Functional effect of human umbilical cord blood-derived mononuclear cells (HUCB-MNC) transplanted systemically into focal brain injured rats

• Autorzy: Pawlak E. , Janowski M. , Habich A. , Jablonska A. , Drela K. , Lukomska B. , Domanska-Janik K.
• Języki publikacji: EN

Abstrakty

EN

Cerebral ischemia causes severe functional deficits due to the death of neuronal and glial cells in the cortex and sub-cortical regions. Stem cell-based therapy could be used to restore lost cells and thus may enhance functional recovery. The aim of the study was to compare therapeutic effectiveness of intra-arterial infusion of human umbilical cord-blood derived mononuclear cells (HUCB-MNC) at different stages of their neural conversion in vitro. Materials and methods. Freshly isolated HUCB-MNC (D-0) neurally directed progenitors (D-3) obtained during 3 days culture of HUCB-MNC and neural-like stem cells (HUCB-NSC) line derived from human cord blood cells were assessed. Focal brain damage was induced in Wistar rats by stereotactic injection of previously established low dose of ouabain into dorsolateral striatum Three days later 107 HUCB cells were infused into internal carotid artery. Following surgery rats were housed in large enriched environment cages, in groups of 7-8 animals per cage, for 30 days observation period. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam task, rotarod, vibrissae elicited forelimb placing), cognitive impairments (habit learning task and object recognition test), exploratory behavior (open field test) and apomorphine induced rotations. At the end of 30 days observation the lesion volume was measured and the presence of donor cells visualized by the expression of mRNA of human reference gene β-2-microglobulin. Results. Functional effects of different subsets of HUCB-MNC treatment shared substantial diversity in various behavioral tests. In walking beam test the most effective in recovery the impaired sensomotor functions in focal brain injured rats were freshly isolated HUCB-MNC (D-0). Also, in rotarod task and in apomorphine induced rotations the tendency to improve scores was observed 30 days following HUCB-MNC (D-0) treatment. In parameters describing open field exploratory behavior the positive effects of HUCB-MNC (D-0) as well as HUCB-NSC cells treatment were observed. However, in cognitive tasks none of tested cell subsets reduced the functional deficits induced by ouabain injection. Thirty days after HUCB cell transplantation we did not observed any mRNA expression of human reference gene in the rat brain samples. Conclusions. Our observation reveals that freshly isolated D-0 HUCB-MNC are the most effective in functional recovery of injured rats. These cells are also the most potent in reducing the ouabain-induced brain lesion volume. The best functional outcome observed after transplantation of HUCB-MNC (D-0) is probably due to the positive effect of therapeutic molecules secreted by these cells than the persistence of donor per se in the host since we did not detect systemically infused human cells in rat brains. Supported by MSHE grant no. 0394/B/P01/2010/38.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.174-175

Twórcy

autor

Pawlak E.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Janowski M.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Habich A.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Jablonska A.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Drela K.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Lukomska B.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland

autor

Domanska-Janik K.

• Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, Warsaw, Poland