Title |
Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection
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Published in |
Stem Cell Research & Therapy, April 2015
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DOI | 10.1186/s13287-015-0036-y |
Pubmed ID | |
Authors |
Angélique Lebouvier, Alexandre Poignard, Madeleine Cavet, Jérôme Amiaud, Julie Leotot, Philippe Hernigou, Alain Rahmouni, Philippe Bierling, Pierre Layrolle, Hélène Rouard, Nathalie Chevallier |
Abstract |
Osteonecrosis of the femoral head (ONFH) is a degenerative disease progressing to a femoral head (FH) collapse. Injection of osteoprogenitor cells like bone marrow mesenchymal stromal cells (BMSCs) into the FH appears to be a good therapeutic treatment. However, safety and efficacy of BMSCs to treat bone defect are the main preclinical data required for clinical application. Efficacy and no risk of cells transformation after amplification of BMSCs have been extensively described. The main objectives of this study were to develop a simple and usable procedure for clinicians and control its feasibility by evaluating the biodistribution of BMSCs after injection into the FH in a large animal model. The impact of this approach was evaluated on one natural pig ONFH. BMSCs were directly injected in the pig FH, then the biodistribution of grafted cells were detected either by qPCR, cytometry or by combination of classical histology analysis and in situ hybridization (ISH). BMSCs' efficacy on bone regeneration was evaluated by MRI and histology. After 30 min and 24 h follow-up, grafted cells were detected at the injection site and no BMSCs were detected in filters organs or body fluids. Combination of classical histology analysis and ISH showed a good homogeneity of cells distribution in FH. Local delivery of BMSCs onto a bone scaffold associated to bone formation in vivo confirmed the preferential tropism of BMSCs to the bone tissue as well as their efficacy to form bone. Treatment of a natural pig ONFH by autologous BMSCs indicated a beginning of bone healing as soon as 2 weeks with a complete healing after 9 weeks. At this stage, MRI and histological analysis were similar to a normal FH. Intra-osseous injection of BMSCs in FH seems to be a good strategy for ONFH treatment as the safety concerning the biodistribution of BMSCs is ensured. Moreover, the efficacy of BMSCs in natural ONFH seems a promising approach. Altogether, these results constitute the preclinical data necessary for the setup of a clinical application with expanded BMSCs in the context of Advanced Therapies Medicinal Products. |
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Mendeley readers
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Student > Ph. D. Student | 8 | 12% |
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Veterinary Science and Veterinary Medicine | 2 | 3% |
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