Mid-term results of concentrated autologous bone marrow aspirate transplantation for corticosteroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus

Tomaru, Yohei; Yoshioka, Tomokazu; Sugaya, Hisashi; Shimizu, Yoshiki; Aoto, Katsuya; Wada, Hiroshi; Akaogi, Hiroshi; Yamazaki, Masashi; Mishima, Hajime

doi:10.1007/s00264-018-3959-y

Cited by 16 publications

(17 citation statements)

References 25 publications

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“…Several previous studies [12,13,21,35] focused on cell therapies have found that there was a clinical improvement of symptoms on patients with ONFH including pain and function scores. However, the efficacy of stem cells in the long term is not clear and remains controversial especially on the progression events [9,11,12,36,37].…”

Section: Discussionmentioning

confidence: 97%

Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

et al. 2020

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Background Osteonecrosis of femoral head (ONFH) is a seriously degenerative disease with no effective therapies to slow its progression. Several studies have reported short-term efficacy of stem cells on early-stage ONFH. However, its long-term effect was still unclear especially on progression events. This study was performed to evaluate the long-term efficacy and safety of stem cells and analyze its optimal age group and cell number. Methods Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42020136094. Following PRISMA guideline, we searched 8 electronic databases on January 5, 2020, and rigorous random controlled trials (RCTs) utilizing stem cell therapy on early-stage ONFH were included. Quality and bias were analyzed. Pooled analysis was performed to assess difference between various outcomes. Results A total of 13 RCTs (619 patients with 855 hips) were included. The application of stem cells significantly delayed collapse of femoral head(I2, 70%; RR, 0.54; 95% CI, 0.33 to 0.89; P < .00001) and total hip replacement (THR) (I2, 68%; RR, 0.55; 95% CI, 0.34 to 0.90; P = .02) in the long term. It effectively decreased the events of collapse of femoral head (≥ 60 months) (I2, 0%; RR, 0.37; 95% CI, 0.28 to 0.49; P < .00001) and THR (> 36 months) (I2, 0%; RR, 0.32; 95% CI, 0.23 to 0.44; P < .00001). There existed a beneficial effect for patients under 40 (Collapse of femoral head: I2, 56%; RR, 0.41; 95% CI, 0.23 to 0.76; P = .004) (THR: I2, 0%; RR, 0.31; 95% CI, 0.23 to 0.42; P < .00001). In addition, quantity of stem cells at 108 magnitude had better effects on disease progression events (I2, 0%; RR, 0.34; 95%CI, 0.16 to 0.74; P = .007). Besides, there were no significant differences on adverse events between the stem cell group and control group (I2, 0%; RR, 0.82; 95% CI, 0.39 to 1.73; P = .60). Conclusion Our findings build solid evidence that stem cell therapy could be expected to have a long-term effect on preventing early-stage ONFH patients from progression events, such as collapse of femoral head and total hip replacement. Furthermore, patients under 40 may be an ideal age group and the optimal cell number could be at 108 magnitude for this therapy. Further studies including strict RCTs are required to evaluate a clear effect of stem cells on ideal patient profile and the procedures of implantation.

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Section: Discussionmentioning

confidence: 97%

Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

et al. 2020

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“…To date, BMSC transplantation has been widely applied to treat orthopedic diseases, including SONFH, but satisfactory efficacy has not always been achieved by stem cell transplantation alone [9,10]. Several studies have suggested that specifically-modified BMSCs exerted more powerful effects in SONFH.…”

Section: Introductionmentioning

confidence: 99%

Silencing MicroRNA-137-3p, which Targets RUNX2 and CXCL12 Prevents Steroid-induced Osteonecrosis of the Femoral Head by Facilitating Osteogenesis and Angiogenesis

Kong¹,

Zuo²,

Wang³

et al. 2020

Int. J. Biol. Sci.

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The main pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH) includes decreased osteogenic capacity of bone marrow-derived mesenchymal stem cells (BMSCs) and damaged blood supply to the femoral head. MicroRNAs (miRNAs) have been shown to play prominent roles in SONFH development. However, there is no report that a specific miRNA targeting two genes in two different pathogenic pathways has been applied to this disease. The present study investigated the effects of transplantation of miR-137-3p-silenced BMSCs on the prevention and early treatment of SONFH. First, western blotting and dual luciferase assays were employed to verify that miR-137-3p directly targets Runx2 and CXCL12. Then, silencing of miR-137-3p was found to facilitate osteogenic differentiation of BMSCs, which was confirmed by alkaline phosphatase (ALP) staining, alizarin red staining and qRT-PCR. Silencing of miR-137-3p also promoted angiogenesis by human umbilical vein endothelial cells (HUVECs) in the presence or absence of glucocorticoids. Thereafter, overexpression of Runx2 and CXCL12 without the 3′ untranslated region (3′UTR) partially rescued the effects of miR-137-3p on osteogenesis and angiogenesis, respectively. This finding further supported the hypothesis that miR-137-3p exerts its functions partly by regulating the genes, Runx2 and CXCL12. We also demonstrated that SONFH was partially prevented by transplantation of miR-137-3p-silenced BMSCs into a rat model. Micro-CT and histology showed that the transplantation of miR-137-3p-silenced BMSCs significantly improved bone regeneration. Additionally, the results of enzyme-linked immunosorbent assays (ELISA) and flow cytometry suggested that stromal cell-derived factor-1α (SDF-1α) and endothelial progenitor cells (EPCs) participated in the process of vascular repair. Taken together, these findings show that silencing of miR-137-3p directly targets the genes, Runx2 and CXCL12, which can play critical roles in SONFH repair by facilitating osteogenic differentiation and mobilizing EPCs.Key words: steroid-induced osteonecrosis of the femoral head, miR-137-3p, bone marrow-derived mesenchymal stem cells, CXCL12 (SDF-1α), Runx2, endothelial progenitor cells

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“…The buffy coat extract contains bone marrow cells, MSCs, osteoprogenitor cells, and growth factors [9]. In 2017, we reported the results of CABMAT after a mean follow-up period of 5 years in patients with asymptomatic ONFH [10, 11]. This study aimed to report the results of management of ONFH with CABMAT for > 10 years.…”

Section: Introductionmentioning

confidence: 99%

Ten-year results of concentrated autologous bone marrow aspirate transplantation for osteonecrosis of the femoral head: a retrospective study

Tomaru

Yoshioka

Sugaya

et al. 2019

BMC Musculoskelet Disord

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Background Idiopathic osteonecrosis of the femoral head (ONFH) occurs at a relatively younger age. It is therefore important to prevent the resultant femoral head collapse and requirement of total hip arthroplasty in these patients. In 2003, we initiated concentrated autologous bone marrow aspirate transplantation (CABMAT), a joint-preserving treatment for ONFH, at our institution. Here, we report the long-term results of CABMAT treatment. Methods We retrospectively collated and analyzed the demographic and treatment data of 69 patients (109 hips) with idiopathic ONFH treated with CABMAT between April 2003 and April 2008. Results Totally, 44 patients (21 men, 23 women, 80 hips) completed the 10-year follow-up. The follow-up rate was 73.4%, and the mean follow-up period was 12.0 (range, 10.0–15.4) years. The mean age of the patients was 42.2 (range, 16.3–70.5) years. Using the Association Research Circulation Osseous (ARCO) classification system for preoperative analysis, 12, 31, 32, and 5 hips were classified as stages 1, 2, 3, and 4, respectively. The overall rate of conversion to total hip arthroplasty (THA) was 34% (27/80 hips). In a multivariate regression analysis, the preoperative stage of ONFH and the body mass index were found to correlate significantly with conversion to THA. Totally, 43 hips (of 80) were classified as belonging to the pre-collapse stage (i.e., stages 1 or 2). The overall collapse rate and the THA-conversion rate of these hips were estimated to be 49% (21/43) and 14% (6/43), respectively. Conclusions On the basis of our long-term findings, the minimally invasive and feasible CABMAT therapy can be utilized as one of a joint-preserving treatment for ONFH.

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Mid-term results of concentrated autologous bone marrow aspirate transplantation for corticosteroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus

Cited by 16 publications

References 25 publications

Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

Silencing MicroRNA-137-3p, which Targets RUNX2 and CXCL12 Prevents Steroid-induced Osteonecrosis of the Femoral Head by Facilitating Osteogenesis and Angiogenesis

Ten-year results of concentrated autologous bone marrow aspirate transplantation for osteonecrosis of the femoral head: a retrospective study

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