Autologous bone marrow mononuclear cell therapy of ischemic stroke in sheep

Autor: Boltze, J., Dreyer, A., Zeisig, V., Lobsien, D., Gille, U., Wagner, D.C., Kirsten, H., Barthel, H.
Přispěvatelé: Publica
Jazyk: angličtina
Rok vydání: 2015
Popis: Autologous bone marrow mononuclear cell (BMMNC) therapy was proven to be effective in rodent stroke models, and the first phase I/II clinical investigations are under way to assess their therapeutic potential in patients. However, our knowledge on therapeutic mechanisms, proof-of-concept efficacy in gyrencephalic brains, as well as long-term impact on neurofunctional parameters and lesion size development is still fragmentary. Here 32 adult Merino rams were subjected to permanent middle cerebral artery occlusion after an initial health check and prestudy surveillance. Following baseline neurofunctional assessment, animals were subjected to control or autologous BMMNC IV administration (>4.0 × 106 BMMNCs per kg body weight) 24 h after stroke (n = 16 each). Animals were monitored for 42 days by behavioral phenotyping, magnetic resonance imaging (MRI), [15O]- H2O-, and [18F]-fluorodeoxyglucose positron emission tomography (PET) before postmortem histological assessment. All experiments were conducted randomized and blinded, and strict exclusion/inclusion criteria were applied. The therapeutic approach was safe, but eight animals (3× control; 5× BMMNC treated) had to be removed from the trial due to violation of preset inclusion criteria including insufficient BMMNC numbers per kg bodyweight. BMMNC therapy was associated with amelioration of functional deficits from day 7 (p
Databáze: OpenAIRE