal/mesenchymal limbal stem cells contribute to corneal homeostasis and cell renewal. Extracellular vesicles (EVs), including exosomes (Exos), can be paracrine mediators of intercellular communication. Previously, we described cargos and regulatory roles of limbal stromal cell (LSC)-derived Exos in non-diabetic (N) and diabetic (DM) limbal epithelial cells (LECs). Presently, we quantify the miRNA and proteome profiles of human LEC-derived Exos and their regulatory roles in N- and DM-LSC. We revealed some miRNA and protein differences in DM vs. N-LEC-derived Exos’ cargos, including proteins involved in Exo biogenesis and packaging that may affect Exo production and ultimately cellular crosstalk and corneal function. Treatment by N-Exos, but not by DM-Exos, enhanced wound healing in cultured N-LSCs and increased proliferation rates in N and DM LSCs vs. corresponding untreated (control) cells. N-Exos-treated LSCs reduced the keratocyte markers ALDH3A1 and lumican and increased the MSC markers CD73, CD90, and CD105 vs. control LSCs. These being opposite to the changes quantified in wounded LSCs. Overall, N-LEC Exos have a more pronounced effect on LSC wound healing, proliferation, and stem cell marker expression than DM-LEC Exos. This suggests that regulatory miRNA and protein cargo differences in DM- vs. N-LEC-derived Exos could contribute to the disease state.
