Clinical application of concentrated bone marrow aspirate in orthopaedics: A systematic review

Table 3 Studies evaluating concentrated bone marrow aspirate in the treatment of osteoarthritis

Ref.	Tissue	BMAC preparation	Concen-tration	Study design/methods/follow up	Outcomes measured	Results	LOE
Centeno et al[20]	Knee	60 mL of BMA from iliac crest was obtained toproduce 1-3 mL of BMAC. 60 cc of heparinized IV venous blood drawn to be used for isolating PRP and platelet lysate. Lipoaspirate - miniliposuction of the posterior superior buttocks or lateral thigh was performed under ultrasound and minimally processed (centrifuged) adipose tissue was injected into the articular space. Preparations were injected into the articular space of the knee together (5-10 cc) between the meniscus on the most painful side and over lying collateral ligament	NS	Data from registry. (1) n = 616 - BMAC+ PRP vs (2) BMAC + PRP + adipose graft. Outcomes and complication questionnaires at 1, 3, 6, 12 mo completed. 2 groups (A-BMAC and PRP protocol, B BMAC and PRP plus adipose fate graft (lipoaspirate)	LEFS, NPS, subjective percentage improvement rating, frequency and type of adverse events	Mean LEFS score increased in both groups and mean NPS decreased in both groups. AE rates were 6% without graft and 8.9% with graft. No difference between groups. Addition of adipose graft did not provide a detectible benefit over BMAC alone	IV
Centeno et al[21]	Knee	10-15 cc whole bone marrow aspirate harvested from 6-8 sites on posterior iliac crest (3-4 each side). Centrifuged and cells isolated. Patient heparinized blood for PRP and PL. Aspirates mixed together and injected into joint. Cell counts were counted four times and average was taken under microscope for total nucleated cell count	Lower and higher cell count groups defined using threshold of 4 × 104 cells	Data from registry. n = 373 patients that received BMAC combined with PRP and PL injections for 424 OA knees	Clinical scales assessed at baseline, 1, 3, 6, 12 and annually thereafter. NPS, LEFS, pain and functional outcome measures	Significant positive results with treatment for all pain and functional metrics. Higher cell group reported lower post treatment numeric pain scale values (P < 0.001). No significant difference detected for other metrics	IV
Haleem et al[22]	Femoral condyle	20 mL BMA from iliac crest isolated with density gradient (Ficoll-Paque), supplemented with 10% fetal bovine serum and penicillin streptomycin. Microfracture performed and sclerotic bone curetted. Autologous periosteal flap harvested from anteromedial ispilateral proximal tibia to fit defect size and stuffed into place. 1 mL platelet concentrate and 1 mL fibrinogen and 1 mL thrombin placed with BMAC PR fibrin glue	NS	n = 5, treated with BMAC + PRF	At 6 and 12 mo: Lysholm and Revised HHS Knee Score, XR and MRI. 2 patients had follow up arthroscopy at 12 mo rated by ICRS	All patients had statistically significant improvement at 6 and 12 mo (P < 0.005). No statistically significant difference between 6 and 12 mo post op in clinical scores. ICRS were near normal for 2 patients who consented to arthroscopy. MRI of 3 patients at 12 mo showed complete defect filling and complete surface congruity with native cartilage. Two patients showed incomplete congruity. BMAC on platelet rich fibrin gel as a scaffold may be effective to promote repair of articular cartilage defects	IV
Koh et al[23]	Knee	60 mL BMA from Iliac crest processed with MarrowStim Concentration Kit (Biomet) to obtain 3-4 mL of BMAC. Adipose tissue harvested from buttocks through liposuction. All fluid removed from knee arthroscopically. Lesion filled with cell suspension and held stationary for 10 minutes with defect facing upwards. Adherence of MSC confirmed. No marrow stimulation procedures were performed	Average of 3.8 × 106 (2.5-6.1 × 106)	n = 37 knees using second-look arthroscopy after mesenchymal stem cell implantation for cartilage lesions done 12 mo post op	IKDC, Tegner, cartilage repair assessed using ICRS grading	IKDC and Tegner sores significantly improved (P < 0.001). ICRS overall repair grades 2/37 were normal, 7/37 were near normal, 20/37 abnormal, 8/37 severely abnormal.). Patient satisfaction: 33/34 reported good to excellent satisfaction. High BMI (> 27.5) and large lesion (> 5.4 cm2) had significant prediction of poor clinical and arthroscopic outcomes (P < 0.05)	IV
Shapiro et al[24]	Knee	52 mL BMA from iliac crest concentrated in Arteriocyte Magellan Autologous Platelet Separator System centrifuge to yield 6 mL of cellular product	NS	n = 25 BMAC, n = 25 saline (patients had bilateral knee pain)	OARSI measure, VAS score, safety outcomes, pain relief, function	OARSI and VAS decreased significantly from baseline at 1wk, 3 mo, 6 mo (P < 0.019), no difference in pain relief	II

BMA: Bone marrow aspirate; MRI: Magnetic resonance imaging; NS: Not significant; OA: Osteoarthritis; BMI: Body mass index; VAS: Visual analogue scale; OARSI: Osteoarthritis Research Society International.