| Autor: |
Islamov RR; Kazan State Medical University, Kazan, Russia. islamru@yahoo.com.; Department of Biology, Kazan State Medical University, ul. Butlerova 49, R-420012, Kazan, Russia. islamru@yahoo.com., Rizvanov AA; Kazan Federal University, Kazan, Russia., Fedotova VY; Kazan Federal University, Kazan, Russia., Izmailov AA; Kazan State Medical University, Kazan, Russia., Safiullov ZZ; Kazan Federal University, Kazan, Russia., Garanina EE; Kazan State Medical University, Kazan, Russia., Salafutdinov II; Kazan Federal University, Kazan, Russia., Sokolov ME; Kazan State Medical University, Kazan, Russia., Mukhamedyarov MA; Kazan State Medical University, Kazan, Russia., Palotás A; Kazan Federal University, Kazan, Russia. palotas@asklepios-med.eu.; Asklepios-Med (private medical practice and research center), Kossuth Lajos sgt. 23, Szeged, H-6722, Hungary. palotas@asklepios-med.eu. |
| Abstrakt: |
Current treatment options of chronic, progressive degenerative neuropsychiatric conditions offer only marginal efficacy, and there is no therapy which arrests or even reverses these diseases. Interest in genetic engineering and cell-based approaches have constantly been increasing, although most of them so far proved to be fruitless or at best provided very slight clinical benefit. In the light of the highly complex patho-mechanisms of these maladies, the failure of drugs aimed at targeting single molecules is not surprising. In order to improve their effectiveness, the role of a unique triple-combination gene therapy was investigated in this study. Intravenous injection of human umbilical cord blood mononuclear cell (hUCBMC) cotransduced with adenoviral vectors expressing vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) resulted in prominent increase of life span and performance in behavioral tests in amyotrophic lateral sclerosis (ALS). Expression of the recombinant genes in hUCBMCs was confirmed as soon as 5 days after transduction by RT-PCR, and cells were detectable for as long as 1 month after grafting in lumbar spinal cord by immunofluorescent staining. Xenotransplantation of cells into mice blood without any immunosuppression demonstrated a high level of hUCBMCs homing and survivability in the central nervous system (CNS), most conspicuously in the spinal cord, but not in the spleen or liver. This study confirms an increased addressed homing and notable survivability of triple-transfected cells in lumbar spinal cord, yielding a remarkably enhanced therapeutic potential of hUCBMCs overexpressing neurotrophic factors. |
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