Resolution of stroke deficits following contralateral grafts of conditionally immortal neuroepithelial stem cells

Author(s): Veizovic T, Beech JS, Stroemer RP, Watson WP, Hodges H

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 microL of cell suspension (25 000 cells per microliter). Sham grafted rats received equivalent volumes of vehicle. Three groups, sham-operated controls (n=11), MCAO+sham grafts (n=10), and MCAO+MHP36 grafts (n=11), were compared in 3 behavioral tests.

Results: In the bilateral asymmetry test, MCAO+MHP36 grafted rats exhibited neglect before grafting but subsequently showed no significant dysfunction, whereas MCAO+sham grafted rats showed stable sensorimotor deficits over 18 weeks relative to controls. MCAO+sham grafted rats demonstrated spontaneous motor asymmetry and increased rotational bias after injection of dopamine agonists. MCAO+MHP36 and control groups exhibited no bias in either spontaneous or drug-induced rotation. In contrast to motor recovery, MCAO+MHP36 grafted rats showed no improvement relative to MCAO+sham 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 (P<0.05) in the MCAO+MHP36 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.

Similar Articles

Neurological emergencies: acute stroke

Author(s): Davenport R, Dennis M

Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke

Author(s): Fagan SC, Morgenstern LB, Petitta A, Ward RE, Tilley BC, et al.

REACH: clinical feasibility of a rural telestroke network

Author(s): Hess DC, Wang S, Hamilton W, Lee S, Pardue C, et al.

Remote evaluation of acute ischemic stroke in rural community hospitals in Georgia

Author(s): Wang S, Gross H, Lee SB, Pardue C, Waller J, et al.

Gene therapy, cell transplantation and stroke

Author(s): Borlongan CV, Fournier C, Stahl CE, Yu G, Xu L, et al.

Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke

Author(s): Matsukawa N, Yasuhara T, Hara K, Xu L, Maki M, et al.

The albumin in acute stroke trial (ALIAS); design and methodology

Author(s): Hill MD, Moy CS, Palesch YY, Martin R, Dillon CR, et al.

Grafting neural stem cells improved the impaired spatial recognition in ischemic rats

Author(s): Toda H, Takahashi J, Iwakami N, Kimura T, Hoki S, et al.

Adult rat and human bone marrow stromal cells differentiate into neurons

Author(s): Woodbury D, Schwarz EJ, Prockop DJ, Black IB

Bone marrow as a source of endothelial cells and NeuN-expressing cells After stroke

Author(s): Hess DC, Hill WD, Martin-Studdard A, Carroll J, Brailer J, et al.

Intravenous versus intrastriatal cord blood administration in a rodent model of stroke

Author(s): Willing AE, Lixian J, Milliken M, Poulos S, Zigova T, et al.

Origin of endothelial progenitors in human postnatal bone marrow

Author(s): Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, et al.

Autologous bone marrow stem cell neurotransplantation in stroke patients

Author(s): Suárez-Monteagudo C, Hernández-Ramírez P, Alvarez-González L, García-Maeso I, de la Cuétara-Bernal K, et al.

Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli

Author(s): Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, et al.

Engineering mesenchymal stem cells for immunotherapy

Author(s): Jorgensen C, Djouad F, Apparailly F, Noël D

Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells

Author(s): Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, et al.

Ischaemic brain oedema

Author(s): Ayata C, Ropper AH

Inflammation markers and prediction of post-stroke vascular disease recurrence: the MITICO study

Author(s): Castillo J, Alvarez-Sabín J, Martínez-Vila E, Montaner J, Sobrino T, et al.

Proinflammatory cytokines and early neurological worsening in ischemic stroke

Author(s): Vila N, Castillo J, Dávalos A, Chamorro A

Mechanisms of ischemic brain damage

Author(s): Doyle KP, Simon RP, Stenzel-Poore MP

Evidence for circulating bone marrow-derived endothelial cells

Author(s): Shi Q, Rafii S, Wu MH, Wijelath ES, Yu C, et al.

Reduced number of circulating endothelial progenitors and HOXA9 expression in CD34+ cells of hypertensive patients

Author(s): Pirro M, Schillaci G, Menecali C, Bagaglia F, Paltriccia R, et al.

Bone marrow endothelial progenitors are defective in systemic sclerosis

Author(s): Del Papa N, Quirici N, Soligo D, Scavullo C, Cortiana M, et al.

Defective vasculogenesis in systemic sclerosis

Author(s): Kuwana M, Okazaki Y, Yasuoka H, Kawakami Y, Ikeda Y

Impaired progenitor cell activity in age-related endothelial dysfunction

Author(s): Heiss C, Keymel S, Niesler U, Ziemann J, Kelm M, et al.

Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers

Author(s): Kondo T, Hayashi M, Takeshita K, Numaguchi Y, Kobayashi K, et al.

Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia

Author(s): Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, et al.

Transplantation of low dose CD34+KDR+ cells promotes vascular and muscular regeneration in ischemic limbs

Author(s): Madeddu P, Emanueli C, Pelosi E, Salis MB, Cerio AM, et al.

Endothelial progenitor cell research in stroke: a potential shift in pathophysiological and therapeutical concepts

Author(s): Rouhl RP, van Oostenbrugge RJ, Damoiseaux J, Tervaert JW, Lodder J

Autologous bone marrow mononuclear cell transplantation in patients undergoing coronary artery bypass grafting

Author(s): Mocini D, Staibano M, Mele L, Giannantoni P, Menichella G, et al.

Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure

Author(s): Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, et al.

Unchain my heart: the scientific foundations of cardiac repair

Author(s): Dimmeler S, Zeiher AM, Schneider MD

Circulating CD34-positive cells provide an index of cerebrovascular function

Author(s): Taguchi A, Matsuyama T, Moriwaki H, Hayashi T, Hayashida K, et al.

Endothelial progenitor cells during cerebrovascular disease

Author(s): Ghani U, Shuaib A, Salam A, Nasir A, Shuaib U, et al.