Effect of Allogeneic Cell-Based Tissue-Engineered Treatments in a Sheep Osteonecrosis Model
Por:
Lopez-Fernandez, A, Barro, V, Ortiz-Hernandez, M, Manzanares, MC, Vivas, D, Vives, J, Velez, R, Ginebra, MP, Aguirre, M
Publicada:
1 sep 2020
Ahead of Print:
1 mar 2020
Resumen:
Osteonecrosis of the femoral head (ONFH) is defined as a tissue disorder and successive subchondral bone collapse resulting from an ischemic process, which may progress to hip osteoarthritis. Cell therapy with multipotent bone marrow mesenchymal stromal cells (BM-MSC) of autologous origin appears to be safe and has shown regenerative potential in previous preclinical and clinical studies. The use of allogeneic cells is far more challenging, but may be a promising alternative to use of autologous cells. Moreover, an optimized dosage of cells from an allogeneic source is needed to obtain off-the-shelf tissue engineering products (TEPs). The purpose of this study was to evaluate the efficacy of a TEP composed of undifferentiated ex vivo expanded BM-MSC of allogeneic origin, combined with bone matrix particles in variable doses. A comparative analysis of TEP's bone regenerative properties against its autologous counterpart was performed in an early-stage ONFH preclinical model in mature sheep. Allogeneic BM-MSC groups demonstrated bone regeneration capacity in osteonecrotic lesions equivalent to autologous BM-MSC groups 6 weeks after treatment. Likewise, stimulation of bone regeneration by a low cell dose of 0.5 x 10(6) BM-MSC/cm(3) was equivalent to that of a high cell dose, 5 x 10(6) BM-MSC/cm(3). Neither local nor systemic immunological reactions nor tumorigenesis were reported, strengthening the safety profile of allogeneic BM-MSC therapy in this model. Our results suggest that low-dose allogeneic BM-MSC is sufficient to promote bone regeneration in femoral head osteonecrotic lesions, and should be considered in translation of new allogeneic cell-based TEPs to human clinics.
Impact statement
Cell therapy and tissue engineering hold promise as novel regenerative therapies for musculoskeletal diseases, and particularly in bone regeneration strategies. In this article, we report the evaluation of the efficacy of an allogeneic cell-based tissue engineering product (TEP) in an early-stage osteonecrosis of the femoral head preclinical model in skeletally mature sheep. Moreover, we demonstrate its bone regeneration capacity and safety in vivo and its equivalence to autologous counterparts. These findings have important implications for the translation of new allogeneic cell-based TEPs to human clinics.
Filiaciones:
Lopez-Fernandez, A:
Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Musculoskeletal Tissue Engn Grp, Passeig Vall dHebron 129-139, Barcelona 08035, Spain
Barro, V:
Hosp Univ Vall dHebron, Orthoped Surg Dept, Barcelona, Spain
Ortiz-Hernandez, M:
Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp BBT, Barcelona, Spain
Manzanares, MC:
Univ Barcelona, Dept Pathol & Expt Therapeut, Human Anat & Embryol Unit, Barcelona, Spain
Vivas, D:
Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Musculoskeletal Tissue Engn Grp, Passeig Vall dHebron 129-139, Barcelona 08035, Spain
Banc Sang & Teixits, Serv Terapia Cellular, Barcelona, Spain
Vives, J:
Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Musculoskeletal Tissue Engn Grp, Passeig Vall dHebron 129-139, Barcelona 08035, Spain
Banc Sang & Teixits, Serv Terapia Cellular, Barcelona, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
Velez, R:
Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Musculoskeletal Tissue Engn Grp, Passeig Vall dHebron 129-139, Barcelona 08035, Spain
Hosp Univ Vall dHebron, Orthoped Surg Dept, Barcelona, Spain
Ginebra, MP:
Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp BBT, Barcelona, Spain
Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona, Spain
Aguirre, M:
Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Musculoskeletal Tissue Engn Grp, Passeig Vall dHebron 129-139, Barcelona 08035, Spain
Hosp Univ Vall dHebron, Orthoped Surg Dept, Barcelona, Spain
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