Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review
Abstract
:1. Introduction
2. Methods
2.1. Eligibility Criteria
2.2. Information Sources and Search Strategy
2.3. Study Selection and Data Collection Process
2.4. Data Items and Quality Assessment
3. Results
3.1. Study Design and Methods
Reference | Study | Diagnosis of Tendinopathy | Adipose Tissue | Cell Fraction from Adipose Tissue | Treatment | Final Follow-Up and Relative Outcomes |
---|---|---|---|---|---|---|
Kim et al. 2017 [55] | Cohort study (Korea) | Rotator cuff disease (MRI) | Lipoaspirated autologous adipose tissue from buttocks, enzymatically digested | ASCs | Intratendinous injections of ASCs (4.46 × 106 cells) during arthroscopic rotator cuff repair | 28 months VAS ROM Constant score UCLA score MRI |
Jo et al. 2018 [56] | First-in human trial (Korea) | Rotator cuff disease (MRI) | Lipoaspirated autologous abdominal subcutaneous adipose tissue, enzymatically digested | ASCs | Ultrasound-guided intratendinous injection of 3 mL of ASCs at low-(1.0 × 107 cells), mid-(5.0 × 107) and high-dose (1.0 × 108) | 6 months SPADI Constant score VAS MRI |
Usuelli et al. 2018 [58] | Randomized clinical trial (Italy) | Unilateral or bilateral chronic Achilles tendinopathy (MRI, US) | Lipoaspirated autologous abdominal subcutaneous adipose tissue, processed with Fasti kit System | ASCs in SVF | Ultrasound-guided intratendinous injection of 4 mL of SVF (1.0 × 108) | 6 months VAS AOFAS VISA-A SF-36 MRI |
Lee et al. 2015 [57] | Open-label study (Korea) | Chronic lateral epicondylosis (US) | Lipoaspirated allogeneic human subcutaneous adipose tissue, enzymatically digested | allo-ASCs | Ultrasound-guided intratendinous injection of in 1 mL allo-ASCs (106 or 107 cells) mixed with fibrin glue | 13 months VAS MEPI US |
Khoury et al. 2021a [59] | Prospective longitudinal case series exploratory study (Argentina) | Chronic insertional patellar tendinopathy (MRI) | Lipoaspirated autologous adipose tissue from the periumbilical zone, enzymatically digested | ASCs expanded in vitro | Ultrasound-guided intratendinous injection of 6 × 106 ASCs | 12 months VAS knee VISA-P Tegner score MRI |
Khoury et al. 2021b [60] | Prospective longitudinal case series exploratory study (Argentina) | Chronic lateral elbow tendinopathy (MRI) | Lipoaspirated autologous adipose tissue from the periumbilical zone, enzymatically digested | ASCs expanded in vitro | Ultrasound-guided intratendinous injection of 8 × 106 ASCs | 12 months VAS QuickDASH-Compulsory score QuickDASH-Sport score MRI |
Freitag et al. 2020 [61] | Case report (Australia) | Elbow tendinopathy (US) | Lipoaspirated autologous abdominal subcutaneous adipose tissue, enzymatically digested | ASCs | Ultrasound-guided intratendinous injection of 1 × 109 ASCs (1 mL) combined with 1 mL autologous PRP in tendon fibril discontinuity/tearing | 30 months NPRS PRTEE |
3.2. Characteristics of Tendinopathic Patients
3.3. Therapeutic Efficacy and Adverse Reactions to ASCs Intratendinous Injections
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Reference | Tendinopathy and Treatment | n (Baseline) | Age (Years), Sex (%M), BMI (kg/m2) | Inclusion Criteria | Exclusion Criteria | n (Follow-Up) |
---|---|---|---|---|---|---|
Kim et al. 2017 [55] | Rotator cuff disease Intratendinous injection of autologous ASCs during arthroscopic rotator cuff repair | 35 | 59.2, 43%, 26.6 | -full-thickness rotator cuff tear diagnosed by a clinical examination, conventional radiography and MRI -shoulder pain and/or functional limitations despite at least 3 months of nonsurgical treatment (anti-inflammatory medication, physical therapy) |
| 35 |
Jo et al. 2016 [56] | Rotator cuff disease Ultrasound-guided intratendinous injection of autologous ASCs | 20 | 56.7, 8.3%, 23.4 | -19 years of age and older -unilateral shoulder pain of at least 3 months, with failure of conservative treatments -partial-thickness rotator cuff tear confirmed with MRI/US |
| 19 |
Usuelli et al. 2018 [58] | Unilateral or bilateral chronic tendinopathy of Achilles tendon Ultrasound-guided injection of autologous SVF | 21 | 47.3, 67%, - | -unilateral or bilateral chronic tendinopathy of the Achilles tendon recalcitrant to traditional conservative treatments (NSAIDs, eccentric loading exercises, stretching and biophysical therapy) -symptoms lasting for at least 3 months -age between 18 and 55 -VAS pain >5 at the first visit |
| 21 |
Lee et al. 2015 [57] | Chronic lateral epicondylosis Ultrasound-guided intratendinous injection of allogeneic ASCs mixed with fibrin glue | 12 | 24.4, 42%, 51.8 | -lateral elbow pain for at least 6 months -failure of conventional treatments (physical therapy, oral medication, prolotherapy and steroid injection) |
| 12 |
Khoury et al. 2021a [59] | Chronic insertional patellar tendinopathy Ultrasound-guided intratendinous injection of autologous ASCs | 16 | 34.6, 80%, 23.7 | -exercise-related pain located at the patellar tendon insertion for at least 6 months -tenderness to palpation of the tendon substance and thickening and tear of the patellar tendon -failure of exercise-based rehabilitation and different treatment modalities for a minimum of 6 months |
| 14 |
Khoury et al. 2021b [60] | Chronic lateral elbow tendinopathy Ultrasound-guided intratendinous injection of autologous ASCs | 19 | 46.5, 61%, - | -lateral elbow tendinopathy diagnosis -pain and disability for at least 4 months -failure of conventional treatments (eccentric rehabilitation protocol, oral medication, prolotherapy, extracorporeal shock wave therapy, steroid injections, unguided tendon injections with dipropionate and sodium phosphate of betamethasone and PRP) |
| 18 |
Reference | Tendinopathy and Treatment | n (Baseline) | Age (Years), Sex BMI (kg/m2) | Case Presentation | n(Follow-Up) | |
Freitag et al. 2020 [61] | Elbow tendinopathy Ultrasound-guided intratendinous injection of autologous ASCs combined with autologous PRP | 1 | 52, M, - |
| 1 |
Reference | Tendinopathy | Treatment Group (n) | Control Group (n) | Significant Score at Follow-Up (p Value) | Significant Score at Intermediate Time Points (p Value) | Score Changes Confirmed by MRI/US | AE Reported (n of Patients) |
---|---|---|---|---|---|---|---|
Kim et al. 2017 [55] | Rotator cuff disease | Autologous ASCs in fibrin glue (35) | Arthroscopic rotator cuff repair alone (controls) (35) | Rate of tear recurrence Controls: 28.5% ASCs: 14.3% (p < 0.001) | - | MRI | - |
Jo et al. 2018 [56] | Rotator cuff disease | Autologous ASCs (19) 3 low-dose; 3 mid-dose; 13 high-dose | Baseline (19) | SPADI mid baseline: 63.8; 6 months: 12.8 (p < 0.05) high baseline: 75.4; 6 months: 17.7 (p < 0.001) Constant score mid baseline: 60.9; 6 months: 77.1 (p < 0.05) high baseline: 55.7; 6 months: 66.9 (p < 0.05) VAS high baseline: 45.4; 6 months: 25.9 (p < 0.001) | high: reduced vs. baseline at month 1 and 3 (both p < 0.001) high: increased vs. baseline at month 1 (p < 0.001) high: reduced vs. baseline at month 1 and 3 (both p < 0.001) | MRI | low: 1 mid: 1 high: 3 |
Usuelli et al. 2018 [58] | Unilateral or bilateral chronic tendinopathy of Achilles tendon | Autologous SVF containing ASCs (21) autologous PRP (23) | Baseline (21) Baseline (23) | VAS SVF and PRP (6 months): reduced vs. baseline (p < 0.001) AOFAS SVF and PRP (6 months): increased vs. baseline (p < 0.001) VISA-A SVF and PRP (6 months): increased vs. baseline (p < 0.001) | SVF and PRP: reduced vs. baseline at 15 days, month 1–2–4 (all p < 0.001) SVF: reduced vs. PRP at 15 days and 1 month (both p < 0.05) SVF: increased vs. baseline at 15 days, month 1–2–4 (all p < 0.001) PRP: increased at baseline at month 2–4 (both p < 0.001) SVF: increased vs. PRP at 15 days (p < 0.05) SVF and PRP: increased vs. baseline at month 1–2–4 (all p < 0.001) SVF: increased vs. PRP at month 1 (p < 0.05) | - | |
Lee et al. 2015 [57] | Chronic lateral epicondylosis | allogeneic ASCs mixed with fibrin glue (12) 6 low-dose (106) 6 high-dose (107) | baseline (12) | VAS baseline: 66.8; all (13 months): 14.8 (p < 0.0001) MEPI baseline: 64.0; all (13 months): 90.6 (p < 0.001) | all reduced vs. baseline at week 6, month 1 and 2 (all p < 0.01) all increased vs. baseline at week 6, month 1 and 2 (all p < 0.01) | US | - |
Khoury et al. 2021a [59] | Chronic insertional patellar tendinopathy | autologous ASCs (14) | baseline (14) | knee VISA-P baseline: 43.8; 12 months: 78.7 (p < 0.05) VAS baseline: 7.4; 12 months: 1.5 (p < 0.05) Tegner score baseline: 2.3; 12 months: 7.2 (p < 0.05) | increased vs. baseline at month 3 and 6 (both p < 0.05) reduced vs. baseline at month 3 and 6 (both p < 0.05) increased vs. baseline at month 3 and 6 (both p < 0.05) | MRI | 2 |
Khoury et al. 2021b [60] | Chronic lateral elbow tendinopathy | autologous ASCs (18) | baseline (18) | VAS baseline: 6.28; 12 months: 0.74 (p < 0.001) QuickDASH-Compulsory score baseline: 51.38; 12 months: 5.76 (p < 0.001) QuickDASH-Sport score baseline: 56.94; 12 months: 8.68 (p < 0.001) | reduced vs. baseline at month 1 and 6 (both p < 0.001) reduced vs. baseline at month 1 and 6 (both p < 0.001) reduced vs. baseline at month 6 (p < 0.001) | MRI | 2 |
Freitag et al. 2020 [61] | Elbow tendinopathy | autologous ASCs combined with autologous PRP (1) | baseline (1) | NPRS baseline: 9; 30 months: 0 PRTEE baseline: 85; 30 months: 0 | baseline: 9; 30 months: 0 baseline: 85; 30 months: 0 | US | - |
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Itro, A.; Trotta, M.C.; Miranda, R.; Paoletta, M.; De Cicco, A.; Lepre, C.C.; Tarantino, U.; D’Amico, M.; Toro, G.; Schiavone Panni, A. Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review. Pharmaceutics 2022, 14, 1151. https://doi.org/10.3390/pharmaceutics14061151
Itro A, Trotta MC, Miranda R, Paoletta M, De Cicco A, Lepre CC, Tarantino U, D’Amico M, Toro G, Schiavone Panni A. Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review. Pharmaceutics. 2022; 14(6):1151. https://doi.org/10.3390/pharmaceutics14061151
Chicago/Turabian StyleItro, Annalisa, Maria Consiglia Trotta, Roberta Miranda, Marco Paoletta, Annalisa De Cicco, Caterina Claudia Lepre, Umberto Tarantino, Michele D’Amico, Giuseppe Toro, and Alfredo Schiavone Panni. 2022. "Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review" Pharmaceutics 14, no. 6: 1151. https://doi.org/10.3390/pharmaceutics14061151