Ageing attenuates bone healing by mesenchymal stem cells in a microribbon hydrogel with a murine long bone critical-size defect model

• DOI: 10.1186/s12979-022-00272-1
• Publication Date: 2022-03-12T10:02:58Z
• Authors: Hirohito Hirata; Ning Zhang; Masaya Ueno; Danial Barati; Junichi Kushioka; Huaishuang Shen; Masanori Tsubosaka; Masakazu Toya; Tzuhua Lin; Ejun Huang; Zhenyu Yao; Joy Y. Wu; Stefan Zwingenberger; Fan Yang; Stuart B. Goodman
• Keywords: Bone healing; 0301 basic medicine; Research; RC952-954.6; RC581-607; Microribbon hydrogel; 3. Good health; Ageing; 03 medical and health sciences; Geriatrics; interleukin-4; Immunologic diseases. Allergy; Mesenchymal stem cell

Despite the high incidence of fractures and pseudoarthrosis in aged population, a potential role for use mesenchymal stem cells (MSCs) treatment bone defects elderly patients has not been elucidated. Inflammation innate immune system, including macrophages, play crucial roles differentiation activation MSCs. We have developed lentivirus-transduced interleukin 4 (IL4) over-expressing MSCs (IL4-MSCs) to polarize macrophages an M2 phenotype promote healing established young murine critical size defect model. In current study, we explore IL4-MSCs mice.A 2 mm femoral diaphyseal was created fixed with external fixation device 15- 17-month-old male female BALB/c mice. Microribbon (µRB) scaffolds (Sc) or without encapsulation were implanted sites. Accordingly, mice divided into three groups: Sc-only, Sc + MSCs, IL4-MSCs. Mice euthanized six weeks after surgery; subsequently, MicroCT (µCT), histochemical immunohistochemical analyses performed.µCT analysis revealed that formation markedly enhanced IL4-MSC group. Compared amount new increased groups. However, no bridging observed all H&E staining showed fibrous tissue within Alkaline phosphatase (ALP) The group decrease number M1 increase significant M2/M1 ratio.IL4 promotes macrophage polarization phenotype, facilitating osteogenesis vasculogenesis. addition µRB scaffold polarized formation; however, complete any specimens. These results suggest are insufficient heal mice, as opposed younger animals. Additional therapeutic strategies needed this challenging clinical scenario.