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Mesenchymal stromal cells for osteonecrosis.

ABSTRACT: Osteonecrosis (ON) is an acquired debilitating skeletal disorder, which is caused by a multitude of traumatic and non-traumatic etiological factors. Vascular damage, mechanical stress and increased intraosseous pressure have been discussed as contributors to ON. The optimal treatment of ON remains to be determined, since the current gold standard, core decompression, is insufficiently effective. Specific properties of mesenchymal stromal cells (MSCs) provide the rationale for their assessment in advanced stages of ON: Osteoinductive potential has been demonstrated and MSC preparations of suitable quality for use as medicinal products have been developed. Here we review the scant information on the use of allogeneic or autologous MSCs in advanced ON as well as potentially supportive data from pre-clinical studies with autologous bone marrow mononuclear cells (auto BM-MNCs), which have been studied quite extensively and the presumed therapeutic effect of which was attributed to the rare MSCs contained in these cell products. Outcomes in clinical trials with MSCs and auto-BM-MNCs remain preliminary and non-definitive, at best promising, with respect to their pharmacological effect. Clearly, though, the application of any of these cell therapies was technically feasible and safe in that it was associated with low complication rates. The heterogeneity of cell type and source, study protocols, cell manufacturing, cell properties, cell doses and surgical techniques might contribute to inconsistent results.

SUBMITTER: Elgaz S

PROVIDER: S-EPMC7576732 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Mesenchymal stromal cells for osteonecrosis.

Elgaz S S Bonig H H Bader P P

Journal of translational medicine 20201020 1

Osteonecrosis (ON) is an acquired debilitating skeletal disorder, which is caused by a multitude of traumatic and non-traumatic etiological factors. Vascular damage, mechanical stress and increased intraosseous pressure have been discussed as contributors to ON. The optimal treatment of ON remains to be determined, since the current gold standard, core decompression, is insufficiently effective. Specific properties of mesenchymal stromal cells (MSCs) provide the rationale for their assessment in ...[more]

PMID: 33081809

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Project description:Bone forage to treat early osteonecrosis of the femoral head (ONFH) has evolved as the channel to percutaneously deliver cell therapy into the femoral head. However, its efficacy is variable and the drivers towards higher efficacy are currently unknown. The aim of this study was to evaluate the forage technique and correlate it with the efficacy to heal ONFH in a multicentric, multinational clinical trial to implant autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSCs).MethodsIn the context of EudraCT 2012-002010-39, patients with small and medium-sized (mean volume = 13.3%, range: 5.4 to 32.2) ONFH stage II (Ficat, ARCO, Steinberg) C1 and C2 (Japanese Investigation Committee (JIC)) were treated with percutaneous forage and implantation of 140 million BM-hMSCs in a standardized manner. Postoperative hip radiographs (AP-anteroposterior and lateral), and MRI sections (coronal and transverse) were retrospectively evaluated in 22 patients to assess the femoral head drilling orientation in both planes, and its relation to the necrotic area.ResultsTreatment efficacy was similar in C1 and C2 (coronal plane) and in anterior to posterior (transverse plane) osteonecrotic lesions. The drill crossed the sclerotic rim in all cases. The forage was placed slightly valgus, at 139.3 ± 8.4 grades (range, 125.5-159.3) with higher dispersion (f = 2.6; p = 0.034) than the anatomical cervicodiaphyseal angle. Bonferroni's correlation between both angles was 0.50 (p = 0.028). More failures were seen with a varus drill positioning, aiming at the central area of the femoral head, outside the weight-bearing area (WBA) (p = 0.049). In the transverse plane, the anterior positioning of the drill did not result in better outcomes (p = 0.477).ConclusionThe forage drilling to deliver cells should be positioned within the WBA in the coronal plane, avoiding varus positioning, and central to anterior in the transverse plane. The efficacy of delivered MSCs to regenerate bone in ONFH could be influenced by the drilling direction. Standardization of this surgical technique is desirable.

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Mesenchymal stromal cells for osteonecrosis.

Publications

Mesenchymal stromal cells for osteonecrosis.

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