RESUMO
The Signature Series Symposium "Cellular Therapies for Orthopaedics and Musculoskeletal Disease Proven and Unproven Therapies-Promise, Facts and Fantasy" was held as a pre-meeting of the 26th International Society for Cellular Therapy (ISCT) annual congress in Montreal, Canada, May 2, 2018. This was the first ISCT program that was entirely dedicated to the advancement of cell-based therapies for musculoskeletal diseases. Cellular therapies in musculoskeletal medicine are a source of great promise and opportunity. They are also the source of public controversy, confusion and misinformation. Patients, clinicians, scientists, industry and government share a commitment to clear communication and responsible development of the field. Therefore, this symposium convened thought leaders from around the world in a forum designed to catalyze communication and collaboration to bring the greatest possible innovation and value to patients with musculoskeletal conditions.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Doenças Musculoesqueléticas/terapia , Animais , Terapia Baseada em Transplante de Células e Tecidos/normas , Fantasia , Humanos , Doenças Musculoesqueléticas/veterinária , Ortopedia , Medicina Regenerativa/métodos , Sociedades Científicas , Pesquisa Translacional Biomédica/legislação & jurisprudência , Pesquisa Translacional Biomédica/normas , Medicina Veterinária/métodosRESUMO
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is associated with regional loss of cells within bone, often resulting in pain and mechanical collapse. Our purpose was to analyze the cell-therapies used in clinical trials for the treatment of ONFH with regard to (1) cell-sources, (2) collection techniques, (3) cell-processing, (4) qualitative and quantitative characterizations, and (5) delivery methods. METHODS: A systematic review of the current literature on the use of cell therapies for the treatment of ONFH was performed. Studies with a level-of-evidence III or higher were evaluated. A total of 1483 articles were screened. Eleven studies met the criteria to be included in this review. RESULTS: Ten studies used bone-marrow, and 1 study used blood as the cell-source. Nine studies used freshly isolated tissue-derived nucleated cells from bone-marrow, mixed bone marrow-derived nucleated cells, 1 study used mixed blood-derived nucleated cells, and 1 study used culture-expanded cells derived from bone marrow aspirate. Cell dose varied from 2-million to 3-billion cells. Qualitative cell characterization of injected cells using surface markers was done by 5 studies using CD34. Two studies assayed the cell-population using a colony-forming-unit assay. CONCLUSION: There is a lack of standardization with respect to the quantitative and qualitative characterization of methods for cell-harvest, cell-processing, and cell-transplantation/delivery. Cell-therapy holds promise as a means of restoring local cell populations that are made deficient because of injury or disease. However, the orthopedic community and patients will benefit greatly by a greater investment in blinded, randomized, controlled trials and clinical effectiveness trials that embrace rigorous standards.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Necrose da Cabeça do Fêmur/terapia , Ensaios Clínicos como Assunto , Cabeça do Fêmur , Humanos , Transplante AutólogoRESUMO
BACKGROUND: Cell-therapy has been promoted among the therapeutic arsenal that can aid in bone formation and remodeling, in early stages of osteonecrosis of the femoral head (ONFH). The purpose of this systematic review was to assess the evidence supporting the (1) clinical efficacy; (2) structural modifying effect, as evaluated radiographically; (3) revision rates; and (4) safety of cell-therapy for the treatment of ONFH. METHODS: A systematic review was performed including studies with a level-of-evidence of III or higher. A total of 1483 articles were screened. Eleven studies met the criteria for inclusion in this review (level-of-evidence: 6 level-I, 1 level-II, and 4 level-III), including 683 cases of ONFH. RESULTS: All 10 studies that reported patient-reported outcomes showed improved outcomes in the cell-therapy groups compared with the control group. Overall, 24.5% (93/380 hips) that received cell-therapy showed radiographic progression compared with 40% (98/245 hips) in the control group. Nine of 10 studies that reported failure rates showed a lower total hip arthroplasty conversion rate in the cell-therapy group 16% (62/380 hips) compared with the control group 21% (52/252 hips). There was a low complication rate (<3%) with no major adverse effects. CONCLUSION: Cell-therapies for the treatment of ONFH have been reported to be safe and suggest improved clinical outcomes with lower disease progression rate. However, there was substantial heterogeneity in the included studies, and in the cell-based therapies used. Specific clinical indications and cell-therapy standardization are required because studies varied widely with respect to cell sourcing, cell characterization, adjuvant therapies, and assessment of outcomes.
Assuntos
Artroplastia de Quadril , Terapia Baseada em Transplante de Células e Tecidos/métodos , Necrose da Cabeça do Fêmur/cirurgia , Cabeça do Fêmur/cirurgia , Quadril/cirurgia , Adulto , Terapia Combinada , Progressão da Doença , Feminino , Cabeça do Fêmur/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Resultado do TratamentoRESUMO
The orthopedic field has experienced several major practice-changing pivotal shifts in the past several decades, such as the invention and application of the arthroscope or the implementation and advancement of joint arthroplasties. Most of these previous breakthroughs have focused on surgical techniques and devices. However, the next major advance in the field is likely to be related to biologic treatments. Although still in its early stage of development, orthopedic regenerative medicine, including cellular therapies, represents a great opportunity, since we are only beginning to understand their biological potential. The main challenge in this pathway is to translate the promising results obtained by basic scientists to clinical practice. This work reviewed the market and clinical evidence, as well as future perspectives, concerning cellular therapies in orthopedics.