Local transplantation of human multipotent adipose-derived stem cells accelerates fracture healing via enhanced osteogenesis and angiogenesis

Abstract

Adipose tissue is one of the promising sources of multipotent stem cells in human. Human multipotent adipose-derived stem (hMADS) cells have recently been isolated and showed differentiation potential into multiple mesenchymal lineages in vitro and in vivo. On the basis of these evidences, we examined the therapeutic efficacy of hMADS cells for fracture healing in an immunodeficient rat femur non-union fracture model. Local transplantation of hMADS cells radiographically and histologically promoted fracture healing with significant improvement of biomechanical function at the fracture sites compared with local transplantation of human fibroblasts (hFB) or PBS administration. Histological capillary density and physiological blood flow by laser Doppler perfusion imaging were significantly greater in hMADS group than hFB and PBS groups. Expressions of intrinsic (rat) bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and angiopoietin-1 in peri-fracture tissue were upregulated in hMADS group than other groups. In addition, presence of BMP-2 or VEGF activated the proliferation and migration of hMADS cells in vitro. These results indicate that hMADS cells stimulate the interaction between the transplanted cells and the resident cells stronger than other cells, and they promote fracture healing more effectively. Furthermore, immunohistochemistry for human-specific antibodies revealed direct differentiation of hMADS cells into osteoblasts or endothelial cells in newly formed callus or vasculature, respectively. RT-PCR for human-specific primers for osteogenic/endothelial markers also disclosed osteogenic and vasculogenic plasticity of the transplanted hMADS cells at the early stage of fracture healing. The present results suggest that transplantation of hMADS cells may become a useful strategy for cell-based bone regeneration in the future clinical setting.

Uncultured Autogenous Adipose-derived Regenerative Cells Promote Bone Formation During Distraction Osteogenesis in Rats

“…Although ADSCs can survive a long period and undergo osteogenic differentiation in vivo [10], they may also contribute through paracrine pathways. The adiposederived cells secrete angiogenic cytokines such as BMP-2, VEGF, SDF-1, and IL-6, which are postulated to contribute to the osteogenic and angiogenic properties of ASDCs [14,16]. Our study supports these existing data both in terms of the survival potential and paracrine effects of ADRCs.…”

Mesenchymal stem cells derived from vertebrae (vMSCs) show best biological properties

“…Bone marrow-derived MSCs, combined with biomaterial scaffolds (hydroxyapatite, b-tricalcium phosphate, demineralized bone matrix), were successfully used to achieve spine fusion in comparison with conventional iliac crest bone autograft [19][20][21][22]. Although most of the studies involve MSCs derived from bone marrow, some authors have recently shown that MSCs derived from adipose tissue can efficiently promote bone regeneration in animal models for the healing of femoral or vertebral fractures [23,24] and for the acceleration of spinal arthrodesis [25]. As the adipose tissue can be found in abundance with reduced donor site morbidity, the problems associated to bone marrow harvesting could be overcome.…”

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization

“…29 Mouse KSLs or OBs (5 Â 10 4 cells per well) were seeded onto upper chambers in 24-well Transwell culture plates (Corning Incorporated Life Science, MA, USA) and lower chambers were filled with DMEM with 10% FBS containing 50 ng/ml of SDF-1a (Minneapolis, MN, USA) followed by incubation for 6 h at 37 1C in 5% CO 2 . Migrated cells were stained with 4',6-diamidino-2-phenylindole (DAPI) and counted under a fluorescent microscope.…”