Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. Despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring t...Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. Despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring the delicate transitional tissue between bone and tendon. It is essential to understand the molecular mechanisms that determine this failure. The study of the molecular environment during embryogenesis and during normal healing after injury is key in devising strategies to get a successful repair. Mesenchymal stem cells(MSC) can differentiate into different mesodermal tissues and have a strong paracrine, anti-inflammatory, immunoregulatory and angiogenic potential. Stem cell therapy is thus a potentially effective therapy to enhance rotator cuff healing. Promising results have been reported with the use of autologous MSC of different origins in animal studies: they have shown to have better healing properties, increasing the amount of fibrocartilage formation and improving the orientation of fibrocartilage fibers with less immunologic response and reduced lymphocyte infiltration. All these changes lead to an increase in biomechanical strength. However, animal research is still inconclusive and more experimental studies are needed before human application. Future directions include expanded stem cell therapy in combination with growth factors or different scaffolds as well as new stem cell types and gene therapy.展开更多
The aim of this study was to evaluate injectable,in situ cross-linkable elastin-like recombinamers(ELRs)for osteochondral repair.Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenc...The aim of this study was to evaluate injectable,in situ cross-linkable elastin-like recombinamers(ELRs)for osteochondral repair.Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells(rMSCs)were tested for the regeneration of critical subchondral defects in 10 New Zealand rabbits.Thus,cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4months for histological and gross evaluation of features of biomaterial performance,including integration,cellular infiltration,surrounding matrix quality and the new matrix in the defects.Although both approaches helped cartilage regeneration,the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration,whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline cartilage.In conclusion,the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.展开更多
文摘Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. Despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring the delicate transitional tissue between bone and tendon. It is essential to understand the molecular mechanisms that determine this failure. The study of the molecular environment during embryogenesis and during normal healing after injury is key in devising strategies to get a successful repair. Mesenchymal stem cells(MSC) can differentiate into different mesodermal tissues and have a strong paracrine, anti-inflammatory, immunoregulatory and angiogenic potential. Stem cell therapy is thus a potentially effective therapy to enhance rotator cuff healing. Promising results have been reported with the use of autologous MSC of different origins in animal studies: they have shown to have better healing properties, increasing the amount of fibrocartilage formation and improving the orientation of fibrocartilage fibers with less immunologic response and reduced lymphocyte infiltration. All these changes lead to an increase in biomechanical strength. However, animal research is still inconclusive and more experimental studies are needed before human application. Future directions include expanded stem cell therapy in combination with growth factors or different scaffolds as well as new stem cell types and gene therapy.
基金the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No.642687the European Commission(NMP-2014-646075)+2 种基金the Spanish Government(PCIN-2015-010,MAT2015-68901-R,MAT2016-78903-R,MAT2016-79435-R)Junta de Castilla y Leon(VA015U16)Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y Leon.
文摘The aim of this study was to evaluate injectable,in situ cross-linkable elastin-like recombinamers(ELRs)for osteochondral repair.Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells(rMSCs)were tested for the regeneration of critical subchondral defects in 10 New Zealand rabbits.Thus,cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4months for histological and gross evaluation of features of biomaterial performance,including integration,cellular infiltration,surrounding matrix quality and the new matrix in the defects.Although both approaches helped cartilage regeneration,the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration,whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline cartilage.In conclusion,the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.