Transplantation of bFGF-expressing neural stem cells promotes cell migration and functional recovery in rat brain after transient ischemic stroke

Abstract

Cerebrovascular disease such as stroke is one of the most common diseases in the aging population, and neural stem cells (NSCs) transplantation may provide an alternative therapy for cerebral ischemia. However, a hostile microenvironment in the ischemic brain offers is challenging for the survival of the transplanted cells. Considering the neuroprotective role of basic fibroblast growth factor (bFGF), the present study investigated whether bFGF gene-modified NSCs could improve the neurological function deficit after transient middle cerebral artery occlusion (MCAO) in adult male Sprague–Dawley rats. These rats were intravenously injected with modified NSCs (5×106/200 μL) or vehicle 24 h after MCAO. Histological analysis was performed on days 7 and 28 after tMCAO. The survival, migration, proliferation, and differentiation of the transplanted modified C17.2 cells in the brain were improved. In addition, the intravenous infusion of NSCs and bFGF gene-modified C17.2 cells improved the functional recovery as compared to the control. Furthermore, bFGF promoted the C17.2 cell growth, survival, and differentiation into mature neurons within the infarct region. These data suggested that bFGF gene-modified NSCs have the potential to be a therapeutic agent in brain ischemia.

Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries

“…Human basic fibroblast growth factor (bFGF), as a member of FGF family, is a critical neurotrophic factor that can promote cell proliferation, suppress apoptosis, and maintain stemness of MSCs in vitro [ 43 ]. Furthermore, bFGF has also been confirmed to enhance the proliferation and differentiation of endogenous neural progenitor cells [ 44 ]. Our previous studies have shown that bFGF accelerated the DPSCs proliferation and survival in vitro and combination of DPSCs with bFGF exhibited a much better neuronal regeneration than bFGF or DPSCs alone in repairing the central nerve injuries [ 45 ].…”

Distinctive effect of anesthetics on the effect of limb remote ischemic postconditioning following ischemic stroke

“…This raises the question of why we were not able to see similar disparities in functional and anatomical outcomes. It has been observed in various preclinical and clinical studies that often functional outcomes are not fully translated into anatomical betterment or vice versa [39,40]; however, molecular or physiologic events responsible for such discrepancies remain elusive. Based on such findings where there is a missmatch between functional and anatomical outcomes, recent attention has focused on improving the quality of life after stroke.…”

Neural stem cell therapy for subacute and chronic ischemic stroke

“…In addition to angiogenesis, studies indicate that transplantation of NSCs in the early stroke phase may benefit long-term recovery through functional neuronal replacement, either directly or through augmentation of the endogenous neurogenic response [ 70 , 214 – 222 ]. For instance, implantation of exogenous human fetal NSCs into the ipsilateral striatum 48 h after MCAO in rats resulted in subpopulations of engrafted cells that differentiated to neuroblasts and mature neurons at 6 and 14 weeks in addition to increased amounts of proliferating and migrating neuroblasts from the SVZ [ 216 ].…”

“…Transplanted hNSCs also give rise to astrocytes in the rodent brain following transient forebrain ischemia [ 214 , 219 , 220 ] and intracranial hemorrhage [ 221 ]. Transplantation of mouse NSCs into the ipsilateral striatum of rats 24 h after MCAO also augmented endogenous neurogenesis and reduced infarct volume [ 215 , 222 ]. Of note, even though limited cell replacement has been observed in studies, a considerable amount of time is required for NSCs to differentiate into functional neurons, and there is still not enough evidence that cell replacement is vital for NSC-mediated recovery.…”