Table 1.
Enzymatically derived ADSC/SVF in animal model tendinopathy and tendon injury.
| Authors | Animal Model | Injury | ADSC-SVF Provenience | Treatment | Investigation | Outcomesx |
|---|---|---|---|---|---|---|
| Lee et al. [34] |
Sprague Dawley rats-in vivo | Full thickness Achilles tendon defect | Human subcutaneous fat tissue | Group 1: fibrin glue-ADSC injection Group 2: fibrin glue Group 3: control group |
Histological Immunohistochemical, Biomechanical, Proteomic evaluation | Better gross morphological and biomechanical recovery in ADSC group. Increased expression of HST-C1 and T-1. |
| Oshita et al. [21] |
16 F344/NSIc rats | Collagenase iatrogenic Achilles tendon injury | inguinal fat pads of two F344/NSlc rats | Group 1: ADSC injection Group 2: saline injection |
Histological Immunohistochemical | ADSC group decreased levels of disrupted collagen fibers, cellularity, and hypervascularity. Increased expression COL1, decreased expression COL3. |
| De Aro et al. [35] | Lewis rat | Transected Achilles tendon | Inguinal region of 10 male Lewis rats | Group 1: untreated Group 2: ADSC Group 3: GDF-5 Group 4: ADSC + GDF-5 |
Biomechanical, RT-PCR |
The ADSC increased expression of Lox, Dcn, and Tgfb1. Lower deformation at higher stress. |
| Chen et al. [36] |
Sprague-dawley rats | Collagenase induced rotator cuff injury | Human subcutaneous fat tissue | Group 1: untreated Group 2: ADSC |
Histological, RT-PCR, Biomechanical |
Improvement in collagen fibres alignment, increased COL1, TNC expression No biomechanical differences at final endpoint |
| Valencia Mora et al. [37] | Sprague-Dawley rats | Detachment and repair of the supraspinatus tendon | Rat subcutaneous fat tissue | Group 1: collagen carrier Group 2: collagen carrier + ADSC Group 3: untreated |
Biomechanical Histological | ADSC group showed less acute inflammation signs. No significative differences in biomechanical analysis. |
| Shen et. al. [38] | Mongrel Dogs | Second and fifth flexor digitorum profundus (FDP) zone II tendon transection and repair | Autologous subcutaneous fat tissue+ collagen sheet | Group 1: ADSC + collagen sheet wraps around the tendon Group 2: HA Group 3: suture only |
Gene expression Immunostaining Histological |
ADSC modulated the inflammatory phase of tendon healing, promoted a regenerative/anti-inflammatory M2 macrophage phenotype and influenced tendon extracellular matrix remodeling, angiogenesis, and cell survival. |
| Canapp et al. [39] | Dogs | Supraspinatus tendinopathy | Autologous subcutaneous fat tissue+PRP | Group 1: ADSC + PRP peritendinous injection by US guidance Group 2: contralateral non-affetcted |
MRI, US, XR evaluation; Gait analysis |
TPI significant increase in Treated limb |
| Vieira et al. [40] | New Zeland Rabbits | Achilles tendon cut injury | Autologous subcutaneous adipose tissue | Group 1: tendon cut Group 2: tendon suture Group 3: tendon suture + ADSC |
Histological Analysis | Increase of vascular score and collagen fibres structural organization in Group 2 and 3 |
| Chen et al. [41] | New Zeland Rabbits | Achilles tendon cut injury | Autologous subcutaneous adipose tissue | Group 1: tendon cut and sutured Group 2: tendon cut and sutured + ADSC |
Cell viability, histological, proteomic analysis Biomechanical analysis |
Increased tenocyte viability in ADSC group, mechanical strength and increased expression of TM BG Dcn |
| Uysal et al. [42] | Japanese rabbits | Achilles tendon cut injury | Autologous subcutaneous adipose tissue | Group 1: PRP gel Group 2: PRP + ADSC |
Histological immunohistochemical, biomechanical analysis | COL1 FGF VEGF higher in ADSC treated group. Tgfb lower. Higher tendon tensile strength in ADSC treated group. |
| Lu et al. [43] | New zeland rabbits | Supraspinatus tendon incision and suture | Autologous subcutaneous adipose tissue | Group 1: ADSC-FG Group 2: FG |
Histological, immunohistochemical, biomechanical analysis, MRI analysis | Higher expression of COL1, and ratio of COL3/COL1. Higher biomechanical value in ADSC-FG group, MRI better results after 12 weels |
| Behfar et al. [28] | New zeland rabbits | Deep digital flexor tendon transection and sutured. | Autologous subcutaneous adipose tissue | Group 1: tendon suture Group 2: tendon suture + ADSC |
Histological, immunohistochemical, biomechanical analysis | Higher orientation of collagen bundles and fibrillar continuity. Increased expression of COL1. Higher tensile strength parameters. |
| Behfar et al. [44] | New zeland rabbits | Deep digital flexor tendon transection and sutured. | Autologous subcutaneous adipose tissue | Group 1: tendon suture Group 2: tendon suture + ADSC |
biomechanical analysis | Significant increases in ultimate and yield load, energy absorption, and stress were noted at both time points when treatment groups were compared to their matched controls |
| Geburek et al. [45] | Warmbloods and trotter horses | Superficial digital flexor tendon surgical core lesion | Autologous subcutaneous adipose tissue | Group 1: inactivated autologous serum Group 2: ADSC injection |
Histological, immunohistochemical biomechanical, clinical, US examination |
No differences in histological findings, no difference in GAG, biomechanical, US results. |
| Carvalho et al. [46] | Mixed breed horses | Superficial digital flexor tendon collagenase iatrogenic injury | Autologous subcutaneous adipose tissue | Group 1: control Group 2: ADSC injection |
Flow cytometric peripheral blood fluorescent microscopy | Cell presence, nanocrystals valuable in vivo markers |
| Conze et al. [47] | Warmblood and standardbreed horses | superficial digital flexor tendon surgical core lesion | Autologous subcutaneous adipose tissue | Group 1: control Group 2: ADSC injection |
Histological, immunohistochemical, US analysis | Histology staining significantly higher for new vessels and FVIII. More vascularization in us doppler control. |
| Polly et al. [48] | Mixed breed horses | Superficial digital flexor tendonitis | Autologous subcutaneous adipose tissue | Group1: control Group2: ADSC co-cultured |
Genic expression analysis | Significantly higher expression of IGF1, Tgfb1, SDF1. Lower expression of COMP. |
Adipose-Derived Stem Cell (ADSC); Stromal Vascular Fraction (SVF); Human-specific Type I collagen (HST-C1); Tenascin-1(TNC); Collagen Type 1 (COL1); Collagen Type 3 (COL3); Growth differentiation factor-5 (GDF-5); Real Time-PCR (RT-PCR); Lysyl oxidase (Lox), Decorin (Dcn); Transforming growth factor, beta 1 (Tgfb1); Hyaluronic Acid (HA); Platelet Rich Plasma (PRP); Ultrasound (US); Magnetic Resonance Imaging (MRI); X-rays (XR); Cross Sectional Area (CSA); Total Pressure Index (TPI); Tenomodulin (TM); Biglycan (BG); Fibroblast Growth Factor (FGF); Vascular Endothelial Growth Factor (VEGF); Fibrin glue (FG); Glycosaminoglycan (GAG); Factor VIII(FVIII); Insulin like growth factor1 (IGF1); SDF1 Stromal derived factor1 (SDF1); Cartilage Oligomeric Matrix Protein (COMP).