Chemically modified RNA induces osteogenesis of stem cells and human tissue explants as well as accelerates bone healing in rats.
Biomaterials
; 87: 131-146, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26923361
ABSTRACT
Limitations associated to the use of growth factors represent a major hurdle to musculoskeletal regeneration. On the one hand, they are needed to induce neo-tissue formation for the substitution of a necrotic or missing tissue. On the other hand, these factors are used in supraphysiological concentrations, are short lived and expensive and result in many side effects. Here we develop a gene transfer strategy based on the use of chemically modified mRNA (cmRNA) coding for human bone morphogenetic protein 2 (hBMP-2) that is non-immunogenic and highly stable when compared to unmodified mRNA. Transfected stem cells secrete hBMP-2, show elevated alkaline phosphatase levels and upregulated expression of RunX2, ALP, Osterix, Osteocalcin, Osteopontin and Collagen Type I genes. Mineralization was induced as seen by positive Alizarin red staining. hBMP-2 cmRNA transfected human fat tissue also yielded an osteogenic response in vitro as indicated by expression of hBMP-2, RunX2, ALP and Collagen Type I. Delivering hBMP-2 cmRNA to a femur defect in a rat model results in new bone tissue formation as early as 2 weeks after application of very low doses. Overall, our studies demonstrate the feasibility and therapeutic potential of a new cmRNA-based gene therapy strategy that is safe and efficient. When applied clinically, this approach could overcome BMP-2 growth factor associated limitations in bone regeneration.
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Base de dados:
MEDLINE
Assunto principal:
Osteogênese
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Células-Tronco
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Regeneração Óssea
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RNA Mensageiro
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Transfecção
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Proteína Morfogenética Óssea 2
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Fêmur
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article