title: Mesenchymal stem cell-conditioned medium facilitates angiogenesis and fracture healing in diabetic rats.
abstract: The most critical factor for fracture union is the blood supply to the fracture site, which is usually impaired in patients with diabetes. Recently, mesenchymal stem cells-derived conditioned medium (MSC-CM) has shown significantly higher levels of angiogenic factors, such as VEGF and IL-6. We demonstrate in this report that MSC-CM delivered in gelatin sponges stimulates angiogenesis and promotes fracture healing in a diabetic rat model. Subcutaneous implantation of gelatin sponges soaked in MSC-CM demonstrated better tissue ingrowth and higher capillary densities at 2 and 3 weeks than gelatin sponges in minimal essential medium (MEM) or 293 cell-derived conditioned medium (293-CM). Implantation of fibular defects with gelatin sponges soaked in MSC-CM enhanced bone ingrowth and fracture healing rates compared to 293-CM and MEM groups at 8 weeks. Micro-computed tomography analysis further indicated a higher new bone volume in the MSC-CM group compared to the other diabetic groups. Histological analysis with CD31 immunostaining also revealed that MSC-CM increased endothelial cell counts compared to the other groups. Together, these results indicated that gelatin sponges used to deliver MSC-CM promote angiogenesis and fracture healing in a diabetic model and may be an alternative strategy for treating fracture non-union in patients with diabetes.
authors.affiliation: Institute of Biomedical Engineering, National Yang-Ming University, Taiwan, Republic of China.
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Wang
authors.forename: Hsiao-Bai
authors.initials: HB
authors.lastname: Yang
authors.forename: Han-Shui
authors.initials: HS
authors.lastname: Hsu
authors.forename: Ling-Lan
authors.initials: LL
authors.lastname: Chen
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Tsai
authors.forename: Kuo-Shu
authors.initials: KS
authors.lastname: Tsai
authors.forename: Tu-Lai
authors.initials: TL
authors.lastname: Yew
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Kao
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000818:Animals; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005360:Fibula / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D013311:Streptozocin; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin