Table 2.
Clinical studies using stem/progenitor cells, growth factors or their combination for rotator cuff repair.
| Cell type/Growth factor | Study type/Level of evidence | Tear size | Sample size | Method of delivery | Follow-up period | Clinical outcome | Ref. |
|---|---|---|---|---|---|---|---|
| Stem/Progenitor Cells | |||||||
| BMSCs | Cohort/3 | Full-thickness | 124 (57/67) | Drilling into the bone marrow was performed in the greater tuberosity. | At a minimum of 2 years | No significant difference in pain, range of motion, strength, overall satisfaction and functional scores. The retear rate was significantly lower. | Jo et al., 2013 [120] |
| BMSCs | Case-controlled/4 | Tear size from 1.5 to 3.5 cm | 90 (45/45) | BMSCs were injected into the tendon-bone interface. | At a minimum of 10 years | Enhanced healing rate, improved quality of the repaired surface, reduced number of recurrent defects. | Hernigou et al., 2014 [121] |
| BMSCs | Retrospective cohort/3 | Full-thickness | 111 (67/44) | Drilling into the bone marrow was performed in the greater tuberosity. | 2–24 months | Improved cuff repair integrity and lower retear rate in large-massive tears. | Taniguchi et al., 2015 [206] |
| ADSCs | Cohort/3 | Full-thickness | 70 (35/35) | Injection of adipose-derived MSCs loaded in fibrin glue during rotator cuff repair. | 28.3 ± 3.8 months | No clinical differences in the 28-month period of follow-up compared to the conventional group. | Kim et al., 2017 [122] |
| Growth Factors | |||||||
| PRP | Randomized controlled trial/1 | Subacromial impingement syndrome/partial-thickness | 60 (30/30) | Injection of autologous PRP into the subacromial bursa. | At a minimum of 2 years | No improvement for clinical outcomes. May have potential deleterious effects on healing tendons. | Carr et al., 2015 [153] |
| PRP | Randomized controlled trial/1 | Medium-sized to large cuff tear | 102 (52/50) | Delivery of autologous PRP over the cuff surface through the arthroscopic portal. | At a minimum of 2 years | Visual analog scale scores were lower at 1, 3 and 6 months; Constant-Murley scores improves at 12 and 24 months; UCLA acores were higher at 6 and 12 months; Retear rate decreased at 24 months for large tears. | Pandey et al., 2016 [152] |
| PRP | Randomized controlled trial/1 | Complete rotator cuff tear | 120 (60/60) | Intraoperative pure PRP injection. | 6 and 24 months | No significantly improved function at 3, 6, and 24 months. | Flury et al., 2016 [207] |
| PRP | Randomized controlled trial/1 | Full-thickness | 60 (30/30) | Injection of autologous PRP. | 12 months | Lower recurrence rates. | Zhang et al., 2016 [151] |
| PRP | Randomized controlled trial/2 | Complete supraspinatus tear | 51 (26/25) | Liquid PRP prepared by apheresis with autologous thrombin was applied in the tendon-to-bone interface. | 60 months | No improvement for clinical or structural results at 60-month follow-up. | Malavolta et al., 2018 [148] |
| LR-PRP | Prospective randomized therapeutic trial/2 | Rotator cuff tear | 87 | Ultrasound guided injection of leukocyte-rich PRP. | 12 months | No improvement by patient-reported outcome measures and Constant score at 1 year postoperatively. | Snow et al., 2020 [147] |
| rhBMP-12 | Randomized controlled trial/2 | Full-thickness (2–4 cm wide) | 20 (16/4) | rhBMP-12/absorbable collagen sponge (ACS) was applied to the footprint. | 12 months | Functional recovery in theVAS score for pain,ROM, and isometric strength was similar compared to the control group | Ide et al., 2017 [138] |
| Combination of Stem/Progenitor Cells and Growth Factors | |||||||
| Subacromial bursa, cBMA, PRP | Therapeutic case series/4 | Tears with at least 2 tendons | 16 | Arthroscopic rotator cuff repair augmented using subacromial bursa, cBMA, and platelet-rich plasma delivered to the injury site. | 12.6 ± 1.8 months (range 12–19 months) | Improvement in ASES, Constant-Murley, SANE and pain scores. | Muench et al., 2020 [208] |