Structural integration and cardiovascular effects following transplantation of endothelial progenitor cells (EPCs) into the brainstem of rats

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Our evidence indicates that brainstem endothelium is a viable target for controlling arterial pressure. Thus, we have used EPCs to target the brainstem microvasculature in vivo and assessed any effect on cardiovascular function. Bone marrow mononuclear cells from male Wistar rats were expanded for 7–15 days in conditions appropriate for the endothelial lineage. EPCs were characterized by immunofluorescence staining, flow cytometry, and using the Matrigel assay for network formation. Fluorescently tagged EPCs were injected intraparenchymally into the nucleus tractus solitarii (NTS), a region regulating arterial pressure, of male Wistar rats. Experiments were terminated 16 days post‐injection. EPCs remained at the site of injection until animals were sacrificed. During this time, EPCs migrated away from the injection site becoming closely associated with the vasculature. Peak measurements occurred between 10 to 15 days post injection and included a reduction in: systolic pressure (SP)(−7±0.5 mmHg), low frequency spectra of SP (−19%±1.0‐ indicating reduced sympathetic vasomotor tone) and heart rate (−18±4.3 beats/min). Cardiac baroreflex sensitivity increased (22%±0.8). In conclusion, EPCs remain viable for at least 16 days when transplanted into the NTS in vivo, integrate into the vascular wall and alter cardiovascular autonomic function in normotensive rats. MRC & Pfizer funded research.

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