Stem Cell Therapy for Tendon Regeneration: Current Status and Future Directions.

In adults the healing tendon generates fibrovascular scar tissue and recovers never histologically, mechanically, and functionally which leads to chronic and to degenerative diseases. In this review, the processes and mechanisms of tendon development and fetal regeneration in comparison to adult defect repair and degeneration are discussed in relation to regenerative therapeutic options. We focused on the application of stem cells, growth factors, transcription factors, and gene therapy in tendon injury therapies in order to intervene the scarring process and to induce functional regeneration of the lesioned tissue. Outlines for future therapeutic approaches for tendon injuries will be provided.

Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions--a pilot study.

BACKGROUND: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. METHODS: Four adult warmblood horses received a unilateral injection of 10 × 10(6) autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. RESULTS: AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. CONCLUSIONS: Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 × 10(6) AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional administration. Injection techniques have to be chosen deliberately to avoid reflux of the cell substrate injected. In vivo low-field MRI may be used as a non-invasive tool to monitor homing and engraftment of AT-MSCs in horses with tendinopathy of the SDFT.

Evaluation of the efficacy of meloxicam for post-operative management of pain and inflammation in horses after orthopaedic surgery in a placebo controlled clinical field trial.

BACKGROUND: The benefit of pre and post-operative administration of non-steroidal anti-inflammatory drugs for the relief of post-operative pain and control of inflammation in horses following orthopaedic surgery has not been previously investigated in controlled clinical field trials, and the utility of such treatment is a matter of ongoing dispute. Recently the utility of post-operative pain management was emphasized. It was therefore our aim to determine the efficacy of meloxicam in horses following partial resection of fractured splint bones. This condition was selected since the limited extent of the insult and the defined surgical intervention allowed the conduct of a randomized, double blinded, placebo-controlled, parallel group, multi-centre clinical field study in a homogenous patient population. RESULTS: Sixty-six client owned horses requiring unilateral partial splint bone resection were recruited in 15 centres in Germany and were allocated in a 1:1 ratio to receive meloxicam, 0.6 mg/kg for 5 days. Lameness at trot grades prior to surgery were similar in the meloxicam and placebo treatment groups but were significantly lower in the meloxicam group on day 6 post surgery. Clinical scores for soft tissue swelling and assessment of analgesic and anti-inflammatory efficacy by the investigators at the end of the study were significantly better for the meloxicam compared to the placebo group. No treatment-related adverse reactions were observed. CONCLUSION: The administration of meloxicam i.v. once prior to surgery followed by once daily oral administration for four consecutive days is efficacious for the control of post-operative pain and inflammation in horses undergoing orthopaedic surgery.

Evaluation of the osteogenic and chondrogenic differentiation capacities of equine adipose tissue-derived mesenchymal stem cells.

OBJECTIVE: To evaluate the proliferative behavior, telomere length, immunophenotype, and differentiation capacity of equine adipose tissue-derived mesenchymal stem cells (AT-MSCs). ANIMALS: 6 adult racing horses treated for articular Injury but otherwise healthy. PROCEDURES: AT-MSCs were Isolated from horses and expanded In Dulbecco modified Eagle medium enriched with fetal bovine serum and antimicrobials. Expression of cell surface antigens and telomere length were Investigated via flow cytometry Differentiation of MSCs Into chondrocytes, osteoblasts, and adipocytes was Induced In vitro by specific stimuli and was evaluated by analyzing marker genes with quantitative reverse transcriptase PCR assays and immunocytochemical and cytologie evaluations. RESULTS: Equine MSCs could be cultured up to the fifth passage before signs of senescence, apoptosis, and detachment Indicated cellular exhaustion. However, the AT-MSCs from 2 of 6 horses survived to later passages with Increased doubling rates and telomere lengths. The cells had a typical phenotype, with expression of CD14, CD73, CD90, CD105, CD140b, and CD164 antigens and a lack of CD34 and CD45 antigens. The cells also had a strong potential to differentiate Into osteoblasts, as characterized by Intense von Kossa and alizarin red staining as well as high Induction of osteopontin. Chondrogenic differentiation was detected via Alelan blue staining and expression of aggrecan and type II collagen Adipogenesis was Induced in AT-MSCs by supplementation of differentiation media with rabbit serum. CONCLUSIONS AND CLINICAL RELEVANCE: Equine AT-MSCs representa suitable cellular source for regenerative treatment of bone or cartilage defects, particularly when expanded In vitro for only a few passages.