PMID- 26021713 OWN - NLM STAT- MEDLINE DCOM- 20160204 LR - 20220330 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 6 IP - 1 DP - 2015 May 29 TI - Efficacy of autologous stem cell-based therapy for osteonecrosis of the femoral head in sickle cell disease: a five-year follow-up study. PG - 110 LID - 10.1186/s13287-015-0105-2 [doi] LID - 110 AB - INTRODUCTION: 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. However, whether this decrease also extends to the early stages of ONFH in sickle cell disease (SCD) is still unclear. METHODS: We 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. RESULTS: At 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. CONCLUSION: The 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 REGISTRATION: ClinicalTrials.gov NCT02448121; registered 15 May 2015. FAU - Daltro, Gildasio Cerqueira AU - Daltro GC AD - Prof. Edgar Santos Hospital Complex, Salvador, BA, 40110-902, Brazil. gildasio.daltro@yahoo.com.br. FAU - Fortuna, Vitor AU - Fortuna V AD - Health Science Institute, Federal University of Bahia, Reitor Miguel Calmon Avenue, Salvador, BA, 40110-100, Brazil. vfort@ufba.br. FAU - de Souza, Eliane Silva AU - de Souza ES AD - Health Science Institute, Federal University of Bahia, Reitor Miguel Calmon Avenue, Salvador, BA, 40110-100, Brazil. elifarufba@yahoo.com.br. FAU - Salles, Marcela Miranda AU - Salles MM AD - Health Science Institute, Federal University of Bahia, Reitor Miguel Calmon Avenue, Salvador, BA, 40110-100, Brazil. celafarma@yahoo.com.br. FAU - Carreira, Ana Claudia AU - Carreira AC AD - Cell and Molecular Therapy Center NUCEL-NETCEM, School of Medicine, Internal Medicine Department, and Chemistry Institute, Biochemistry Department, University of Sao Paulo, Sao Paulo, SP, 05508-900, Brazil. ancoc@iq.usp.br. FAU - Meyer, Roberto AU - Meyer R AD - Health Science Institute, Federal University of Bahia, Reitor Miguel Calmon Avenue, Salvador, BA, 40110-100, Brazil. rmeyer@ufba.br. FAU - Freire, Songeli Menezes AU - Freire SM AD - Health Science Institute, Federal University of Bahia, Reitor Miguel Calmon Avenue, Salvador, BA, 40110-100, Brazil. songeli.mf@gmail.com. FAU - Borojevic, Radovan AU - Borojevic R AD - Petropolis School of Medicine/Arthur de Sa Earp Faculties, Petropolis, RJ, 25680-120, Brazil. rrborojevic@gmail.com. AD - National Institute of Metrology, Quality and Technology (Inmetro), Xerem, Rio de Janeiro, RJ, 25250-020, Brazil. rrborojevic@gmail.com. LA - eng SI - ClinicalTrials.gov/NCT02448121 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150529 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (Antigens, CD) RN - 0 (Cytokines) SB - IM MH - Adipogenesis MH - Adolescent MH - Adult MH - Anemia, Sickle Cell/*complications MH - Antigens, CD/metabolism MH - Bone Marrow Cells/*cytology MH - Chondrogenesis MH - Cytokines/analysis MH - Female MH - Femur Head Necrosis/complications/*therapy MH - Follow-Up Studies MH - Hip/diagnostic imaging MH - Humans MH - Immunophenotyping MH - Male MH - Middle Aged MH - Osteogenesis MH - Radiography MH - *Stem Cell Transplantation MH - Stem Cells/*cytology/metabolism MH - Transplantation, Autologous MH - Young Adult PMC - PMC4465459 EDAT- 2015/05/30 06:00 MHDA- 2016/02/05 06:00 PMCR- 2015/05/29 CRDT- 2015/05/30 06:00 PHST- 2014/12/11 00:00 [received] PHST- 2015/05/21 00:00 [accepted] PHST- 2015/04/08 00:00 [revised] PHST- 2015/05/30 06:00 [entrez] PHST- 2015/05/30 06:00 [pubmed] PHST- 2016/02/05 06:00 [medline] PHST- 2015/05/29 00:00 [pmc-release] AID - 10.1186/s13287-015-0105-2 [pii] AID - 105 [pii] AID - 10.1186/s13287-015-0105-2 [doi] PST - epublish SO - Stem Cell Res Ther. 2015 May 29;6(1):110. doi: 10.1186/s13287-015-0105-2.