RESUMEN
Peripheral nerve injuries occur as the result of sudden trauma and lead to reduced quality of life. The peripheral nervous system has an inherent capability to regenerate axons. However, peripheral nerve regeneration following injury is generally slow and incomplete that results in poor functional outcomes such as muscle atrophy. Although conventional surgical procedures for peripheral nerve injuries present many benefits, there are still several limitations including scarring, difficult accessibility to donor nerve, neuroma formation and a need to sacrifice the autologous nerve. For many years, other therapeutic approaches for peripheral nerve injuries have been explored, the most notable being the replacement of Schwann cells, the glial cells responsible for clearing out debris from the site of injury. Introducing cultured Schwann cells to the injured sites showed great benefits in promoting axonal regeneration and functional recovery. However, there are limited sources of Schwann cells for extraction and difficulties in culturing Schwann cells in vitro. Therefore, novel therapeutic avenues that offer maximum benefits for the treatment of peripheral nerve injuries should be investigated. This review focused on strategies using mesenchymal stem cells to promote peripheral nerve regeneration including exosomes of mesenchymal stem cells, nerve engineering using the nerve guidance conduits containing mesenchymal stem cells, and genetically engineered mesenchymal stem cells. We present the current progress of mesenchymal stem cell treatment of peripheral nerve injuries.
RESUMEN
Syntheses of racemic forms of the main secondary metabolites of Quararibea funebris, (+/-)-funebrine, (+/-)-funebral, and their biogenetic precursor (+/-)-(2S,3S,4R)-gamma-hydroxyalloisoluecine lactone have been developed. In synthetic studies, a new variation of the Paal-Knorr condensation employing titanium isopropoxide was utilized to construct the pyrrole lactone moiety. Two efficient synthetic approaches to the key (+/-)-gamma-amino lactone have been developed, one based on Claisen chemistry and the other on addition reactions to the butenolide ring of beta-angelicalactone. The restricted rotation around the C(sp(3))-N(sp(2)) bond in the pyrrole lactone structures of (+/-)-funebrine, (+/-)-funebral, and related aldehydes has been probed by conformational dynamic studies, and the barriers for interconversion between conformations have been measured by full NMR line-shape analysis. Molecular mechanics (MMX) and a (1)H-(1)H NOE study indicate a distinct preferred conformation for (+/-)-funebrine.