Sex Differences in Mesenchymal Stem Cell Therapy With Gelatin-Based Microribbon Hydrogels in a Murine Long Bone Critical-Size Defect Model

Frontiers in Bioengineering and Biotechnology

Stuart B. Goodman¹  Fan Yang¹  Joy Y. Wu²  Masaya Ueno³  Tzuhua Lin⁴  Takeshi Utsunomiya⁴  Masahiro Maruyama⁴  Zhenyu Yao⁴  Ning Zhang⁴  Ejun Huang⁴  Huaishuang Shen⁴  Hirohito Hirata⁴  Danial Barati⁴  Stefan Zwingenberger⁵ 

[1] Department of Bioengineering, Stanford University, Stanford, CA, United States;Department of Medicine, Stanford University, Stanford, CA, United States;Department of Orthopaedic Surgery, Faculty of Medicine, Saga University, Saga, Japan;Department of Orthopaedic Surgery, Stanford University, Stanford, CA, United States;University Center for Orthopaedics, Traumatology, and Plastic Surgery, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany;

关键词: sex differences;    bone healing;    mesenchymal stem cell;    microribbon hydrogel;    interleukin-4;   

DOI  :  10.3389/fbioe.2021.755964

来源: DOAJ

【 摘 要 】

Mesenchymal stem cell (MSC)-based therapy and novel biomaterials are promising strategies for healing of long bone critical size defects. Interleukin-4 (IL-4) over-expressing MSCs within a gelatin microribbon (µRB) scaffold was previously shown to enhance the bridging of bone within a critical size femoral bone defect in male Balb/c mice. Whether sex differences affect the healing of this bone defect in conjunction with different treatments is unknown. In this study, we generated 2-mm critical-sized femoral diaphyseal bone defects in 10–12-week-old female and male Balb/c mice. Scaffolds without cells and with unmodified MSCs were implanted immediately after the primary surgery that created the bone defect; scaffolds with IL-4 over-expressing MSCs were implanted 3 days after the primary surgery, to avoid the adverse effects of IL-4 on the initial inflammatory phase of fracture healing. Mice were euthanized 6 weeks after the primary surgery and femurs were collected. MicroCT (µCT), histochemical and immunohistochemical analyses were subsequently performed of the defect site. µRB scaffolds with IL-4 over-expressing MSCs enhanced bone healing in both female and male mice. Male mice showed higher measures of bone bridging and increased alkaline phosphatase (ALP) positive areas, total macrophages and M2 macrophages compared with female mice after receiving scaffolds with IL-4 over-expressing MSCs. Female mice showed higher Tartrate-Resistant Acid Phosphatase (TRAP) positive osteoclast numbers compared with male mice. These results demonstrated that sex differences should be considered during the application of MSC-based studies of bone healing.

【 授权许可】

Unknown