Kokaia Group

	Zaal Kokaia, PhD Professor Head of the Laboratory Head of Neuroscience Program
Address:	Lab. of Neural Stem Cell Biology Section of Restorative Neurology Lund Strategic Research Center for Stem Cell Biology and Cell Therapy University Hospital BMC B10 SE-221 84 Lund SWEDEN Tel: +46 (46) 222 02 76 Fax: +46 (46) 222 05 60 E-mail: zaal.kokaia@med.lu.s

Link to Section of Restorative Neurology

Main Research Topics

Isolation and charaterization of human and murine neural stem cells and development of transplantation strategies for functional restoration after stroke
Neural stem cells (NSCs) are derived from the nervous system, have capacity for self-renewal and can generate neural tissue. The possibility to isolate and propagate NSC and their potential applications in cell therapy have attracted a lot of research interest in recent years. Conceptually, the idea behind this strategy is rather straightforward: NSCs can be isolated, expanded and/or immortalized in culture, genetically modified, and subsequently transplanted into the diseased human recipient. These cells may replace damaged or died endogenous cells (neurons and /or glia) in the diseased nervous system, and/or provide cellular support (metabolic and/or structural). Among the disorders of central nervous system, neurodegenerative diseases, including stroke, are most suitable for cell therapy strategies. The primary objective of our research is to isolate, characterize and investigate the ability of NSCs to reconstitute stroke-damaged forebrain and support restoration of impaired sensory and motor function. Our specific aims are: i) to isolate human and murine NSCs from different structures of fetal forebrain and develop immortalized NSC lines. ii) to characterize proliferative and differentiation properties of human and murine NSC lines in vitro and investigate factors responsible for their fate determination. iii) to explore the potency of grafted NSC lines to reconstruct stroke-damaged neuronal circuits and promote functional recovery. The planned experiments will help to learn more about basic characteristics of NSCs which is necessary to fully realize the potential of these cells. These experiments will also support further identification of the factors that direct the differentiation of NSCs in certain type of neurons. They may help to identify the ways for activation of endogeneous and grafted NSCs and support repair mechanisms in the damaged parts of nervous system. The extensive propagation and transplantation potential of human NSCs, in close future, may be directed towards clinical use, and may open novel and diverse strategies for therapeutic use in stroke and other neurodegenerative disorders.

Laboratory Members

      
Emanuela Monni, PhD student         
Therese Kallur, PhD student         
Henrik Ahlenius, PhD student       
Carlo Cusulin,  PhD student           

Camilla Andersson, Lab. Assistant +46 (46) 222 01 71

Selected Recent and Key Publications

1. Kokaia Z., Bengzon J., Metsis M., Kokaia M., Persson H. and Lindvall O. Coexpression of neurotrophins and their receptors in neurons of central nervous system. Proc. Natl. Acad. Sci. USA, 1993, 90, 6711-6715.
2. Nanobashvili A., Airaksinen M. S., Kokaia M., Rossi J., Asztély F., Olofsdotter K., Mohapel P., Saarma M., Lindvall O. and Kokaia Z. Development and persistence of kindling epilepsy are impaired in mice lacking glial cell line-derived neurotrophic factor family receptor α2. Proc. Natl. Acad. Sci. USA, 2000, 97, 12312-12317.
3. Arvidson A., Colin, T., Kirik D., Kokaia Z*. and Lindvall O*. Neuronal replacement from endogenous precursors in the adult brain after stroke Nature Medicine, 2002, 8, 963-970.
4. Parmar M., Sjöberg A., Björklund A. and Kokaia Z. Phenotypic and molecular identity of cells in the adult subventricular zone; in vivo and after expansion in vitro. Molecular and Cellular Neuroscience, 2003, 24, 741-752.
5. Ekdahl C.T., Claasen J.-H., Bonde S., Kokaia Z. and Lindvall O. Inflammation is detrimental for neurogenesis in adult brain.
Proc. Natl. Acad. Sci., 2003, 100, 13632-13637.
6. Lindvall O., Kokaia Z.* and Martinez-Serrano, A.* Stem cell therapy for human neurodegenerative disorders–how to make it work. Nature Medicine, 2004, 10, S42-S50. *- equal contribution.
7. Darsalia V., Hendlund U., Lindvall O. and Kokaia Z. Stroke-induced neurogenesis in aged brain. Stroke, 2005, 36, 1790-1795.
8. Lindvall O. and Kokaia Z. Stem cells for treatment of neurological disorders. Nature, 2006, 441, 1094-1096.
9. Kallur T., Darsalia V., Lindvall O. and Kokaia Z. Human fetal cortical and striatal neural stem cells generate region-specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats. Journal of Neuroscience Research, 2006, 84, 1630-1644.
10. Cacci E., Villa A., Parmar M., Mandahl N., Lindvall O., Martinez-Serrano A. and Kokaia Z. Generation of human cortical neurons from a new immortal fetal neural stem cell line. Experimental Cell Research, 2006, 313, 588-601.
11. Darsalia V., Kallur T. and Kokaia Z. Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke-damaged rat striatum.
European Journal of Neuroscience,  2007, 26, 605-614.