Improvement of deficits by transplantation of lentiviral vector-modified human amniotic mesenchymal cells after cerebral ischemia in rats

Abstract

Amniotic membrane is known to have the ability to transdifferentiate into multiple organs and is expected to stimulate a reduced immunologic reaction. Human amniotic membrane-derived mesenchymal stem cells (hAMCs) do not express the major histocompatibility complex (MHC) class I molecule and may be expected to show immunologic tolerance. A good deal of research has explored the clinical therapeutic potential of hAMCs. In the present study, we isolated hAMCs and transfected them with the brain derived neurotrophic factor (BDNF) gene using lentiviral vectors. These cells were then transplanted into the brains of rats subjected to a transient middle cerebral artery occlusion (MCAO). The hAMCs survived for three weeks in the brains of the ischemic rats, and some of the transplanted hAMCs expressed the neuronal marker MAP2 and the neuronal progenitor marker Nestin. Furthermore, caspase-3 activity and iNOS expression were decreased in the vicinity of the graft and injection site. Importantly, intracerebral grafting of EGFP-modified hAMCs and BDNF-transduced hAMCs significantly ameliorated behavioral dysfunction in ischemic rats. BDNF-hAMCs ameliorated the behavioral dysfunction of rats more rapidly and effectively relative to EGFP-hAMC-treated rats. Finally, the grafts also reduced the infarct volume. hAMCs survived in the brain tissue and improved functional recovery. Because of the lack of ethical concerns and the high supply of these cells, hAMCs represent a promising clinical treatment for gene delivery similar to stem cell strategies.