Cell source and injected cell number | Supplement | Follow-up | Evaluation | Observation | Pros/cons | Reference |
---|---|---|---|---|---|---|
BM-MSCs 5 × 106 in 1 ml | – | 3 years | Comparison with 2 large study with the same follow-up but treated in other ways for 141 horses with natural model injury (overstrain) | No side effects; reduction of the re-injury rate | Long-term efficacy of MSCs/not include the contralateral limb | [16] |
BM-MSC 10 × 106 in 2 ml | BM supernatant | 3 months | Comparison of the effect of supernatant alone or with cell on collagen fibril size and tensile strength (surgical model) | No difference in collagen fibril diameter and strength between control injury and treated injury | The surgical model for tendon injury induces standardized traumatic fiber damage/the surgical model does not represent certain aspects of natural injury | [17] |
ADNC | – | 6 weeks | Short-term efficacy of ADNC fractions for 8 horses with collagenase-induced tendinitis | Improved tendon organization and COMP expression in treated tendons | Cons: long-term studies are needed | [15] |
ASCs 10 × 106 in 0.5 ml | – | 120 days | Effect of cell therapy for 8 horses with collagenase-induced tendonitis | No adverse effects; minimal cellularity; parallel arranged extracellular matrix similar to normal tendon; greater collagen deposits compared with the control group | Cons: long-term studies are needed, and biomechanical and genetic expression analyses are needed | [18] |
ASCs 10 × 106 in 1 ml | PC | 16 weeks | Effect of AD-MSCs combined with PC for therapy of 8 horses with collagenase-induced tendonitis | Greater organization; decreased inflammation; increased blood flow; no difference in the expression of the SCX, TNMD., COL 1 and 3, and TNC between the control and treatment groups | Double centrifugation for the collection of the PC/non-activated PC | [19] |
ASCs 1 × 106 in 5–10 ml | PRP | 9 months | Effect of single injection of cells in 9 athletic horses with spontaneous and acute lameness of SDFT | Decrease in the size of the lesion after 60 days; full alignment of tendon fibers after 120 days; seven horses resumed their normal competitive activity after 7 or 9 months; two horses had relapsed | Pros: rehabilitation program after cell therapy | [20] |
Allogeneic ASCs 2 × 106 in 1 ml | PRP | 24 weeks | Safety and efficacy of a therapy of 19 horses with acute (less than 10 days old) or sub-acute (less than 20 days old) overstrain SDFT injury | No immune response existed; 89.5% of the horses returned to their previous competing level | Rehabilitation program/no control group was included; higher number of animals; histological, biochemical, and biomechanical data is required | [21] |
ASCs 10 × 106 in 2 ml (1.5 ml injected) | – | Up to 9 weeks | Potential low-field MRI to monitor the fate of cells labeled with SPIO nanoparticles (surgical model tendinopathy) | High numbers of cells were present in lesion site | Small number of horses were included; controlled clinical trials are needed; monitoring for a longer time is needed | [22] |
Labeled ASCs 10 × 106 in 1 ml | Serum | 24 weeks | Long-term cell tracking of MSC after local application into tendon lesions and its effect on tendon healing (surgical procedure with collagenase application) | Part of cells appeared to remain viable and integrated within the injured tissue; no difference between MSC-treated tendons and the serum-injected controls at 24 weeks | MRI is an advantageous for long-term tracking/MRI is not suitable for systemic distribution of labeled cells; SPIO-induced hypointense artifacts. Exact percentage of cells surviving is needed | |
Allogeneic UCB-MSCs 2–10 × 106 in ml |  | 6 months | Therapeutic effect of repeated injection UCB-MSCs on tendon and ligament of 52 horses; natural core lesion/anechogenic diffuse lesion | 77% (40 horses) regained their higher level of performance | Cons: lack of a sufficient control group | [25] |
oAECs 7 × 106 in 0.5 ml | – | 18 months, 180 days | Efficacy of healing process in fifteen horses with acute tendon lesions; efficacy of regeneration in acute and chronic lesion | Any adverse reaction to oAEC xenotransplantation and 12 horses resumed competition and their previous activity after 18 months; outcome was similar in both acute and chronic lesions after 180 days | Long-term follow-up/optimal number of injected cells and higher number of chronic cases is required | |
BM-MSC and ESC 1 × 106 in 0.5 ml | – | 3 months | Monitor survival of injected cells into lesion (surgical model) | BM-MSC survival was less than 5% after 10 days; ESC numbers were at a constant level for 90 days in the absence of tumorigenesis | Two different labels which are used to detect the 2 cell types; not able to compare their detection efficiencies due to different sensitivities | [28] |
MSC and IGF -I gene-enhanced MSC 10 × 106 in 1 ml | – | 8 weeks | Evaluated for biochemical composition and mechanical test; collagenase-induced lesions | No different effect between both of cells | Cons: optimal dose of MSCs, extended IGF-I expression and less viral vectors for IGF-I delivery should be investigated | [29] |
Tenogenic induction allogeneic Pb-MSCs 2–3 × 106 in 1 ml | PRP | 2 years | Safety and clinical efficacy for 6 week; long-term efficacy of a combination of PRP and MSCs to treat natural tendon injury | No adverse effect; no calcification; low re-injury rate after 2 years (18% vs 44%) | Cons: no control groups were included; veterinary practitioners for scoring were not blinded | |
TSPCs 5 × 106 in 0.15 ml at 2 sites (1 × 107 cells in total) | – | 16 weeks | Evaluate the efficacy of autogenous TSPC injections in a collagenase-induced model injury | Improved the tensile strength and collagen fiber alignment | Cons: long-term effect of TDPCs on the biomechanical properties will be determined | [32] |