Table 1.
Included studies characteristics
| ID | Study (first author, year) | Study design | Type and Site of injury | Groups | Population | Cell type | Cell source | Follow up | Surgical techniques | Conclusion | Level of evidence |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Rotator cuff | |||||||||||
| 1 | Ellera Gomes 2011 | Case-series | Complete rotator cuff tear (Open surgical repair + injection BMMC) |
BMMC group (N = 14) no control group |
14 | Autologous BMMC |
BMMC (from the posterior iliac crest) |
12 months | Open surgical repair | BMMC implantation in a patient with rotator cuff sutures is safe and has promising results compared to historical data (patients underwent surgical procedures without stem cells application). | 4 |
| 2 | Hernigou P 2014 | Non-RCT | Rotator cuff tear with size of 1.5-3.5 cm (Arthroscopic surgical repair + MSCs) |
1. MSC group (N = 45) 2. Control group (N = 45) |
90 (45 each groups) | Autologous MSC | BMC (from anterior iliac crest bone) | 10 years< | Arthroscopic surgical repair | More prominent and earlier (2 months earlier, p = 0.04) healing in MSC-treatment group, total healing more likely achieved when MSCs> 2500 cell.mL−1 | 3 |
| 3 | C. J. Centeno 2015 | Case series | Partial or full-thickness rotator cuff tear (< 1.5 cm) | BMC + PRP + PL (N = 102 patients with 115 involved shoulders which N = 81 arm with rotator cuff tear) | 81 | Autologous MSC | BMC (from posterior superior iliac crest) | 11.2 ± 10 months | No surgery | Rotator cuff tear patients treated with BMC showed significant pain and functional improvement | 4 |
| 4 | Kim, Y. S 2017 | Non-RCT | full-thickness rotator cuff tear (AD-MSC + Arthroscopic surgical repair) |
1. Arthroscopic rotator cuff repair alone group (N = 35) 2. AD-MSC group + arthroscopic repair (N = 35) |
70 (35 each groups) | Autologous AD-MSC | Buttock fat pad | 28.3 ± 3.8 months | Arthroscopic rotator cuff repair | AD-MSC injection along with rotator cuff repair reduce retear rate significantly, but no clinical differences at the end of the follow up comparing to controls | 3 |
| 5 | S. J. Kim 2017 | Case-series | Partial rotator cuff tear |
BMC + PRP group (N = 12) No control group |
12 | Autologous MSC | BMC (from anterior iliac crest bone) | 3 months | No surgery | Injection of BMC–PRP to the rupture site leads to improvement of the reduction of the clinical symptoms of tear size. | 4 |
| 6 | S. J. Kim 2018 | Non-RCT | Partial tear of the rotator cuff tendon |
1. BMC + PRP group (N = 12) 2. Physical therapy (N = 12) |
24 (12 each groups) | Autologous MSC | BMC (from anterior iliac crest bone) | 3 months | No surgery | BMC-PRP injection improve VAS and ASES scores (improve pain and shoulder function), tear size changes, and MMT did not statistically differ among groups | 3 |
| 7 |
J. R. Lamas 2019 (It was stopped due to adverse effects in both groups.) |
RCT | Full-thickness rotator cuff tear |
1. BM-MSCs + type I collagen membrane (OrthADAPT™) (N = 8) 2. Only type I collagen membrane (N = 5) |
13 (8 intervention group and 5 controls) |
Autologous BM-MSC | BMC (right posterior superior iliac spine) | 12 months | Arthroscopic rotator cuff repair | The authors of the study decided to terminate the study prematurely because four patients experienced postoperative complications. A re-rupture was observed in 3/5 control subjects (60%) and in 5/8 treatment subjects (62.5%). The complications experienced by both study groups could not be related to the autologous MSCs but to the scaffold (OrthADAPTTM). However, the Constant score was significantly higher in the treatment group (p = 0.007). | 1 |
| 8 | Hurd, J. L 2020 | RCT | Partial-thickness rotator cuff tears |
1. UA-ADRCs (N = 11) 2. Methylprednisolone (N = 5) |
16 (11 intervention group and 5 controls) |
unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) | Periumbilical abdominal area, bilateral flanks, or medial thigh | 13 months | No surgery | UA-ADRCs application in sPTRCT patients is safe and significantly improved function of the shoulder compared to the control group, with no side effects. | 1 |
| 9 | C. H. Jo 2020 | Case series | Partial-thickness rotator cuff tear |
1. AD-MSC Low dose (N = 3) 2. AD-MSC Mid dose (N = 3) 3. AD-MSC High dose (N = 13) With no control group |
19 | Autologous AD-MSCs | Abdominal subcutaneous fat | 24 months | No surgery | Intratendinous injection of AD-MSCs is a safe and effective treatment for partial tears of rotor cuff | 3 |
| 10 | L. N. Muench 2020 | Case series | Rotator cuff tear (Arthroscopic rotator cuff repair) | Arthroscopic rotator cuff repair + BMC + PRP + subacromial bursa (N = 16) | 16 | Autologous BMC | BMC (from proximal humeral head) | 12.6 ± 1.8 (12<) months | Arthroscopic rotator cuff repair | This study showed that arthroscopic rotator cuff repair augmented with BMC improves patient function | 4 |
| Elbow | |||||||||||
| 11 | D. Connell 2009 | Case series | Refractory lateral epicondylitis (tennis elbow) |
Elbow CEO tendinosis group (N = 12) without control group |
12 | Autologous tenocyte-like cell (derived from dermal fibroblast) | Skin | 6 months | No surgery | Tendon like cells have a therapeutic effect on refractory CEO tendinosis | 4 |
| 12 | A. Singh 2014 | Case series | Previously untreated Lateral epicondylosis (tennis elbow) |
Elbow CEO tendinosis BMC injected group (N = 26) without control group |
Autologous MSC | BMC (from anterior-superior iliac spine) | 3 months | No surgery | significant improvement of pain relief and recovery from the disease following a single injection of BMC | 4 | |
| 13 | A. Wang 2015 | Case series | Severe refractory Lateral Epicondylitis (tennis elbow) | Tenocytes injection (N = 15) | 15 | Autologous Tenocytes | Patellar tendon | 4.5 years (range, 3.1-5.2) | No surgery | Tenocyte injection for Lateral Epicondylitis treatment showed acceptable results in function and structure improvement. | 4 |
| 14 | Lee, S. Y 2015 | Case series | Chronic and intractable Lateral epicondylosis (tennis elbow) |
1. AD-MSC low dose (N = 6) 2. AD-MSC high dose (N = 6) no control group |
12 (6 each groups) | Allogenic AD-MSC | Human subcutaneous fat tissue | 13 months | No surgery | Allogenic AD-MSC injection for lateral epicondylosis treatment is safe and effective. | 4 |
| 15 | M. Khoury 2021 | Case series | Chronic, recalcitrant lateral elbow tendinopathy (LET) |
AD-MSC (N = 18) no control group |
18 | Autologous AD-MSC | Periumbilical zone | 6 months | No surgery | Recalcitrant LET in tennis players showed clinical improvement and anatomical repair after autologous ASCs injection. | |
| Achilles | |||||||||||
| 16 | K. Tate-Oliver 2013 | Case- series | Achilles tendinosis and interstitial tears (N = 3) |
1. HD-PRP + AD-tSVF (N = 2) 2. HD-PRP + AD-tSVF + BMC (N = 1) |
3 |
Autologous adipose graft (AD-tSVF) plus additive of HD-PRP |
Lower abdomen-flank area (male and female) or lateral thigh-buttock area (females) |
3-4 years | No surgery | Use of AD-SVF and HD-PRP and/or BMAC is safe and a good option for Achilles tendonitis management without surgery | 4 |
| 17 | Stein, B. E 2015 | Case-series | Sport-related Achilles tendon tear (open repair + BMC) |
BMC injection group (N = 27) No control group |
27 | Autologous MSC | BMC | 29.7 ± 6.1 months | open repair | Patient with Achilles tendon repairs treated with BMAC injection shows a great functional rate of return to sport, rehabilitation progress, and single-limb heel raise outcomes. | 4 |
| 18 |
Usuelli, F. G 2017 |
RCT | Recalcitrant non-insertional Achilles tendinopathy |
1. PRP group (N = 23) 2. SVF group (N = 21) |
44 (21 intervention group and 23controls) | Autologous Adipose-derived SVF | Subcutaneous adipose tissue | 6 months | No surgery | We can use both PRP and SVF to treat recalcitrant Achilles tendinopathy, and it’s safe and effective. However, we can obtain results faster in SVF treatment. | 1 |
| Patellar | |||||||||||
| 19 | A. W. Clarke 2011 | RCT | Refractory patellar tendinosis |
Patellar tendinopathy (N = 60, in 46 patients) 1. Plasma-only injection group (N = 27) 2. Tenocyte-like Cell + plasma injection group (N = 33) |
60 knees (46 patients, 33 in the intervention group) | Autologous skin-Derived Tenocyte-like Cells | Skin | 6 months | No surgery | Patellar tendinopathy treated with skin-derived tendon-like cells can be safely treated in the short term, with a significantly better outcome than that achieved with plasma alone. | 1 |
| 20 | C. Pascual-Garrido 2012 | Case series | Chronic patellar tendinopathy |
BM-MNC group (N = 8) No control group |
8 | Autologous BM-MNC | BMC (from anterior iliac crest bone) | 5 years (range, 3–6) | No surgery | BM-MNC therapy improves chronic patellar tendinopathy after nonoperative treatment’s failure | 4 |
| 21 | G. Rodas 2021 | RCT | Initial, unilateral, chronic patellar tendinopathy with an intratendinous lesion > 0.3 mm |
1. Lp-PRP group (N = 10) 2. MSC group (N = 10) |
20 (10 each groups) | Autologous BM-MSC | Bone marrow | 12 months | No surgery | This study confirmed that treatment with BM-MSC or Lp-PRP could reduce the pain; however, BM-MSC is more effective | 2 |
| Gluteal | |||||||||||
| 22 | D. A. V. Rosário 2021 | RCT | Gluteal tendinopathy |
1. Corticosteroid group (N = 25) 2. BMC group (N = 15) |
40 (15 intervention group and 25 controls) | Autologous MSC | BMC | 6 months | No surgery | This study approve that BMAC is safe and effective to treat gluteal tendinopathy | 2 |
Abbreviations: BMC Bone marrow concentrate, PRP Platelet-rich plasma, VAS Visual analog scale, MMT Manual muscle test, ASES American Shoulder and Elbow Surgeons, NSAID Non-steroidal anti-inflammatory drugs, BM-MNC Bone marrow mononuclear cell, IKDC International knee documentation committee, KOOS Knee injury ad osteoarthritis outcome score, SF12 Short Form-12, ADL Activities of daily living, QOL Quality of life, AD-MSC Adipose-derived MSC, EGF Epidermal growth factor, SPADI Safety and the shoulder pain and disability index, NCI – CTCAE v4.0 National Cancer Institute - Common Terminology Criteria for Adverse Events version 4.0 scale, AE Adverse event, PRTEE Patient-Rated Tennis Elbow Evaluation, IQR Interquartile range, RCT Randomized controlled trial, CEO Common extensor origin, KSS Knee Society Score, OA Osteoarthritis, PL Platelet lysate, DASH Disabilities of the arm, shoulder and hand, NPS Numeric pain scale, MCID Minimal clinically important difference, UCLA University of California, Los Angeles, MEPI Modified Mayo clinic performance index for the elbow, TEAEs Treatment emergent adverse events, VISA Victorian Institute of Sport Assessment, sPTRCT Symptomatic, partial-thickness rotator cuff tears, UA-ADRC Uncultured, unmodified, autologous adipose-derived regenerative cell, SVF Stromal vascular fraction, BMMC Bone marrow mononuclear cells, US Ultrasound, HD-PRP High-density platelet rich plasma, AD-tSVF Autologous adipose-derived tissue stromal vascular fraction, Lp-PRP Leukocyte-Poor Platelet-Rich Plasma, SANE Single Assessment Numerical Evaluation, UA-ADRCs Unmodified, autologous adipose-derived regenerative cells, UEFS Upper Extremity Functional Scale