Bone Marrow Aspirate Concentrate versus Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Combined Cartilage Regeneration Procedure in Patients Undergoing High Tibial Osteotomy: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Meta-Analyses Principles
2.2. Search Strategy
2.3. Study Criteria and Screening Process
2.4. Data Extraction and Quality Control
2.5. Statistical Analyses
3. Results
3.1. Study Characteristics
3.2. Methodological Quality
Study | Level of Evidence | Design | Type of Osteotomy | Intervention | Gender (M, F) | Age (Years) | BMI (kg/m2) | Number of Patients in Intervention Group |
---|---|---|---|---|---|---|---|---|
Cavallo, 2018 [35] | IV | retrospective case series study | HTO (medial opening-wedge) | bone marrow-derived cells + PRF | BMAC (15, 9) | 47.9 ± 12.3 | Not reported | 24 |
Song, 2020 [36] | IV | retrospective case series study | HTO | hUCB-MSC + multiple holes | hUCB-MSC (2, 23) | 64.9 ± 4.4 | 24.9 ± 3.1 | 25 |
Song, 2020 [37] | IV | retrospective case series study | HTO (uniplanar osteotomy) | hUCB-MSC + multiple holes | hUCB-MSC (30, 95) | 58.3 ± 6.8 | 25.6 ± 2.7 | 125 |
Jin, 2021 [34] | III | retrospective comparative study | HTO (biplanar opening wedge osteotomy) | BMAC + MFx vs. MFx | BMAC (11, 37) | 56.9 ± 6.1 | 25.8 ± 3.1 (range, 18.1–33.2) | 48 |
Chung, 2021 [38] | IV | retrospective case series study | HTO (biplanar opening wedge osteotomy) | hUCB-MSC + multiple drill holes | Not reported | 56.6 (range, 43–65) | 25.8 (range, 20.9–33.2) | 93 |
Lee, 2021 [24] | III | retrospective comparative study | HTO (biplanar opening wedge osteotomy) | BMAC + MFx vs. hUCB-MSC + MFx | BMAC (6, 36); hUCB-MSC (6, 26) | BMAC, 60.7 ± 4.1; hUCB-MSC, 58.1 ± 3.6 | BMAC, 26.1 ± 2.8; hUCB-MSC, 26.6 ± 3 | BMAC (42), hUCB-MSC (32) |
Yang, 2022 [23] | III | retrospective cohort study | HTO (biplanar opening wedge osteotomy) | BMAC + MFx vs. hUCB-MSC + MFx | BMAC (17, 38); hUCB-MSC (13, 42) | BMAC, 55.0 ± 7.3; hUCB-MSC, 56.4 ± 5.3 | BMAC, 27.2 ± 3.9 hUCB-MSC, 26.8 ± 3.2 | BMAC (55), hUCB-MSC (55) |
Study | Pre-OP K-L Grade | Pre-OP ICRS Grade | Defect Size (MFC, cm2) | Mean Follow-Up (Months) | HKA Angle (Pre-OP vs. Post-OP) | Clinical Assessment | Number of Patients Undergoing 2nd-Look Arthroscopy | Post-OP ICRS-CRA Grade | Post-OP Koshino Staging |
---|---|---|---|---|---|---|---|---|---|
Cavallo, 2018 [35] | IV or less | Not reported | Not reported | 44.4 ± 17.7 | Pre-OP, varus 1–15°; Post-OP, Not reported | IKDC, KOOS, VAS, Tegner | NA | Not reported | Not reported |
Song,2020 [36] | Not reported | Not reported | 7.2 ± 1.9 | 26.7 ± 1.8 | Pre-OP, ≥3°; Post-OP, Not reported | IKDC, VAS, WOMAC | 14 | I (6), II (8), III (0), IV (0) | Not reported |
Song, 2020 [37] | III or less | IV (125) | 6.9 ± 2.0 | Not reported | Pre-OP, 7.6 ± 2.4; Post-OP, Not reported | IKDC, WOMAC, VAS | 125 | I (73), II (37), III (15), IV (0) | Not reported |
Jin, 2021 [34] | III (36), IV (12) | III (41), IV (7) | 2.3 ± 0.9 | 33.6 ± 6.6 | 7.5 ± 3.4 vs. −2.9 ± 2.5 | IKDC, WOMAC, KSS-pain, KSS-function | 33 | I (1), II (18), III (11), IV (3) | A (2), B (15), C (16) |
Chung, 2021 [38] | III | III or IV | 6.5 (range, 2.0–12.8) | 20.4 (range, 12–42) | Pre-OP, >3°; Post-OP, Not reported | IKDC, WOMAC, KSS-pain, KSS-function, HSS | 49 | I (4), II (34), III (11), IV (0) | A (0), B (12), C (37) |
Lee, 2021 [24] | Not reported | BMAC, MFC 3.9 ± 0.3, MTC 3.9 ± 0.3; hUCB-MSC, MFC 3.9 ± 0.3, MTC 3.9 ± 0.3 | BMAC, 6.5 ± 2.9; hUCB-MSC, 7 ± 1.9 | BMAC, 20.7 ± 6.1; hUCB-MSC, 15.6 ± 2.8 | BMAC, 8.6 ± 3.1 vs. −2.8 ± 3.2; hUCB-MSC, 7.4 ± 2.6 vs. −2.9 ± 1.6 | HSS, WOMAC, KSS-pain, KSS-function | BMAC (42), hUCB-MSC (32) | BMAC (42), I (1), II (18), III (12), IV (11); hUCB-MSC (32), I (6), II (20), III (6), IV (0) | Not reported |
Yang, 2022 [23] | III | BMAC (55), III (5), IV (50); hUCB-MSC (55), III (3), IV (52) | BMAC, 6.4 ± 3.1; hUCB-MSC, 6.2 ± 2.4 | BMAC, 34.2 ± 8.4; hUCB-MSC, 31.0 ± 6.0 | BMAC, 7.6 ± 2.9 vs. −1.5 ± 2.3; hUCB-MSC, 7.5 ± 2.7 vs. −1.6 ± 2.2 | IKDC, KOOS, SF-36, Tegner | BMAC (37), hUCB-MSC (44) | BMAC (37), I (1), II (20), III (11), IV (5); hUCB-MSC (44), I (4), II (30), III (10), IV (0) | BMAC (37), A (4), B (12), C (21); hUCB-MSC (44), A (0), B (12), C (32) |
Study | Pre-OP BMAC or hUCB-MSC Preservation | Rehabilitation | Complication | Number of Patients in Control Group |
---|---|---|---|---|
Cavallo, 2018 [35] | 60 mL of bone marrow from the posterior iliac crest, 15 min centrifugation cycles, a collagen scaffold | Partial weight-bearing was after six weeks; full weight-bearing at eight weeks after evaluation of bone consolidation | Knee swelling due to hemarthrosis in three cases; two cases of infrapatellar nerve injury; one case of delayed union of the osteotomy | NA |
Song, 2020 [36] | hUCB-MSCs were used as a stem cell drug (CARTISTEM, MEDIPost-OP), mixed with sodium hyaluronate, therapeutic dosage 500 μL/cm2 of the defect area with a cell concentration of 0.5 × 107 cells/mL | Non-weight-bearing for eight weeks, full weight-bearing after twelve weeks | Not reported | NA |
Song, 2020 [37] | CARTISTEM® (MediPost-OP, Seongnam-si, Gyeonggi-do, Republic of Korea), 1.5 mL hUCB-MSCs (7.5 × 106 cells/vial) and 4% hyaluronic acid (HA) hydrogel, therapeutic dose 500 mL/cm2 | Partial weight-bearing after four weeks; full weight-bearing at six weeks | Not reported | NA |
Jin, 2021 [34] | contralateral anterior superior iliac spine, at least 40 mL of bone marrow, centrifuged for 4 min at 2500 rpm | Non-weight-bearing to partial weight-bearing after six weeks; full weight-bearing after twelve weeks considering bone healing | Not reported | MFx (43) |
Chung, 2021 [38] | Cartistem, 1.5 mL of cord blood-derived MSCs (7.5 × 106) and 4% HA, 500 mL/cm2 of defect with a cell concentration of 0.5 × 107 cells/mL | Non-weight-bearing to partial weight-bearing walking after six weeks; full weight-bearing after twelve weeks based on the level of bone healing | Some patients, knee swelling for up to one month | NA |
Lee, 2021 [24] | BMAC, contralateral anterior superior iliac spine, at least 40 mL of bone marrow, centrifuge for 4 min at 2500 rpm; Cartistem, hUCB-MSCs-HA hydrogel composites | Non-weight-bearing to partial weight-bearing after six weeks; full weight-bearing after twelve weeks depending on the level of bone healing | Not reported | NA |
Yang, 2022 [23] | BMAC, contralateral anterior superior iliac spine, at least 40 mL of bone marrow, centrifuged for 4 min at 2500 rpm; Cartistem, 1.5 mL of cord blood-derived MSCs (7.5 × 106) and 4% HA, 500 mL/cm2 of defect with a cell concentration of 0.5 × 107 cells/mL | Partial weight-bearing after six weeks; full weight-bearing after twelve weeks. | BMAC: one patient complained of postoperative stiffness | NA |
3.3. Meta-Analysis Results
3.3.1. Clinical Outcomes
- IKDC: In six [23,34,35,36,37,38] of the seven studies, the IKDC score used to evaluate the clinical effects of BMAC or hUCB-MSCs with HTO in patients with varus knee OA was reported. The IKDC subgroup consisted of 127 patients treated using BMAC, and 298 patients treated using hUCB-MSCs. Significant heterogeneity was found (p < 0.001, I2 = 94%), and the random effects model was used. Patients treated with BMAC had significantly improved IKDC scores (SMD, 4.13; 95% CI, 1.23–7.00), as did those in the hUCB-MSC group (SMD, 3.92; 95% CI, 3.65–4.20). However, based on IKDC score, the clinical effects of BMAC vs. hUCB-MSCs for combined cartilage regeneration in patients undergoing HTO were equivalent (p = 0.91; Figure 2).
- WOMAC: In 5 studies [24,34,36,37,38], the WOMAC score was reported, and 90 and 275 participants were included in the BMAC and hUCB-MSC groups, respectively. Since only one [38] of five studies reported WOMAC subscales, while the other four reported only a total WOMAC score, and only the total WOMAC score was compared. Significant heterogeneity was found (p < 0.001; I2 = 93%), and a random effects model was used. Based on the WOMAC index, both BMAC and hUCB-MSCs had a significant clinical effect compared with the preoperative status (SMD 2.09, 95% CI, 1.25–2.93 for BMAC and 3.39, 95% CI, 2.39–4.397 for hUCB-MSCs). However, the difference between groups did not reach statistical significance (p = 0.05; Figure 3).
- Other reported clinical outcomes: Other reported outcomes were KSS score (three studies), VAS (three studies), KOOS (two studies), HSS (two studies), SF-36 (one study), and Tegner activity score (two studies). The mean preoperative and postoperative values for the outcome scales are shown in Table 4. KSS was the only measure used in more than one study to evaluate BMAC and hUCB-MSCs; it was used in three studies [24,34,38]. Mean KSS subscale (pain and function) values were reported in all studies; statistically significant heterogeneity was detected (KSS pain, p = 0.01, I2 = 73%; KSS function, p < 0.001, I2 = 84%). In a random effects model, patients treated with BMAC or hUCB-MSCs showed improved clinical outcome after surgery (KSS pain SMD, 1.51, 95% CI, 0.43–2.59 for BMAC and 1.40; 95% CI, 1.12–1.68 for hUCB-MSCs; KSS function SMD, 1.99, 95% CI, 0.63–3.34 for BMAC and 1.35; 95% CI, 1.08–1.63 for hUCB-MSCs). However, differences in KSS pain and function scores were not found between the two treatment groups (p = 0.85 and p = 0.37, respectively; Figure 4).
3.3.2. Second-Look Arthroscopic Findings
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | Reported Outcomes | IKDC | WOMAC | KSS-Pain | KSS-Function | KOOS | VAS | HSS | SF-36 | Tegner |
---|---|---|---|---|---|---|---|---|---|---|
Cavallo, 2018 [35] | IKDC, KOOS, VAS, Tegner | BMAC, 32.7 ± 15.8 vs. 64.6 ± 21.8 | - | - | - | BMAC, 30.46 ± 11.67 vs. 72.38 ± 20.1 | BMAC, 7.50 ± 1.24 vs. 3.00 ± 2.08 | - | - | BMAC, 1.21 ± 1.02 vs. 2.12 ± 1.39 |
Song, 2020 [36] | IKDC, VAS, WOMAC | hUCB-MSC, 24.3 ± 11.1 vs. 68.5 ± 12.7 | hUCB-MSC, 57.3 ± 11.4 vs. 10.2 ± 7.9 | - | - | - | hUCB-MSC, 76.4 ± 16.6 vs. 12.8 ± 11.7 | - | - | - |
Song, 2020 [37] | IKDC, WOMAC, VAS | hUCB-MSC, 29 ± 7.4 vs. 63.7 ± 10.5 | hUCB-MSC, 43.8 ± 10.7 vs. 8.3 ± 6.2 | - | - | - | hUCB-MSC, 7.6 ± 1.36 vs. 1.7 ± 1.4 | - | - | - |
Jin, 2021 [34] | IKDC, WOMAC, KSS-pain, KSS-function | BMAC, 35.3 ± 12.6 vs. 71.3 ± 11.2 | BMAC, 46.9 ± 13.9 vs. 16.3 ± 9.8 | BMAC, 27.2 ± 7.6 vs. 42.6 ± 7.2 | BMAC, 58.9 ± 13.3 vs. 91.0 ± 10.2 | - | - | - | - | - |
Chung, 2021 [38] | IKDC, WOMAC, KSS-pain, KSS-function, HSS | hUCB-MSC, 39.0 ± 10.4 vs. 71.3 ± 5.9 | hUCB-MSC, 44.5 ± 15.1 vs. 11.0 ± 3.7 | hUCB-MSC, 29.8 ± 11.8 vs. 43.2 ± 5.0 | hUCB-MSC, 61.0 ± 16.3 vs. 81.2 ± 13.7 | - | - | hUCB-MSC, 61.6 ± 12.9 vs. 82.7 ± 13.5 | - | - |
Lee, 2021 [24] | HSS, WOMAC, KSS-pain, KSS-function | - | BMAC, 43.9 ± 12.7 vs. 23.4 ± 11.6; hUCB-MSC, 45.2 ± 8.8 vs. 19.5 ± 15.8 | BMAC, 30.8 ± 11.0 vs. 40.6 ± 6.1; hUCB-MSC, 31.6 ± 10.4 vs. 42.8 ± 7.9 | BMAC, 62.3 ± 11.9 vs. 80.1 ± 15.0; hUCB-MSC, 63.1 ± 11.2 vs. 82.4 ± 15.5 | - | - | BMAC, 57.9 ± 12.9 vs. 79.2 ± 11.5; hUCB-MSC, 56.1 ± 10.6 vs. 84.6 ± 15.5 | - | - |
Yang, 2022 [23] | IKDC, KOOS, SF-36, Tegner | BMAC, 43.9 ± 12.7 vs. 23.4 ± 11.6; hUCB-MSC, 45.2 ± 8.8 vs. 19.5 ± 15.8 | - | - | - | BMAC, 37.7 ± 2.7 vs. 78.2 ± 7.9; hUCB-MSC, 36.8 ± 7.1 vs. 78.4 ± 8.6 | - | - | BMAC, 43.6 ± 10.4 vs. 64.0 ± 11.6; hUCB-MSC, 45.8 ± 12.3 vs. 64.5 ± 11.9 | BMAC, 2.3 ± 0.9 vs. 4.0 ± 0.5; hUCB-MSC, 2.2 ± 0.8 vs. 4.1 ± 0.5 |
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Park, D.; Choi, Y.H.; Kang, S.H.; Koh, H.S.; In, Y. Bone Marrow Aspirate Concentrate versus Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Combined Cartilage Regeneration Procedure in Patients Undergoing High Tibial Osteotomy: A Systematic Review and Meta-Analysis. Medicina 2023, 59, 634. https://doi.org/10.3390/medicina59030634
Park D, Choi YH, Kang SH, Koh HS, In Y. Bone Marrow Aspirate Concentrate versus Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Combined Cartilage Regeneration Procedure in Patients Undergoing High Tibial Osteotomy: A Systematic Review and Meta-Analysis. Medicina. 2023; 59(3):634. https://doi.org/10.3390/medicina59030634
Chicago/Turabian StylePark, Dojoon, Youn Ho Choi, Se Hyun Kang, Hae Seok Koh, and Yong In. 2023. "Bone Marrow Aspirate Concentrate versus Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Combined Cartilage Regeneration Procedure in Patients Undergoing High Tibial Osteotomy: A Systematic Review and Meta-Analysis" Medicina 59, no. 3: 634. https://doi.org/10.3390/medicina59030634