2007. Vol. 49, N 11. p. 923-932
MESENCHYMAL STEM CELLS TRANSPLANTATION INFLUENCES UPON DYNAMICS OF MORPHOLOGICAL CHANGES IN RAT BRAIN AFTER STROKE

N. N. Zinkova,1, * E. G. Gilerovich,2 I. B. Sokolova,2 E. V. Shvedova,1 A. A. Bilibina,1 P. V. Kruglyakov,1 D. G. Polyntsev 1

1 «Trans-Technologies», Ltd., and 2 State Research Institute of Experimental Medicine RAMS, St. Petersburg;
* e-mail: natalia_z@alkorbio.ru

Study of dynamic morphological changes if the brain after ischemic stroke is an important phase of pre-clinical trial of mesenchymal stem cell (MSC) therapy for this widespread disease. Experoments were carried out in inbred Wistar-Kyoto rats. MSCs were isolated, expanded in culture and labeled with vital fluorescent dye PKH26. Animals were subjected to middle cerebral artery occlusion (MCAO) followed by injection of 5·106 rat MSCs into the tail vein on the day of MCAO. Control group of animals received PBS injection (negative control). Animals were sacrificed in 1, 2, 3 and 5 days and in 1, 2, 4 and 6 weeks after operation. MSCs were revealed in the brain on the third day transplantation. They distributed around brain vessels in both the ipsilateral and contralateral hemispheres. This pattern of distribution remained unchanged during 6 weeks of observation. It was demonstrated that inflammation process and scar formation in the experimental group progressed 25—30 % faster than in the control group. MSC transplantation stimulated endogenous stem cell proliferation on the subependimal zone of lateral ventricles (subventrecular zone). What is more, MSC injection showed neuroprotective effect: almost all penumbra neurons in animals treated with cell therapy retained their normal structure, whereas in animals of control group penumbra neurons died or had signs of serious damage.

Key words:  mesenchymal stem cells, ischemic stroke, glial scar, proliferation, neurons, penumbra


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