Groenewegen Hendrik C, Onuta Geanina, Goris Maaike, Zandvoort André, Zijlstra Felix, van Gilst Wiek H, Rozing Jan, de Smet Bart J G L, Roks Anton J M, Hillebrands Jan-Luuk
Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Vasc Res. 2008;45(6):493-502. doi: 10.1159/000127440. Epub 2008 Apr 23.
To determine the contribution of bone marrow (BM)-derived cells in in-stent restenosis (ISR) and transplant arteriosclerosis (TA).
Non-transgenic rats WT F344(TG) (n = 3) received stent implantation 6 weeks after lethal total body irradiation and suppletion with bone marrow from a R26-hPAP transgenic rat. After 4 weeks the abdominal aortas were harvested, the stent was quickly removed, the abdominal aorta was snap-frozen in liquid nitrogen and 5 mum cryosections for stainings were cut. Additionally, DA aortic allografts were transplanted into WT F344(TG) (n = 3) and R26-hPAP(WT) (n = 3) BM-chimeric recipients. Immunohistochemistry (hPAP staining) and immunofluorescence (hPAP, alpha-SMA and OX1) was performed on all sections.
Few hPAP-positive cells were observed in the neointima. Double stainings of hPAP-positive areas showed no alpha-SMA colocalization; OX-1 did show colocalization.
Non-BM-derived cells are the predominant source of neointimal cells in ISR and TA. Vascular wall-derived progenitor cells may rather be the source of SMCs that contribute to ISR and TA, which may have implications for our quest for new therapeutic targets to treat these vasculopathies.
确定骨髓（BM）来源的细胞在支架内再狭窄（ISR）和移植动脉硬化（TA）中的作用。
非转基因大鼠WT F344（TG）（n = 3）在致死性全身照射6周后接受支架植入，并补充来自R26-hPAP转基因大鼠的骨髓。4周后，采集腹主动脉，迅速取出支架，将腹主动脉在液氮中速冻，并切成5μm的冰冻切片用于染色。此外，将DA主动脉同种异体移植物移植到WT F344（TG）（n = 3）和R26-hPAP（WT）（n = 3）骨髓嵌合受体中。对所有切片进行免疫组织化学（hPAP染色）和免疫荧光（hPAP、α-SMA和OX1）检测。
在内膜中观察到少量hPAP阳性细胞。hPAP阳性区域的双重染色显示无α-SMA共定位；OX-1显示有共定位。
非BM来源的细胞是ISR和TA中内膜细胞的主要来源。血管壁来源的祖细胞可能是促成ISR和TA的平滑肌细胞的来源，这可能对我们寻找治疗这些血管病变的新治疗靶点有启示意义。
Zotero 插件