Injured Achilles Tendons Treated with Adipose-Derived Stem Cells Transplantation and GDF-5

Author(s):Show less -

de Aro, Andrea Aparecida ^{[1, 2]} ; Carneiro, Giane Daniela ^[1] ; Teodoro, Luis Felipe R. ^[1] ; da Veiga, Fernanda Cristina ^[3] ; Ferrucci, Danilo Lopes ^[1] ; Simoes, Gustavo Ferreira ^[1] ; Simoes, Priscyla Waleska ^[4] ; Alvares, Lucia Elvira ^[3] ; de Oliveira, Alexandre Leite R. ^[1] ; Vicente, Cristina Pontes ^[1] ; Gomes, Caio Perez ^[5] ; Pesquero, Joao Bosco ^[5] ; Esquisatto, Marcelo Augusto M. ^[2] ; Vidal, Benedicto de Campos ^[1] ; Pimentel, Edson Rosa ^[1]

Affiliation

^[1] State Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Charles Darwin S-N, CP 6109, BR-13083970 Campinas, SP - Brazil

^[2] Herminio Ometto Univ Ctr UNIARARAS, Biomed Sci Grad Program, BR-13607339 Araras, SP - Brazil

^[3] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Charles Darwin S-N, CP 6109, BR-13083970 Campinas, SP - Brazil

^[4] Univ Fed ABC UFABC, Engn Modeling & Appl Social Sci Ctr CECS, Biomed Engn Grad Program PPGEBM, Alameda Univ S-N, BR-09606045 Sao Bernardo Do Campo, SP - Brazil

^[5] Fed Univ Sao Paulo Unifesp, Dept Biophys, Pedro de Toledo 699, BR-04039032 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CELLS; v. 7, n. 9 SEP 2018.
• Web of Science Citations: 6

Abstract

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' 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. (AU)

• FAPESP's process: 12/14973-8 - Effects of the cell therapy using adipose-derived stem cells associated with the gdf-5 on the repair process of injured calcaneal tendon of rats
• Grantee: Andréa Aparecida de Aro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral