Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats

Author(s): Borlongan CV, Tajima Y, Trojanowski JQ, Lee VMY, Sanberg PR

Abstract

This study was designed to explore the efficacy of a human clone cell line as an alternative neural graft source and to validate the practice of cryopreservation and xenografting as logistical approaches toward conducting neural transplantation. We investigated the biological effects of transplanting cultured human neurons (NT2N cells) derived from a well-characterized embryonal carcinoma cell line into the brains of rats subjected to transient, focal cerebral ischemia induced by embolic occlusion of the middle cerebral artery. At 1 month and extending throughout the 6-month posttransplantation test period, ischemic animals that were transplanted with NT2N cells and treated with an immunosuppressive drug displayed a significant improvement in a passive avoidance task as well as a normalization of asymmetrical motor behavior compared to ischemic animals that received rat fetal cerebellar cell grafts or vehicle alone. Remarkably, cryopreserved NT2N cell grafts compared with fresh NT2N cell grafts, remained viable in the immunosuppressed rat brain and effective in producing behavioral recovery in immunosuppressed ischemic animals. The long-term viability of cryopreserved NT2N cell xenografts in vivo and their sustained effectiveness in promoting behavioral recovery suggest potential utilization of xenografting and cryopreservation as useful protocols for establishing clone cell lines as graft source in neural transplantation therapies for central nervous system disorders.

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.