Introduction
Material and methods
Results
Preclinical studies
Author and year | Animal and OA model | Joint | Treatment | Harvest site | BMAC characteristics | Follow-up and evaluation | Results |
---|---|---|---|---|---|---|---|
Desando G et al. 2018 [27] | Rabbit (48 knees) OA induced by ACL transection | Knee | 12 BMAC vs. 12 cultured BMSCs vs. 12 BMAC + HA vs. 12 cultured BMMCs + HA Single IA injection | Iliac crest | Centrifugation procedure at 400g for 10 min at 20 °C 2 × 106 cells/ml | 8 weeks Cell biodistribution, histologic, immunohistochemical, and synovial fluid analysis | BMAC showed effectiveness for the injective OA treatment, with similar results than BMSCs and better results for the association of BMAC + HA. |
Wang Z et al. 2018 [28] | Goat (24 knees) OA induced by ACL transection and meniscectomy | Knee | 6 BMAC vs. 6 saline vs. 6 PRP Three IA injections (once every 4 weeks) | Iliac crest | Two-step centrifugation procedure 5 ml with 1190.3 × 106 cells/ml | 6 weeks Macroscopic, histologic, immunohistochemical, and synovial fluid analysis | Higher cartilage protection in the BMAC group than both PRP and saline groups. |
Song F et al. 2014 [29] | Sheep (18 knees) OA induced by ACL transection and meniscectomy | Knee | 6 BMSCs vs. 6 saline vs. 6 cultured MSCs Single IA injection | Iliac crest | BMSCs were isolated by density gradient centrifugation, and were resuspended in PBS 5 ml with 0.9 × 106 cells/ml | 8 weeks Macroscopic, histopathologic, ELISA and proteoglycan assay, RT-PCR analysis of cartilage | BMSCs and cultured MSCs provided both good results in terms of macroscopic and histologic findings, GAG protection, cytokines, and cartilage biomarkers changes. |
Singh A et al. 2014 [30] | Rabbit (20 knees) OA induced by ACL transection | Knee | 10 BMSCs vs. 10 saline Single IA injection | Proximal tibia | BMSCs were isolated by density gradient following Pittenger’s method 1 ml with 1 × 106 cells/ml | 20 weeks Macroscopic, radiologic, and histopathologic analysis | BMSCs provided significant histopathological and radiological improvement compared with control group. |
Clinical studies
Author and year | Study design | Joint | Treatment | Harvest site | Bone marrow concentration and injected amount | Patient, n (M/F) Age, mean (SD or range) | F-up | Results and adverse events | mCMS |
---|---|---|---|---|---|---|---|---|---|
Anz AW et al. 2020 [31] | Unblinded RCT | Knee | BMAC vs. LR-PRP Single IA injection | PSIS | Dual-Spin protocol/disposable PureBMc - EmCyte (Fort Myers, FL, USA) 7 ml of BMAC | BMAC group 45 (27/18) 56 years (11) LR-PRP group 41 (22/19) 52 years (12) | 12 m | All scores for both PRP and BMAC groups significantly improved up to 12 months, with no difference between PRP and BMAC at any time point. No adverse events were reported. | 60 |
Mautner K et al. 2019 [32] | Retrospective comparative study | Knee | BMAC vs. MFAT Single IA injection | PSIS | EmCyte centrifuge (Fort Myers, FL, USA) 8 ml of BMAC | BMAC group 41 (24/17) 59 years (1) MFAT group 35 (12/23) 63 years (11) | 22 m | There were significant improvements in pain and function with both treatments, without a significant difference between the two groups. No adverse events were reported. | 35 |
Shapiro SA et al. 2019 [33] | Blinded RCT (self-controlled) | Knee (bilateral) | BMAC vs. saline Single IA injection | PSIS | Magellan Autologous Platelet Separator System (Arteriocyte, USA) 5 ml of BMAC + 10 ml of PPP BMAC product contained a median of 56% MNCs (150 × 106 WBC, 80 × 106MNC, 4.4 × 106 hematopoietic stem cells, and 34,000 MSCs) | Bilateral OA patients 25 (7/18) 60 years (42–68) | 12 m | No difference between BMAC- and saline-treated knees in patients with bilateral knee OA. No adverse events were encountered. | 57 |
Subasi T et al. 2019 [34] | Prospective case series | Knee | BMAC Single IA injection (followed 1 month later by a PRP injection) | PSIS | MC kitTM (nFinders, Seoul, Korea) 4 ml of BMAC | 3 (0/3) 58 years (10) | 2 m | IA BMAC and PRP treatments may have positive effects on pain, functional status, and quality of life in patients with knee OA. No side effects or tractable pain were detected. | 27 |
Centeno C et al. 2018 [35] | Unblinded RCT | Knee | BMAC + platelet products vs. exercise therapy (pre-injection of dextrose, post-injection of PRP, hydrocortisone, and doxycycline after 2–4 days) Single IA injection | PSIS | The aspirate was processed in a sterile ISO-7 class clean room 5–7 ml injectate solution (75% of BMAC) | BMAC group 26 54 years (9) Exercise group 22 57 years (8) | 24 m | The use of BMAC with platelet products yielded better results than exercise therapy. No serious adverse events were identified. One patient reported a persistent popliteal fossa fluid accumulation, which was aspirated. | 55 |
Hernigou P et al. 2018 [36] | Unblinded RCT | Knee | BMAC vs. TKA Single subchondral injection | ASIS | 40 ml of BMAC in the subchondral medial and lateral femorotibial compartments. BMAC contains an average of 6500 MSCs/ml | 30 (12/18) 28 years (18–41) | 144 m | Subchondral BMAC was an effective procedure for treating young patients with knee OA following secondary osteonecrosis. During the postoperative period, the number of adverse events was higher in the TKA group. | 67 |
Shaw B et al. 2018 [37] | Retrospective case series | Knee | BMAC 4 IA injections (1 every 2 weeks) | PSIS | The BMAC was spun in a centrifuge, and the upper portion without visible red cells was isolated from the centrifuged BMAC. 5 ml of BMAC + 1 ml of ropivacaine | 15 (5/10) 68 years (8) | 3 m | Outcomes at the final follow-up after the fourth treatment were statistically significant compared with outcomes at baseline. No serious adverse events were reported. | 24 |
Themistocleous GS et al. 2018 [38] | Retrospective case series | Knee | BMAC Single IA injection | ASIS | Single-spin centrifugation technique (Hettich® Rotofix 32A centrifuge) 10 ml of BMAC | 121 (35/86) 70 years (50–85) | 11 m | BMAC was a safe and reliable procedure that resulted in clinical improvement in patients with grades 3 and 4 knee OA. There were no adverse events or complications. | 41 |
Centeno C et al. 2015 [39] | Retrospective comparative study | Knee | BMAC (higher cell count) + platelet products vs. BMAC (lower cell count) + platelet products Single IA injection | PSIS | The aspirate was processed in a sterile ISO-7 class clean room. Higher cell count group BMAC: > 4 × 108 cells Lower cell count group BMAC: ≤ 4 × 108 cells | Higher cell count 224 54 years (13) Lower cell count 185 50 years (16) | 12 m | Patients receiving a higher concentration of cells reported a better pain outcome in comparison with the lower dose group. No adverse events were reported. | 28 |
Centeno C et al. 2014 [43] | Retrospective comparative study | Knee | BMAC + platelet products vs. BMAC + platelet products + adipose graft (pre-injection of dextrose) Single IA injection | PSIS | The aspirate was processed in a sterile ISO-7 class clean room. 1–3 ml BMAC injected intra-articularly and in painful or damaged structures | Group A 518 54 years (14) Group B 163 60 years (10) | 12 m | Although improvements were statistically significant, the differences between the groups were not. No adverse events secondary to the procedure were reported. | 23 |
Kim JD et al. 2014 [41] | Prospective case series | Knee | BMAC + adipose tissue Associated surgery in 16% of patients Single IA injection | ASIS or PSIS | SmartPReP2 BMAC2 kits (Harvest Technology, USA) 7 ml BMAC + 10 ml ADSCs | 41 (17/24) 61 years (53–80) | 12 m | BMAC injection significantly improved both knee pain and function in the patients with knee OA. No adverse events were reported. | 44 |
Darrow M et al. 2018 [42] | Retrospective case series | Hip | BMAC 4 intra-articular injections (1 every 2 weeks) | PSIS | The BMAC was spun in a centrifuge, and the upper portion without visible red cells was isolated from the centrifuged BMAC. 5 ml of BMAC + 1 ml of ropivacaine | 4 (3/1) 67 years (10) | 4 m | All patients experienced decreased pain and improved functionality compared with baseline. No adverse events were reported. | 23 |
Centeno C et al. 2014 [43] | Retrospective case series | Hip | BMAC + platelet products (pre-injection of dextrose) Single IA injection | PSIS | The aspirate was processed in a sterile ISO-7 class clean room. 1–4 ml of BMAC + 2 ml of PRP + PL | 216 (124/92) 57 years (11) | 9 m | BMAC injections for hip OA demonstrated encouraging results for improved outcomes with no significant complications. There were no severe or serious adverse events. | 26 |
Darrow M et al. 2019 [44] | Retrospective comparative study | Shoulder | BMAC vs. WBM 1 or 2 IA injections | PSIS | The BMAC was spun in a centrifuge, and the upper portion without visible red cells was isolated from the centrifuged BMAC. 5 ml of BMAC + 1 ml of ropivacaine | 32 | 8 m | Injective BMAC or WBM treatment in patients with shoulder OA significantly improved resting pain, active pain, and functionality score, with greater results in group with 2 injections. No adverse events were reported. | 24 |
Centeno C et al. 2015 [45] | Retrospective case series | Shoulder | BMAC + platelet products (pre-injection of dextrose) Single IA injection | PSIS | The aspirate was processed in a sterile ISO-7 class clean room. 1–4 ml of BMAC + 1 ml of PRP + 1 ml of PLCell count: 3.85 × 108 | 34 (27/7) 52 years (17) | 11 m | The use of BMAC to treat shoulder OA was effective at improving pain and function. No serious adverse events were reported. | 29 |
Rodriguez-Fontan F et al. 2018 [46] | Prospective case series | Knee Hip | BMAC Single IA injection | ASIS | BioCUE Platelet Concentration System (Zimmer Biomet, Warsaw) 12 ml of BMAC | 19 (3/16) 58 years (13) | 24 m | IA injections of BMAC for the treatment of early knee or hip OA were safe and demonstrated satisfactory results in 63.2% of patients. No serious adverse events were reported. | 42 |
Centeno C et al. 2016 [47] | Retrospective comparative study | Knee Hip Ankle Shoulder | (A) BMAC + platelet products vs. (B) BMAC + platelet products + adipose graft vs. (C) cultured MSCs (pre-injection of dextrose) Single IA injection | PSIS | The aspirate was processed in a sterile ISO-7 class clean room 1–3 ml of BMAC containing 0.2–1.5 × 108 nucleated cells | A: 246 (134/113) 60 years (11) B: 1589 (964/626) 56 years (14) C: 535 (343/192) 53 years (13) | 26 m | Adverse events were reported in 12.1% of the study population. Lowest rate of adverse events was among those patients receiving BMAC injections alone, compared with patients that received also adipose graft. | 24 |
Sampson S et al. 2016 [48] | Retrospective case series | Knee Ankle Hip Shoulder | BMAC Single IA injection PRP injection after 8 weeks | PSIS | Thermo Scientific CL2 centrifuge (MA, USA) Larger joints: 5 ml of BMAC Smaller joints: 1–2 ml of BMAC | 125 57 years (23–79) | 5 m | IA injection of BMAC, followed by a PRP injection, provided short-term benefits in OA. No adverse events were reported. | 29 |