Resolution of Stroke Deficits Following Contralateral Grafts of Conditionally Immortal Neuroepithelial Stem Cells

Abstract

Background and Purpose-Grafts of MHP36 cells have previously been shown to reduce dysfunction after global ischemia in rats. To test their efficacy after focal ischemia, MHP36 cells were grafted 2 to 3 weeks after transient intraluminal middle cerebral artery occlusion (tMCAO) in rats. Methods-MHP36 cells were implanted into the hemisphere contralateral to the lesion, with 8 deposits of 3 L of cell suspension (25 000 cells per microliter). Sham grafted rats received equivalent volumes of vehicle. Three groups, sham-operated controls (nϭ11), MCAOϩsham grafts (nϭ10), and MCAOϩMHP36 grafts (nϭ11), were compared in 3 behavioral tests. Results-In the bilateral asymmetry test, MCAOϩMHP36 grafted rats exhibited neglect before grafting but subsequently showed no significant dysfunction, whereas MCAOϩsham grafted rats showed stable sensorimotor deficits over 18 weeks relative to controls. MCAOϩsham grafted rats demonstrated spontaneous motor asymmetry and increased rotational bias after injection of dopamine agonists. MCAOϩMHP36 and control groups exhibited no bias in either spontaneous or drug-induced rotation. In contrast to motor recovery, MCAOϩMHP36 grafted rats showed no improvement relative to MCAOϩsham grafted rats in spatial learning and memory in the water maze. MCAO produced large striatal and cortical cavitations in both occluded groups. Lesion volume was significantly reduced (PϽ0.05) in the MCAOϩMHP36 grafted group. The majority of MHP36 cells were identified within the intact grafted hemisphere. However, MHP36 cells were also seen in the cortex, striatum, and corpus callosum of the lesioned hemisphere. Conclusions-MHP36 cells may improve functional outcome after MCAO by assisting spontaneous reorganization in both the damaged and intact hemispheres.

Distribution and in situ proliferation patterns of intravenously injected immortalized human neural stem-like cells in rats with focal cerebral ischemia

“…Previous transplantation (neural progenitors) approaches in ischemic models have been made by injecting progenitors directly into the brain parenchyma, which resulted in tissue damage along the needle passages and limited migration of the precursor cells (Hodges et al, 1996;Modo et al, 2002;Veizovic et al, 2001). As far as we know, this study is the first to report the intravenous administration of human NSCs into focal ischemia model (Savitz et al, 2002).…”

Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex

“…Fetal brain tissue transplants have been shown to produce some recovery in animal models of stroke (2)(3)(4), but ethical considerations and a short supply of human fetal tissue limited this approach. More recently, a host of cell types have been tested in stroke models, including human bone marrow cells (5-7), human umbilical cord blood cells (5,8), rat trophic factor-secreting kidney cells (2,5), and immortalized cell lines such as the human neuron-like NT2N (hNT) cells (9,10) and MHP36, an embryonic murine immortalized neuroepithelial cell line (11,12). In most cases some index of behavioral function has been improved.…”

Intracerebellar Transplantation of Neural Stem Cells into Mice with Neurodegeneration Improves Neuronal Networks with Functional Synaptic Transmission

“…As an example, v-mycimmortalized cerebellar mouse C17.2-CD cells have been shown to efficiently ameliorate clinicopathological feature of neurodegenerative disease model mice [13,27]. MHP36, conditionally immortalized neural stem cells, is also has the capacity to repair and restore cognitive functions in stroke which is one of the diseases characterized neuronal loss and behavioral disorder [18,29]. MHP36 is derived from a transgenic mouse strain carrying the temperature-sensitive (ts) allele of the SV40 large T-oncogene [9].…”