Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat

Abstract

Effects of neural stem cell and olfactory ensheathing cell cotransplants on tissue remodelling after transient focal cerebral ischemia in the adult rat. Neurochemical Research, 42(6), pp. 1599-1609.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/136264/ with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a sixty-minute middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging (MRI). Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.

Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks

“…Numerous experimental studies, including recent studies from our group, have demonstrated the potential of exogenously or endogenously derived stem cells alone or in combination with in situ tissue engineering strategies and/or pharmacotherapeutics in promoting transplant‐mediated repair with functional restoration through such diverse mechanisms as neuroprotection, cell replacement, remyelination, tissue/vascular remodelling and de novo neurogenesis (Augestad et al., ; Bible et al., ; Jendelová et al., ; Kokaia & Lindvall, ; Lindvall & Kokaia, ; Massensini et al., ; Medberry et al., ; Sandvig et al., ). Although highly promising and extremely valuable in elucidating relevant recovery mechanisms at the experimental level, clinical translation of such approaches tends to be confounded by significant challenges, such as allograft rejection as well as the intricacies inherent in trying to create safe, functional in situ biointerfaces that could effectively re‐establish functional connectivity in multiple foci (Sandvig et al., ).…”

Olfactory ensheathing cell transplantation improving cerebral infarction sequela: a case report and literature review

“…Generally, 80% stroke cases are ischemic stroke [15]. Ischemic events trigger complex molecular cascade reactions, including cell depolarization, excitotoxicity, impaired cellular energy metabolism, and disruption of the blood-brainbarrier [3]. Current treatments of ischemic stroke are limited to restore perfusion, promote circulation and protect cells from acute death [16].…”

“…In recent years, cell transplantations have been showed of great therapeutic potential in neurorestoration. A number of studies have demonstrated that olfactory ensheathing cells (OECs) function in secretory [3,4], tissue remodeling [5], tissue migration [6][7][8] and immune regulation [8,9], and are prominent in repairing various nervous system diseases. In particular, OECs have eminent ability to stimulate axonal repair, enhance plasticity and support axonal retention in the central nervous system (CNS) [10].…”

The insights into molecular pathways of hypoxia‐inducible factor in the brain

“…Reciprocally, NSC have been found as modulators of inflammation and tissue remodeling after several brain injuries, which might contribute to a feedback regulation loop in neurological diseases with neuroinflammatory component (Augestad et al, ). NSC may have a suppressive effect on inflammation via the inhibition of T‐cells (Einstein et al, ).…”