Injured Achilles Tendons Treated with Adipose-Derived Stem Cells Transplantation and GDF-5
| Autor: | Giane Daniela Carneiro, João Bosco Pesquero, Cristina P. Vicente, Gustavo Ferreira Simões, Alexandre Leite Rodrigues de Oliveira, Marcelo Augusto Marreto Esquisatto, Luis Felipe Rodrigues Teodoro, Lúcia Elvira Alvares, Benedicto de Campos Vidal, Priscyla Waleska Targino de Azevedo Simões, Fernanda Cristina da Veiga, Andrea Aparecida de Aro, Caio Perez Gomes, Edson Rosa Pimentel, Danilo Lopes Ferrucci |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
collagen Pathology medicine.medical_specialty extracellular matrix Adipose tissue gait Regenerative medicine Article biomechanics Extracellular matrix 03 medical and health sciences Paracrine signalling medicine CD90 lcsh:QH301-705.5 030102 biochemistry & molecular biology business.industry Mesenchymal stem cell Osteoblast General Medicine Tendon 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) repair gene expression business |
| Zdroj: | Cells Volume 7 Issue 9 Cells, Vol 7, Iss 9, p 127 (2018) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells7090127 |
| Popis: | Tendon injuries represent a clinical challenge in regenerative medicine because their natural repair process is complex and inefficient. The high incidence of tendon injuries is frequently associated with sports practice, aging, tendinopathies, hypertension, diabetes mellitus, and the use of corticosteroids. The growing interest of scientists in using adipose-derived mesenchymal stem cells (ADMSC) in repair processes seems to be mostly due to their paracrine and immunomodulatory effects in stimulating specific cellular events. ADMSC activity can be influenced by GDF-5, which has been successfully used to drive tenogenic differentiation of ADMSC in vitro. Thus, we hypothesized that the application of ADMSC in isolation or in association with GDF-5 could improve Achilles tendon repair through the regulation of important remodeling genes expression. Lewis rats had tendons distributed in four groups: Transected (T), transected and treated with ADMSC (ASC) or GDF-5 (GDF5), or with both (ASC+GDF5). In the characterization of cells before application, ADMSC expressed the positive surface markers, CD90 (90%) and CD105 (95%), and the negative marker, CD45 (7%). ADMSC were also differentiated in chondrocytes, osteoblast, and adipocytes. On the 14th day after the tendon injury, GFP-ADMSC were observed in the transected region of tendons in the ASC and ASC+GDF5 groups, and exhibited and/or stimulated a similar genes expression profile when compared to the in vitro assay. ADMSC up-regulated Lox, Dcn, and Tgfb1 genes expression in comparison to T and ASC+GDF5 groups, which contributed to a lower proteoglycans arrangement, and to a higher collagen fiber organization and tendon biomechanics in the ASC group. The application of ADMSC in association with GDF-5 down-regulated Dcn, Gdf5, Lox, Tgfb1, Mmp2, and Timp2 genes expression, which contributed to a lower hydroxyproline concentration, lower collagen fiber organization, and to an improvement of the rats&rsquo gait 24 h after the injury. In conclusion, although the literature describes the benefic effect of GDF-5 for the tendon healing process, our results show that its application, isolated or associated with ADMSC, cannot improve the repair process of partial transected tendons, indicating the higher effectiveness of the application of ADMSC in injured Achilles tendons. Our results show that the application of ADMSC in injured Achilles tendons was more effective in relation to its association with GDF-5. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|