Bystander effect of Human Umbilical Cord Blood Mononuclear Cells administered systemically in long-term repair processes after brain injury

• Autorzy: Kozlowska H. , Pawlak E. , Habich A. , Janowski M. , Jablonska A. , Wanacka E. , Lukomska D. , Domanska-Janik K.
• Języki publikacji: EN

Abstrakty

EN

Stem cell transplantation offers an exciting new therapeutic avenue for stroke not only to prevent damage, which has been the focus of conventional therapeutic strategies, but also to actually repair the injured brain. Indeed, exogenous stem cell grafting in animal models of CNS damage improves function by replacing the lost neurons. However, therapeutic mechanism different from the expected contribution of cell replacement have been also postulated. Many studies applying systemic delivery of cells in ischemic stroke disorders have shown significant functional recovery with very few or frequently no cells entering brain. It seems that transplanted cells could propel local micro-environmental signals to sustain active endeavors for damaged neurons substitution. The question arises if systemic infusion of cells enhances endogenous neurogenesis previously activated by focal ischemic brain injury. Materials and methods: Experimental model of focal ischemic brain injury was performed by local application of Na/K ATP-ase pump inhibitor - ouabain (OUA) (1 µl/50nmol) into the striatum of CsA-immunosuppressed adult Wistar rats. Three days later 107 human umbilical cord blood CD34- mononuclear cells (HUCB-MNC) were infused into internal carotic artery. At 30 day thereafter rat brains were removed and the neurogenic regions and tissue around the damaged areas were analyzed immunohistochemically. Results: Analysis of brain tissue in OUA injured rats transplanted with HUCB-MNC revealed augmentation of proliferative cells (Ki-67+) in subventricular zone (SVZ) of ipsilateral hemisphere and at the border of the lesion area as well as higher number of DCX+ cells in SVZ. Moreover, the extensive neuroblast migration and their accumulation in the perinfarct striatum were observed in comparison to non-transplanted rats after OUA injury onset. HUCB-MNC injection into rats with brain infarct showed a significant increase of cells with immature (Nestin+) or more mature (NF-200+) neuronal phenotypes observed in the tissue alongside OUA lesion. The intensive staining of GFAP at the border of injured area in HUCB-MNC transplanted and nontransplanted rats reflected gliosis however, the increased expression of GFAP in brain tissue of the former ones may point to the possible expansion of endogenous progenitors. In conclusions, HUCB-MNC transplanted systemically into OUA focal ischemic brain injured rats activate the endogenous stem cell compartment where the newly arisen cells adopt a neuronal or astrocytic fate. This effect may prove applicable for future clinical therapy. Supported by MSHE grants: 0142/B/P01/2008/35 and 0394/B/ P01/2010/38

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

Twórcy

autor

Kozlowska H.

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

autor

Pawlak E.

• 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

Janowski M.

• 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

Wanacka E.

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

autor

Lukomska D.

• 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