Cell therapy for stroke: remaining issues to address before embarking on clinical trials

Author(s): Borlongan CV

Abstract

Background and purpose: Stroke remains a significant clinical unmet condition, with only 3% of ischemic patient population benefiting from the thrombolytic drug tissue plasminogen activator largely because of the drug's narrow 3-hour therapeutic window. Extending the stroke therapeutic window will greatly impact on treatment, care, and management of patients. Summary of Review- Cell therapy is appealing in this regard as it widens the stroke treatment opportunity by targeting the neurorestorative phase (ie, several hours to days and even weeks or months after stroke). Although compelling preclinical evidence reveals that transplantation of stem/progenitor cells is safe and effective in animal models of stroke, the laboratory data need to be evaluated on their translational relevance for clinical application. In addressing this issue, I borrow heavily from the conference proceedings of the 2007 STEPS (Stem Cell Therapeutics as an Emerging Paradigm in Stroke).

Conclusions: Translational research guidelines are being adapted by academic institutes, industry, National Institutes of Health (NIH), and Food and Drug Administration (FDA), and adhering to these preclinical criteria will provide the basis for advancing cell therapy in stroke from the laboratory to the clinic.

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.