Predictors of fracture healing in patients with recalcitrant nonunions treated with autologous culture expanded bone marrow‐derived mesenchymal stromal cells

• Published in: Journal of orthopaedic research Vol. 37; no. 6; pp. 1303 - 1309
• Main Authors: Bhattacharjee, Atanu, Kuiper, Jan H., Roberts, Sally, Harrison, Paul E., Cassar‐Pullicino, Victor N., Tins, Bernhard, Bajada, Stefan, Richardson, James B.
• Format: Journal Article
• Language: English
• Published: United States John Wiley and Sons Inc 01.06.2019
• Subjects: Adolescent; Adult; Aged; biomaterials; bone; bone biology; bone fracture; bone tissue engineering and repair; Cells, Cultured; Female; Fracture Healing - physiology; Fractures, Ununited - physiopathology; Fractures, Ununited - psychology; Humans; Logistic Models; Male; Mesenchymal Stem Cell Transplantation - adverse effects; Middle Aged; progenitors and stem cells; Prospective Studies; Quality of Life; Transplantation, Autologous; Young Adult; bone tissue engineering and repair; progenitors and stem cells; bone; biomaterials; bone biology; bone fracture
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1002/jor.24184

ABSTRACT The study reports the prospective outcome of treating severe recalcitrant fracture nonunion in patients with autologous bone marrow‐derived mesenchymal stromal cells (BMSC) from 2003 to 2010 and analyze predictors of union. Autologous BMSC were culture expanded and inserted at nonunion site with or without carriers in addition to surgical stabilization of the fracture. Radiological union was ascertained by musculoskeletal radiologists on plain radiographs and/or CT scans. A logistic regression analysis was performed with cell‐expansion parameters (cell numbers, cell doubling time) and known clinical factors (e.g., smoking and diabetes) as independent variables and fracture union as the dependent variable to identify the factors that influence bony healing. An Eq5D index score assessed the effect of treatment on general quality of health. A total of 35 patients (mean age 51+/−13 years) with established nonunion (median 2.9 years, 1–33) and, at least one failed nonunion surgery (median 4,1–14) received treatment. Fracture union was achieved in 21 patients (60%; 95%CI 44–75) at 2.6 years. Multiple penalized logistic regression revealed faster cell doubling time (p = 0.07), absence of diabetes (p = 0.003), less previous surgeries (p = 0.008), and lower age at cell implantation (p = 0.02) were significant predictors for fracture union. A significant increase in Eq5D index (p = 0.01) was noted with a mean rise of the score by 0.34 units (95%CI 0.11–0.58) at 1 year following the study. In summary, the study revealed cell doubling time as a novel in vitro parameter in conjunction with age, multiple surgeries, and diabetes as being significant predictors of the fracture union. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res 37:1303–1309, 2019.