Type of study | Author | Journal | Publication Date | Technique | Sample Size | Age (years) | Staging | Etiology | Processing of MSCs | Number of Cells | Complications | Follow-up | Conclusions |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Level IV (Landmark study) | Hernigou et al. [8] | Clin Orthop Relat Res | 2002 | CD + BMC implantation | A total of 116 patients (189 hips) | 31 (16 to 61) | SteiInberg I: 59; SteiInberg II: 86; SteiInberg III: 12; SteiInberg IV: 32 | Steroid: 31; Alcohol: 56; Idiopathic: 10; SCD: 64; Organ transplantation: 21; Others: 7 | 150-mL bone marrow aspirate to a concentrated myeloid sus- pension of approximately 30 mL of stem cells | The average total number of colony-forming units injected by hip was estimated to be 25 × 103 cells. | No specific complication. | 7 years (5 to 11 years) | Higher risk of failure for patients with corticosteroid treatment and stage III-IV. Correlation between the greater number of progenitor cells and smaller lesions with better outcomes. |
Level I | Pepke et al. [18] | Orthopedic Reviews | 2016 | Control group: CD alone Treatment group: CD + BMC implantation | Control group: 14 hips; Treatment group: 11 hips | Control group: 44.5 ± 3.3; Treatment group: 44.3 ± 3.4 | ARCO II 25 | Chemotherapy: 2; Immunosuppressive therapy: 4 | 12 ml of bone marrow concentrate suspension was concentrated from 200 to 220 mL of marrow havesed from the iliac crest. | 118.9 × 106 cells/ml (a total of 10 ml was injected). | NR | 24 months | No significant benefit from the additional injection of BMC in the short term. |
Level I | Tabatabaee et al. [16] | J Arthroplasty | 2015 | Control group: CD alone Treatment group: CD + concentrated bone marrow aspirates | Control group: 14 hips; Treatment group: 14 hips | Control group: 26.8 ± 5.8; Treatment group: 31 ± 11.4 | ARCO I 5; ARCO II 16; ARCO III 7 | Steroid: 19; Idiopathic: 9 | Bone marrow concentrate suspension concentrated from approximately 200 mL of bone marrow aspirate. | 2 million cells/ml (injected volume was not reported). | No serious complications were noted in either of the clinical groups. | 24 months | BMC injection with CD could be an effective therapy for the early stages of AVN; score improvement. |
Level I | Mao et al. [15] | J Bone Mine Res | 2015 | Control group: Porous tantalum rod implantation; Treatment group: Porous tantalum rod implantation + intra-arterial injection of peripheral blood MSCs | Control group: 41 hips; Treatment group: 48 hips | Control group: 36.12 ± 11.34; Treatment group: 34.60 ± 11.50 | ARCO I 18; ARCO II 52; ARCO III 19 | Steroid: 31; Alcohol: 32; Idiopathic: 26 | Injections of G-CSF for 4 days to mobilize PBSCs, and then, a collection process was performed. | Injected cells: 2.47 × 108 mononuclear cells, which contained 1.71 ± 0.7 × 106 CD34+ cells. | No complication was observed. | 36 months | Combination treatment provides superior results regarding clinical outcomes such as pain, function, activity, and motion compared with biomechanical support alone. |
Level I | Ma et al. [14] | Stem Cell Res Ther | 2014 | Control group: CD + autologous bone graft Treatment group: CD + autologous bone graft with BMC | Control group: 24 hips; Treatment group: 25 hips | Control group: 34.78 ± 11.48; Treatment group: 35.60 ± 8.05 | Ficat I: 7; Ficat II: 32; Ficat III: 10 | Steroid: 26; Alcohol: 7; Idiopathic: 12 | Centrifuged and then loaded into the cylindrical bone. | The average number of bone marrow cells loaded into the cylindrical bone was approximately 3 × 109 nucleated cells. | No complication was observed. | 24 months | Implantation of the autologous BMC graft combined with CD is effective to prevent further AVN. The stage of AVN might affect the outcome, while etiological factors do not. |
Level I | Rastogi et al. [13] | Musculoskelet Surg | 2013 | Control group: CD and unprocessed bone marrow injection Treatment group: CD + isolated mononuclear cells | Control group: 30 hips; Treatment group: 30 hips | Control group: 33.0 ± 7.71; Treatment group:34.67 ± 7.02 | NR | Steroid: 18; Alcohol: 8; Idiopathic: 26; Smoking: 8 | Treatment group: 5 ml of isolated mononuclear cells (The entire procedure took 1 h). Control group: 30–50 ml of unprocessed bone marrow. | Treatment group: 1.1 × 108 cells. Control group: not reported. | No complications were noted in both group. | 24 months | Control and treatment group scores show significant differences when compared with preoperative scores, without statistically significant inter-group differences in clinical scores. |
Level I | Sen et al. [12] | J Arthroplasty | 2012 | Control group: CD alone Treatment group: CD + autologous bone marrow mononuclear cell | Control group: 25 hips; Treatment group: 26 hips | NR | ARCO I, II | Steroid: 14; Alcohol: 6; Idiopathic: 1; Pregnancy: 1; Cushing disease: 1; Trauma: 17 | 2 ml of mononuclear cells was havested from 120 to 180 ml of bone marrow aspirates in appromixmately 2 h. | Injected cells: 5 × 108 mononuclear cell to keep to keep the CD34 + cell count more than 5 × 107 . | No complications were observed. | 24 months | BMC instillation can result in better clinical outcomes and hip survival, with only 1 THR in the treatment group vs 6 in the control group. Better outcomes in traumatic AVN than in non-traumatic AVN. |
Level I | Zhao et al. [11] | Bone | 2012 | Control group: CD alone Treatment group: CD with cultured bone-marrow derived MSCs | Control group: 44 hips; Treatment group: 53 hips | Control group: 33.8 ± 7.7; Treatment group: 32.7 ± 10.5 | ARCO IC 5; ARCO IIA 30; ARCO IIB 46; ARCO IIC 23 | Steroid: 24; Alcohol: 19; Idiopathic: 30; Trauma: 20; Caisson disease: 11 | 10 mL of subtrochanteric bone marrow was aspirated and allowed to proliferate in vitro for two weeks. | Implanted cells: 2 × 106 cells. | No complications were observed. | 60 months | Ex vivo expansion of bone marrow-derived MSCs and implantation provide significant improvements in pain and other joint symptoms and delay or avoid the progression of osteonecrosis and THA. |
Level I | Gangji et al. [10] | Bone | 2011 | Control group: CD alone Treatment group: CD + BMC implantation | Control group: 11 hips; Treatment group: 13 hips | Control group: 45.7 ± 2.8; Treatment group: 42.2 ± 2.6 | ARCO I 4; ARCO II 20 | Steroid: 20; Alcohol: 2; Idiopathic: 2 | Concentrated to a final volume of 49.7 ± 2.3 ml. | Contained 1.9 ± 0.2 × 109 mononuclear cells, including 1.0 ± 0.1% of CD34+ cells. | No complications were observed. | 60 months | BMC implantation in the necrotic lesion provides better results in early osteronecrosis and delays its progression. Reduced pain and decreased volume of the necrotic lesion. |
Level II | Houdek et al. [23] | Clin Orthop Relat Res | 2018 | A consecutive cohort, CD + BMC + PRP | A total of 22 patients (35 hips) | 43 (22 to 66) | Pennsylvania Stage 1 or Stage 2 | Steroid | 60 to 120 cc of bone marrow was concentrated to 6 to12 cc of BMC | 2.5 × 106 to 6.8 × 107 cells. | NR | 3 years (2 to 4 years) | Successful results were seen when the nucleated cell count was high and the modified Kerboul grade was low. |
Level II | Pilge et al. [49] | Ortho Rev. | 2016 | Control group: CD + iloprost iv. Treatment group: CD + iloprost iv. + BMC implantation | Control group: 10 hips; Treatment group: 10 hips | 38.35 (15 to 58) | ARCO II: 12; ARCO III: 6; ARCO IV: 2 | Steroid: 5; Chemotherapy: 6; Idiopathic: 8; Smoke: 1 | 60 ml of bone marrow aspirate was concentrated. | Between 7 and 10 mL. | No serious adverse reaction to iloprost infusion. Patients had flush symptoms and 2 patients complained of a mild headache during infusion. | 30.6 (4–69) months | An improvement in clinical scores was shown in the treatment group but not in the control group. |
Level II | Gangji et al. [17] | J Bone Joint Surg Am | 2004 | Control group: CD alone Treatment group: CD + BMC implantation | Control group: 8 hips; Treatment group: 10 hips | Control group: 48.8 ± 11.2; Treatment group: 40.9 ± 9.8 | ARCO I: 2; ARCO II: 16 | Steroid: 14; Alcohol: 2; Idiopathic: 2 | Approximately 400 mL of marrow was obtained from the anterior iliac crest and concentrated to a mean final volume of 51 ± 1.8 mL. | 2.0 ± 0.3×  109, including 1.0% ± 0.2% CD34+ cells. | No major side effects was observed. Two patients complained of pain at the site of the bone-marrow aspiration; coagulase- negative staphylococc was cultured form the bone marrow in one patient; A hematoma was observed at the site of the CD in another patient | 24 months | CD + BMC provides significant decreases in the level of pain and other joint symptoms. The volume of necrotic lesions significantly improved only in the treatment group. |