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Table 1 Summary of in vivo studies of cell therapy for tendon injury in horse

From: Strategies of tenogenic differentiation of equine stem cells for tendon repair: current status and challenges

Cell source and injected cell number Supplement Follow-up Evaluation Observation Pros/cons Reference
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]
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]
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]
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]
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]
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 [23, 24]
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]
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 [26, 27]
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 [30, 31]
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]
  1. Abbreviations: BM-MSCs bone marrow-derived mesenchymal stem cells, ASCs adipose tissue-derived MSCs, ESCs embryonic stem-like cells, ADNC adipose-derived nucleated cell, TSPCs tendon-derived progenitor cells, PC platelet concentrate, Pb-MSCs peripheral blood-derived mesenchymal stem cells, oAECs ovine amniotic epithelial cells, COMP cartilage oligomeric matrix protein, COL3 collagen type III, COL1 collagen type I, TNMD tenomodulin, TNC tenascin-C