Table 3.
Characteristics of animal models.
| Article | Method of Delivery | Animal Model | Number Used | Animal Age | Animal Weight | Animal Gender | Follow-up | Number per Experimental Group |
|---|---|---|---|---|---|---|---|---|
| Shi et al. [25] | 10 µL of fibrin containing 25 µg BMSC-EVs was applied around the injury site. | Sprague–Dawley rats Central 1/3 of patellar tendon was removed from the distal apex of the patella to the insertion of the tibial tuberosity. |
48 | N/A | N/A | Male | 2 weeks (immunohistochemistry analysis) 4 weeks (histological analysis) |
(1) BMSC-EVs group (n = 16) (2) Fibrin group (n = 16) (3) Control group, left untreated (n = 16) |
| Shen et al. [26] | ASC-EVs were loaded to the surface of a collagen sheet, that was cut into strips, each containing 5–6 × 109 EVs. Applied around the defect site. | NGL transgenic reporter mice. Right Achilles tendon 2/3 transection at midpoint level between calcaneal insertion and musculotendinous junction. |
32 | 3–4 months | 27 ± 5 g | Male and female | 7 days | (1) Collagen sheet loaded with EVs from naïve ASCs (n = 11) (2) Collagen sheet loaded with EVs from IFNγ-primed ASCs (n = 10) (3) Collagen sheet only (n = 11) |
| Yu et al. [27] | 5 µL of BMSCs-exos (4 µg/µL) was mixed with 1 µL thrombin (500 IU/mL) and 4 µL fibrinogen (50 mg/mL), injected into the defect site. | Sprague–Dawley rats Central 1/3 of the patellar tendon (0.8 mm in width) was removed from the distal apex of the patella to the insertion of the tibial tuberosity. |
52 | Adult | 200 g | Male | 1 week, 2 weeks, and 4 weeks (macroscopic and histological examination) 4 weeks (mechanical test) |
(1) Fibrin-exos (fibrinogen, thrombin, and exosomes injected) (n = 26) (2) Fibrin-vehicle (fibrinogen, thrombin, and PBS injected) (n = 26) |
| Shi et al. [28] | Exosomes were mixed with hydrogel before implantation into the cut Achilles tendon. | C57BL/6 mice. The Achilles tendon was cut off above the calcaneus. |
90 | 8 weeks | 20–25 g | Male | 7 days | (1) Control group (n = 30) (2) Hydrogel group (n = 30) (3) Hydrogel + exosome group (n = 30) |
| Gissi et al. [29] | 50 μL of PBS was injected locally with either EVL (2.8 × 1012) or EVH (8.4 × 1012). | Lewis mice. Bilateral Achilles tendon defect 2 mm in diameter was made in each animal. |
16 | Adult | 180–200 g | Male | 30 days | (1) PBS alone (control group) (n = 4) (2) rBMSCgroup: 4 × 106 cells (n = 4) (3) EVL group: 2.8 × 1012 EVs (n = 4) (4) EVH group: 8.4 × 1012 EVs. (n = 4) |
| Yao et al. [30] | Injected subcutaneously around injury site with HUMSC-Exos (200 μg) dissolved in PBS and an equal volume of PBS (50 μL). | Sprague-Dawley rats. The Achilles tendon was cut in the middle. |
60 | Adult | 200–250 g | Male | 3 weeks | (1) Sham group (n = 20) (2) HUMSC-Exos group (n = 20) (3) PBS group (n = 20) |
| Chamberlain et al. [31] | Injected 1 × 109 exosomes to MCL transection site. | Wistar rats Bilateral MCL transection at its midpoint. |
10 | Adult | 300–350 g | Male | 14 days | (1) Exosomes (n = 5) (2) PBS (control) (n = 5) |
| Huang et al. [32] | 200 μg of BMSC-Exos precipitated in 200 μL of PBS was injected into the tail vein. | Sprague-Dawley rats. 2 mm of the distal tendon of the supraspinatus was cut off. |
54 | 4 weeks | 70–100 g | Male | 4 weeks | (1) BMSC-Exos group (n = 27) (2) PBS (control) (n = 27) |
| Li et al. [33] | HCPT-EVs were both subcutaneously injected at the injury site at a dose of 200 μg. | 33 Sprague-Dawley rats The Achilles tendon was transected in the middle and repaired using the 6-0 polypropylene suture. |
33 | Adult | 250–300 g | Male | 3 weeks | (1) PBS (n = 11) (2) Unprimed EV injection (n = 11) (3) HCPT-EV injection (n = 11) |
| Wang et al. [34] | 20 μL of exosomes (486.3 μg/mL) was injected into the Achilles tendon injury site twice a week. | 18 male Sprague-Dawley rats Rats were injected with 30 µL type I collagenase solution (10 mg/mL) into both Achilles tendons. |
18 | 8 weeks | 200–250 g | Male | 4 weeks | (1) PBS (control) (n = 6) (2) Injury group with TSCs (n = 6) (3) Injury group with exosomes (n = 6) |
| Wang et al. [35] | 1011 ASC-Exos suspended in 20 µL of saline were injected at the injury site of the supraspinatus muscle. | Rabbits: Bilateral rotator cuff tear model. The supraspinatus tendon was detached at the insertion on the humerus. The torn tendon was wrapped with a silicon Penrose drain to prevent adhesion. |
35 | 4 months | 3.3 ± 0.3 kg | Male | 18 weeks | (1) Repair + saline (n = 7) (2) Repair + ASC-Exos (n = 7) (3) Sham surgery (n = 14) (4) Fatty infiltration assay (n = 7) |
EVs = extracellular vesicles; MSC = mesenchymal stem cells; BMSC = bone marrow-derived multipotent mesenchymal stromal cells; rBMSCs = rat bone marrow-derived MSCs; ASCs = adipose-derived mesenchymal stem cells; PBS = phosphate-buffered saline; HUMSC = human umbilical mesenchymal stem cells; NGL = NF-κB-GFP-luciferase; HCPT = hydroxycamptothecin.