Abstract
IntroductionStem cell therapy with bone marrow-derived mononuclear cells (BMMCs) is an option for improving joint function in osteonecrosis of the femoral head (ONFH). Bone marrow-derived mesenchymal stromal cell (MSC) numbers and their osteogenic differentiation are decreased in patients with ONFH. However, whether this decrease also extends to the early stages of ONFH in sickle cell disease (SCD) is still unclear.MethodsWe conducted a phase I/II, non-controlled study to determine efficacy and safety of BMMC implantation using a minimally invasive technique in SCD patients with ONFH. Eighty-nine patients were recruited and followed up for 60 months after surgery. Clinical and radiographic findings were assessed, and data were completed by in vitro analysis.ResultsAt the final follow-up (60 months) there was a significant improvement in clinical joint symptoms and pain relief as measured by the Harris Hip Score (P = 0.0005). In addition, after the BMMC implantation procedure, radiographic assessment showed disease stabilization and only 3.7 % of the treated patients did not achieve a satisfactory clinical result. The amount of fibroblast colony-forming units was 28.2 ± 13.9 per 1 million BMMCs after concentration. Flow cytometry analysis showed a significantly higher number of hematopoietic stem/endothelial progenitor cell markers in concentrated BMMCs when compared with bone marrow aspirate, indicating an enrichment of these cell types. Isolated MSCs from SCD patients with pre-collapse ONFH maintained the replicative capacity without significant loss of their specific biomolecular characteristics, multi-differentiation potential, and osteogenic differentiation activities. Cytokines and growth factors (interleukin-8, transforming growth factor-beta, stromal cell-derived factor-1alpha and vascular endothelial growth factor) that mediate endogenous bone regeneration were also produced by expanded MSCs from SCD patients.ConclusionThe autologous BMMC implantation with a minimally invasive technique resulted in significant pain relief and halted the progression of early stages of ONFH in SCD patients. MSCs from SCD patients display biological properties that may add to the efficiency of surgical treatment in ONFH. In summary, our results indicate that infusion of BMMCs enriched with stem/progenitor cells is a safe and effective treatment for the early stages of ONFH in SCD patients.Trial registrationClinicalTrials.gov NCT02448121; registered 15 May 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0105-2) contains supplementary material, which is available to authorized users.
Highlights
Stem cell therapy with bone marrow-derived mononuclear cells (BMMCs) is an option for improving joint function in osteonecrosis of the femoral head (ONFH)
Improved clinical outcome of femoral heads treated with BMMCs at early stages of osteonecrosis in sickle cell disease In the present study, we followed-up 89 SCD patients with osteonecrosis of femoral head (ONFH)
The current study demonstrated that pre-collapse stages of ONFH in SCD patients could be treated safely and efficiently with BMMCs enriched with stem/progenitor cells combined with minimally invasive decompression
Summary
Stem cell therapy with bone marrow-derived mononuclear cells (BMMCs) is an option for improving joint function in osteonecrosis of the femoral head (ONFH). Bone marrow-derived mesenchymal stromal cell (MSC) numbers and their osteogenic differentiation are decreased in patients with ONFH Whether this decrease extends to the early stages of ONFH in sickle cell disease (SCD) is still unclear. Osteonecrosis of the femoral head (ONFH) is a debilitating and severe complication of SCD and its treatment is still a big challenge. Patients with SCD experience both large and small vessel occlusions leading to end-organ damage and complications such as ONFH. These vascular occlusion events result from various processes including hypoxia-induced erythrocyte sickling, along with extravascular compression of the intra-osseous blood supply resulting in an imbalance between osteoblast formation and necrosis, which culminates in femoral head infarction [8]. Since ONFH most frequently occurs in young patients, a treatment preserving the femoral head instead of replacing it is preferable whenever possible
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