Background. Bone marrow contains various kinds of primitive cells which differentiate into endothelial cells and could secrete several growth factors. Therefore, we attempted to induce therapeutic angiogenesis using self bone marrow cells in a rat model. Materials and methods. Quantitative angiogenesis was examined using a sponge implantation assay that indicated whether the rat bone marrow cells had induced angiogenesis or not. Employing a rat ischemic heart model, bone marrow cells were injected directly into the ischemic area and the number of vessels was examined immunohistochemically using the anti-CD31 monoclonal antibody. The contributed growth factors revealed the levels present in the ischemic myocardium by an enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Results. The sponge implantation assay showed that bone marrow cells induced angiogenesis. Light microscopic analysis of the vessel count positively stained by anti-CD31 in the ischemic area showed that angiogenesis had been induced to a significantly greater degree in the group implanted with bone marrow cells (BMI group) than in the group injected with phosphate-buffered saline (PBS group) 1 week after BMI. Levels of the inflammatory cytokines interleukin-1 (IL-1beta) and cytokine-induced neutrophil chemoattractant (CINC) in the BMI group were significantly elevated compared with those in the PBS group. Conclusions. Self bone marrow cell implantation induced angiogenesis in a rat ischemic heart model as a result of elevation of the levels of IL-1beta and CINC. Thus, bone marrow implantation could be a novel and simple method to induce therapeutic angiogenesis.
Copyright 2000 Academic Press.