Table 2.
Summary of pre-clinical studies using bone marrow mesenchymal stem cells
|
Ref.
|
Animal/model
|
Cell/cell number
|
Method of delivery
|
Control
|
Outcome measurement/timeline
|
| Lim et al[52], 2004 | Rabbit/Bilateral ACL reconstructions using hamstring tendon autografts | BMSC/3-4 × 106 | Grafts were coated with BMSCs in a fibrin glue carrier | ACL reconstruction without BMSCs | Histology, biomechanics/2, 4, and 8 wk |
| Ouyang et al[53], 2004 | Rabbit/The hallucis longus tendons were translated into calcaneal bone tunnels | BMSCs/× 107 | BMSCs immobilized in fibrin glue were injected in the bone tunnel | Translation without BMSCs | Histology, immunohistochemistry/2, 4, and 6 wk |
| Soon et al[54], 2007 | Rabbit/Bilateral ACL reconstructions using Achilles tendon allografts | BMSCs/4 × 106 | Grafts were coated with BMSCs in a fibrin glue carrier | ACL reconstruction without BMSCs | Histology, biomechanics/2, 4, and 8 wk |
| Gulotta et al[60], 2009 | Rat/Unilateral detachment and repair of the supraspinatus tendon | BMSC/× 106 | BMSCs were pelleted down and mixed with fibrin sealant for implantation | Rotator cuff repair without BMSCs | Histology, biomechanics, cell tracking/2, 4 wk |
| Nourissat et al[57], 2010 | Rat/Destructing the enthesis of the Achilles' tendon and attaching the tendon back to the calcaneum | BMSCs/4 × 106, chondrocytes/4 × 106 | Cells were injected at the site of repair | Defect without cells | Histology, immunohistochemistry, biomechanics/15, 30, and 45 d |
| Li et al[56], 2011 | Rat/The isolated flexor digitorum longus tendon were translated into tibia bone tunnels | BMSCs/5 × 106 | BMSCs were injected into the tendon-bone interface | Translation without BMSCs | Biomechanics, cell tracking/2, 4, and 8 wk |
| Kida et al[16], 2013 | Rat/Bilateral detachment and repair of the supraspinatus tendon | BMSCs/- | Drilling into the bone marrow was performed in the greater tuberosity | Rotator cuff repair without drilling | Histology, biomechanics, cell tracking/2, 4, and 8 wk |
| Kanazawa et al[61], 2014 | Rabbit/Bilateral ACL reconstruction without a tibial bone tunnel using semitendinosus tendon autografts | BMSCs/× 106 | BMSCs with the collagen sponge or a fibrin sealant were transplanted between the bottom of the grafted tendon and the bone pit of the tibia | ACL reconstruction without BMSCs | Histology, immunohistochemistry/4 and 8 wk |
| Teng et al[62], 2016 | Rabbit/Unilateral ACL reconstructions using hamstring tendon autografts | BMSCs/× 107 | Graft wrapped with PRP and BMSCs in fibrin glue and secured to the periosteum by surgical | ACL reconstruction without BMSCs | Histology, biomechanics, RT-PCR, micro-CT scan/4 and 8 wk |
| Degen et al[58], 2016 | Rat/Unilateral detachment and transosseous repair of the supraspinatus tendon | Human BMSCs/106 | BMSCs placed at the tendon-bone interface with fibrin glue | Rotator cuff repair without BMSCs | Histology, biomechanics/2 and 4 wk |
| Setiawati et al[64], 2017 | Rabbit/Unilateral ACL reconstructions using semitendinosus tendon autografts | Rabbit BMSCs/2 × 106 with 100 μg VEGF | BMSCs were injected into the bone tunnel | ACL reconstruction without BMSCs | Biomechanics, immunohistochemistry, MRI/3 and 6 wk |
| Thangarajah et al[65], 2018 | Rat/Unilateral detachment and transosseous repair of the supraspinatus tendon | BMSCs/106 | BMSCs + DBM placed on the decorticated humeral head with fibrin glue | Rotator cuff repair without DBM | Histology, cell tracking, pqCT/6 wk |
| Lu et al[59], 2019 | Rat/The isolated flexor digitorum longus tendon were translated into tibia bone tunnels | BMSCs/106 | BMSCs were injected into the tendon-bone interface | Translation without BMSCs | Histology, immunohistochemistry, biomechanics/2 and 6 wk |
| Liu et al[67], 2019 | Dog/Unilateral full-thickness infraspinatus tendon injury was created | BMSCs/106 | Detached tendon was sandwiched between the two tendon layers of TFBC and one BMSCs sheet seeded on the tendon interfaces | Rotator cuff repair without BMSCs | Histology, biomechanics/6 wk |
| Hur et al[55], 2019 | Rabbit/Unilateral ACL reconstructions using extensor digitorum longi tendon autografts | BMSCs/1.0 -1.5 × 107 | BMSCs embedded in fibrin glue was injected to the end of graft | ACL reconstruction without BMSCs | Histology, micro-CT/12 wk |
| Han et al[63], 2019 | Rat/Unilateral detachment and repair of the supraspinatus tendon | BMSCs/- | - | Rotator cuff repair without BMSCs | Histology, biomechanics, RT-PCR/4 and 8 wk |
| Huang et al[71], 2020 | Rat/Unilateral detachment and reconstruction of the supraspinatus tendon | BMSC-Exos/200 μg | BMSC-Exos were injected into the tail vein | Rotator cuff repair with PBS | Histology, immunohistochemistry, biomechanics, RT-PCR, micro-CT/4 and 8 wk |
| Shi et al[70], 2020 | Mice/Destructing the enthesis of the Achilles' tendon and attaching the tendon back to the calcaneum | BMSC-Exos/- | Exos mixed with hydrogel and implantation in the mice | Defect without Exos | Histology, immunohistochemistry, biomechanics, RT-PCR/7, 14, and 30 d |
BMSC: Bone marrow mesenchymal stem cell; ACL: Anterior cruciate ligament; MRI: Magnetic resonance imaging; pqCT: Peripheral quantitative computed tomography; DBM: Demineralized bone matrix; RT-PCR: Reverse transcription polymerase chain reaction; RT-qPCR: Reverse transcription quantitative polymerase chain reaction; TFBC: Tendon-fibrocartilage-bone composite; Exos: Exosomes; PBS: Phosphate-buffered saline.