Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10756930 | Biochemical and Biophysical Research Communications | 2014 | 6 Pages |
Abstract
Peripheral blood mononuclear cell (PBMNC) is one of powerful tools for therapeutic angiogenesis in hindlimb ischemia. However, traditional approaches with transplanted PBMNCs show poor therapeutic effects in severe ischemia patients. In this study, we used autograft models to determine whether hypoxic pretreatment effectively enhances the cellular functions of PBMNCs and improves hindlimb ischemia. Rabbit PBMNCs were cultured in the hypoxic condition. After pretreatment, cell adhesion, stress resistance, and expression of angiogenic factor were evaluated in vitro. To examine in vivo effects, we autografted preconditioned PBMNCs into a rabbit hindlimb ischemia model on postoperative day (POD) 7. Preconditioned PBMNCs displayed significantly enhanced functional capacities in resistance to oxidative stress, cell viability, and production of vascular endothelial growth factor. In addition, autologous transplantation of preconditioned PBMNCs significantly induced new vessels and improved limb blood flow. Importantly, preconditioned PBMNCs can accelerate vessel formation despite transplantation on POD 7, whereas untreated PBMNCs showed poor vascularization. Our study demonstrated that hypoxic preconditioning of PBMNCs is a feasible approach for increasing the retention of transplanted cells and enhancing therapeutic angiogenesis in ischemic tissue.
Keywords
DAPIPBMNCCXCR4RT-PCRGAPDHDcf4′,6-diamidino-2-phenylindole dihydrochlorideHypoxic preconditioningROSPre-clinical testingTherapeutic angiogenesisCell-based therapyPeripheral blood mononuclear cellC-X-C chemokine receptor type 4reverse transcription-polymerase chain reactionglyceraldehyde-3-phosphate dehydrogenaseReactive oxygen species
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Authors
Tomoaki Kudo, Tohru Hosoyama, Makoto Samura, Shunsaku Katsura, Arata Nishimoto, Naruji Kugimiya, Yasuhiko Fujii, Tao-Sheng Li, Kimikazu Hamano,