Cell-free matrix derived from adipose mesenchymal stromal cells enhances corneal rehabilitation via delivery of nerve regenerative PGRN

Abstract

Promotion of corneal dense network of nerve is a promising method to treat severe corneal injury, yet with limited effective drugs. In our previous work, decellularized matrix of adipose derived mesenchymal stromal cells (ADMSCs), named as DMA, presented excellent conjunctival repair capacity with proper suture resistance and immune modulatory characteristics. Thus, we intended to investigate their potential application in facilitating corneal repair after alkali burn. Owing to the transparent characteristic of DMA, DMA could be applied as novel ocular bandages with nutritious function. In this study we found that cornea treated with DMA showed accelerated recovery compared with those received amniotic membrane (AM) treatment by fluorescein staining, slip-lamp examination, OCT and corneal nerve immunostaining. Further, in order to find key components responsible for the faster recovery, high-throughput proteomic analyses were conducted and more than 2000 proteins, including associated signaling pathways, were identified in DMA. Intriguingly, progranulin (PGRN), one of enriched proteins identified in DMA, was firstly recognized for its neurotrophic role in alleviation of corneal damage. To sum up, DMA exhibited a potent clinical application with a cocktail of key therapeutic factors, in which PGRN was a crucial factor in promoting neurite outgrowth and re-establishing homeostasis of the cornea.