Development of 3D culture models for human ucmMSC-derived hepatocytes for predictive toxicology and cell therapy

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Effects of umbilical cord tissue mesenchymal stem cells (UCX®) on rat sciatic nerve regeneration after neurotmesis injuries

Publication . Gärtner, A.; Pereira, T.; Armada-da-Silva, P. A. S.; Amado, S.; Veloso, A. P.; Amorim, I.; Ribeiro, J.; Santos, J. D.; Bárcia, R. N.; Cruz, P.; Cruz, H.; Luís, A. L.; Santos, J. M.; Geuna, S.; Maurício, A. C.

Abstract Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs) may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX®), was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal®, was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT), withdrawal reflex latency (WRL), ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX® alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX® induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC). At opposite toe off (OT) and heel rise (HR), differences were found between untreated animals and the groups treated with either UCX® alone or UCX® administered with Floseal®. Overall, the UCX® application presented positive effects in functional and morphologic recovery, in both the acute and chronic phases of the regeneration process. Kinematics analysis has revealed positive synergistic effects brought by Floseal® as vehicle for MSCs.

2014-04-30Artigo de investigação

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Palavras-chave

ucmMSC,hepatocite-like cells,three-dimensional cultures,drug metabolism, Medical and health sciences

Entidade financiadora

Fundação para a Ciência e a Tecnologia, I.P.

Programa de financiamento

Concurso para Projectos de I&D em todos os Domínios Científicos - 2009

Número da atribuição

PTDC/SAU-TOX/110457/2009