Construction of a vector for controlled expression of chondroitinase AC for mesenchymal stem cells / Construção de um vetor para expressão controlada de condroitinase AC por células tronco mesenquimais/

AUTOR(ES)

Caroline Mônaco Moreira

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

22/02/2011

RESUMO

Adult mammal axons fail to regenerate when damaged, generating a fundamental problem, inhibiting the recovery of injured central nervous system (CNS). The lack of full regenerative capacity of the injured CNS is due to a glial scar formation on the injury site. The glial scar is formed by astrocytes, oligodendrocyte precursor cells, and microglia, cells that produce molecules that inhibit axonal regeneration. Chondroitin sulphate proteoglycans are the major responsible for this inhibitory characteristic. Chondroitin sulphate chain degradation by enzymes named chondroitinases reduces local inhibition and increases axonal regeneration. Another possibility to treat CNS injury is cell therapy using mesenchymal stem cells (MSC). MSC can be used to repair injured tissues providing new cells, to replace the damaged ones, or as a source of trophic factors, stimulating the regeneration by secreting bioactive factors. In the present work, we used a combination of two approaches for the treatment of injured CNS: gene and cellular therapies. We have produced a retroviral vector containing the gene for chondroitinase AC (cAC), for the controlled expression of the enzyme, produced the correspondent viruses and tested their transduction capacity in CHO and 9L cells. The expression of cAC was observed in CHO cells. In parallel, we have cultivated MSC that were also transduced with the viruses; however, we have not observed the cAC expression in these cells, suggesting a possible silencing mechanism. Although more studies are needed to the cAC expression by MSC, the combined use of MSC and cAC can be a useful tool for the treatment of injured SNC.

ASSUNTO(S)

vetores retrovirais microbiologia lesão no snc cicatriz glial proteoglicanos de condroitim sulfato condroitinase ac células tronco mesenquimais

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