Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspirated from long-bone fracture patients with normal healing (U) or non-united (NU). Uncultured (native) CD271highCD45low cells or passage-zero cultured BM-MSCs were analyzed for gene expression levels, and functional assays were conducted using culture-expanded BM-MSCs. Blood samples were analyzed for serum cytokine levels. Uncultured NU-CD271highCD45low cells significantly expressed fewer transcripts of growth factor receptors, EGFR, FGFR1, and FGRF2 than U cells. Significant fewer transcripts of alkaline phosphatase (ALPL), osteocalcin (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were detected in NU-CD271highCD45low cells. Additionally, immunoregulation-related markers were differentially expressed between NU- and U-CD271highCD45low cells. Interestingly, passage-zero NU BM-MSCs showed low expression of immunosuppressive mediators. However, culture-expanded NU and U BM-MSCs exhibited comparable proliferation, osteogenesis, and immunosuppression. Serum cytokine levels were found similar for NU and U groups. Collectively, native NU-BM-MSCs seemed to have low proliferative and osteogenic capacities; therefore, enhancing their quality should be considered for regenerative therapies. Further research on distorted immunoregulatory molecules expression in BM-MSCs could potentially benefit the prediction of complicated fracture healing.

Background: Research has suggested that bone fractures can hinder the health status of patients’ life. However, limited research has examined the impact that the healing process of a fracture has on the physical health and psychological state of individuals, particularly in considering the short- and long-term impact of having a fracture that fails to heal and drops into a non-union. The aim of this systematic review is to better understand the impact of fracture non-union to physical health and to respective psychological outcomes. Methods: Electronic databases ‘PubMed’, ‘Cochrane’, ‘PsycInfo’, ‘Medline’, ‘Embase’, ‘Web of Science’, and ‘CINAHL’ were used. Search terms used were nonunion OR non-union OR “non union” OR “long bone” OR “delayed union” AND “quality of life” OR qol OR depression OR anxiety OR psycholog* OR PTSD OR “post-traumatic stress disorder”. Studies published in the years 1995 to 2018 were included. Two independent reviewers carried out screening and data extraction. Studies were included if (1) participants were adult (human) patients with a traumatic non-union secondary to fracture/s; (2) outcomes measured included physical health and psychological wellbeing (e.g., PTSD, psychological trauma, depression, anxiety, etc.). Studies received emphasis if they compared those outcomes between: (1) The “non-union” group to a normative, matched population and (2) the “non-union group” to the same group after union was achieved. However, studies that did not use comparison groups were also included. Results: Out of the 1896 papers identified from our thorough literature search, 13 met the inclusion criteria. Quality assessment was done by the Methodological Index for Non-Randomized Studies (MINORS). Findings suggested that non-unions had a detrimental impact on physical health, and psychological difficulties often after recovery. Conclusions: Patients who experience a long bone non-union are at risk of greater psychological distress and lower physical health status. There is a need for early identification of psychological distress in patients with fracture non-unions and psychological provision should become part of the available treatment.

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