Abstract
BackgroundMesenchymal stromal cells attract much interest in tissue regeneration because of their capacity to differentiate into mesodermal origin cells, their paracrine properties and their possible use in autologous transplantations. The aim of this study was to investigate the safety and reparative potential of implanted human mesenchymal stromal cells (hMSCs), prepared under Good Manufacturing Practice (GMP) conditions utilizing human mixed platelet lysate as a culture supplement, in a collagenase Achilles tendon injury model in rats.MethodsEighty-one rats with collagenase-induced injury were divided into two groups. The first group received human mesenchymal stromal cells injected into the site of injury 3 days after lesion induction, while the second group received saline. Biomechanical testing, morphometry and semiquantitative immunohistochemistry of collagens I, II and III, versican and aggrecan, neovascularization, and hMSC survival were performed 2, 4, and 6 weeks after injury.ResultsHuman mesenchymal stromal cell-treated rats had a significantly better extracellular matrix structure and a larger amount of collagen I and collagen III. Neovascularization was also increased in hMSC-treated rats 2 and 4 weeks after tendon injury. MTCO2 (Cytochrome c oxidase subunit II) positivity confirmed the presence of hMSCs 2, 4 and 6 weeks after transplantation. Collagen II deposits and alizarin red staining for bone were found in 6 hMSC- and 2 saline-treated tendons 6 weeks after injury. The intensity of anti-versican and anti-aggrecan staining did not differ between the groups.ConclusionshMSCs can support tendon healing through better vascularization as well as through larger deposits and better organization of the extracellular matrix. The treatment procedure was found to be safe; however, cartilage and bone formation at the implantation site should be taken into account when planning subsequent in vivo and clinical trials on tendinopathy as an expected adverse event.
Highlights
Mesenchymal stromal cells attract much interest in tissue regeneration because of their capacity to differentiate into mesodermal origin cells, their paracrine properties and their possible use in autologous transplantations
The tendon healing process includes the formation of a hematoma, the local infiltration of inflammatory cells, the release of cytokines and growth factors followed by the formation of new extracellular matrix, new blood vessels and maturation and organization of the tendon tissue
It was repeatedly shown that the delivery of mesenchymal stromal cells can create an optimal environment to support tendon tissue regeneration via the formation of extracellular matrix, enhanced vascularization, the production of supporting factors, modulation of the immunoresponse and the replacement of damaged cells [4,6]
Summary
Mesenchymal stromal cells attract much interest in tissue regeneration because of their capacity to differentiate into mesodermal origin cells, their paracrine properties and their possible use in autologous transplantations. Relevant cellbased therapies often utilize adult stem cells, e.g. multipotent mesenchymal stromal cells. Mesenchymal stromal cells of various origins have been implanted directly into a tendon injury or attached to biodegradable scaffolds used to repair the tendon; they have shown an apparent beneficial effect on the healing process [4] and migrated to the injured tendon [5]. It was repeatedly shown that the delivery of mesenchymal stromal cells can create an optimal environment to support tendon tissue regeneration via the formation of extracellular matrix, enhanced vascularization, the production of supporting factors, modulation of the immunoresponse and the replacement of damaged cells [4,6]
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