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Stephen Swioklo, Alex J Shortt, Che John Connon; Alginate-encapsulated adipose-derived stem cells: a storable solution for the delivery of therapeutic proteins to the ocular surface. Invest. Ophthalmol. Vis. Sci. 2017;58(8):139.
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Mesenchymal stem cells (MSCs) have shown considerable promise for promoting ocular surface regeneration after wounding or disease. This is mediated by the cocktail of therapeutic proteins MSCs produce at the site of injury. Encapsulation of MSCs within alginate is an effective method to preserve cells during liquid storage and has a proven record for cell implantation and bioactive delivery. Combining these strengths, we have investigated alginate-encapsulated MSCs as a “storable stem cell bandage” for precise therapeutic protein delivery to the ocular surface.
Human adipose-derived stem cells (hASCs), MSCs derived from fat, were encapsulated in calcium alginate and stored at hypothermic conditions (4-21°C) for 3 days before assessing cell viability and function. The effect of encapsulation and storage on the gene expression and production of proteins relevant to ocular surface repair was investigated. Optimal gel conditions were used for the storage, transport, and delivery of encapsulated hASCs to the ocular surface of mice with complete epithelial debridement. Corneal regeneration and opacity was assessed over 7 days.
Alginate-encapsulation had a significant cytoprotective effect, yielding a viable cell recovery of 86±6% following storage for 3 days. Moreover, cell function and phenotype were preserved. Encapsulation of hASCs within alginate had a dramatic effect on levels of secreted growth factors in culture. Importantly, hepatocyte growth factor (HGF) was considerably upregulated, both at the gene and protein level (20±5- and 13±7-fold of adherent controls respectively; p = < 0.05; n = 3). These changes were also apparent when encapsulated cells were stored for 3 days prior to culture. Mice treated with 3-day stored alginate-encapsulated hASCs exhibited improved corneal regeneration and reduced haze.
Alginate-encapsulation is suitable for preserving and delivering hASCs to the ocular surface as a “storable stem cell bandage”. Improvements in ocular regeneration in mice with debrided corneas may be aided by the differential regulation of growth factors, with increased HGF levels promoting re-epithelialization whilst attenuating scarring.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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