Immunomodulation- and angiogenesis-led peripheral nerve regeneration

Abstract

Excessive inflammation within damaged tissue usually leads to delayed and insufficient regeneration In peripheral nervous system where fully recovery doesn’t occur frequently modulating the inflammatory response to promote nerve regeneration has become more and more promising however there is a lack of practical therapeutic strategy for doing so Thrombomodulin (TM) is a transmembrane glycoprotein containing five domains Amount all the domains lectin-like domain of TM shows ability in suppressing inflammatory response In the current study we revealed the potential of TM in switching pro-inflammatory type1 macrophages (M1) to anti-inflammatory type2 macrophage (M2) by using THP1 cell We also evaluated the therapeutic effect of TM-enhanced M2 transition on transected sciatic nerve Our in vivo finding showed that TM treatment led to a better nerve regeneration and further preserved the effector muscle function Furthermore the supplementation of TM also exhibits a remark function in promoting axon elongation and remyelination through increasing the number of M2 Beside immunomodulation we also found that enhancing angiogenesis and creating a pro-angiogenetic microenvironment is critical for nerve regeneration In the current study we also evaluated the potential of endothelial lineage cell (ELC) –derived exosome in enhancing nerve recovery In comparison to adipose-derived stem cell (ASC) ELC exhibited higher expression of the angiogenetic microRNA (miR)-126 Correspondently the miR-126 was also enriched in ELC-derived exosomes We found the ELC conditional medium increased the number of outgrowing neurite in the DRG explants Concurrently ELC-exosome exhibited ability in promoting Schwann cell (SC) maturation Taken together the current study proved novel therapeutic strategies for peripheral nerve regeneration by immunomodulation and enhancing angiogenesis

Date of Award	2020
Original language	English
Supervisor	Chia-Ching Wu (Supervisor)