X-ray-visible microcapsules containing mesenchymal stem cells improve hind limb perfusion in a rabbit model of peripheral arterial disease.

X-ray-visible microcapsules containing mesenchymal stem cells improve hind limb perfusion in a rabbit model of peripheral arterial disease.
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DOI:
10.1002/stem.1096
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发表时间:
2012-06
期刊:
影响因子:
5.2
通讯作者:
Kraitchman, Dara L.
Kraitchman, Dara L.
中科院分区:
医学2区
文献类型:
--
作者:
Kedziorek, Dorota A.;Hofmann, Lawrence V.;Fu, Yingli;Gilson, Wesley D.;Cosby, Kenyatta M.;Kohl, Bernard;Barnett, Brad P.;Simons, Brian W.;Walczak, Piotr;Bulte, Jeff W. M.;Gabrielson, Kathleen;Kraitchman, Dara L.

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外周动脉疾病(PAD)患者的治疗目标是恢复缺血组织的血流。干细胞移植为促进动脉生成和血管新生提供了新的途径。细胞疗法的两个主要问题是细胞存活率差以及缺乏细胞递送和分布的可视化。为了解决这些治疗障碍,将同种异体骨髓来源的间充质干细胞(MSC)封装在浸渍有不透射线造影剂(MSC-Xcaps)的藻酸盐中。通过荧光测定法测定的体外MSC-Xcap活力较高(封装后30天为96.9% ± 2.7%),在临床X射线荧光系统上仅可观察到10个Xcap。使用血管内PAD模型,将家兔(n = 21)在闭塞后24小时在缺血性大腿中随机接受MSC-Xcaps(n = 6)、空Xcaps(n = 5)、未包封的MSC(n = 5)或假肌肉注射(n = 5)。在MSC移植后立即和14天后,在临床血管造影系统上获得的数字X射线照片显示了Xcap注射部位的持续可视化,保留了对比度噪声。使用改良的TIMI帧计数,定量血管造影显示MSC-Xcap治疗动物与空Xcap相比,后肢灌注或动脉生成改善65%。通过抗-CD 31染色的血管密度的死后免疫组织病理学证实,与空Xcaps相比,Xcap-MSC处理的动物中血管生成增强87%。MSC-Xcaps代表了第一种X射线可见的细胞治疗剂,具有增强的PAD治疗效果。
The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow-derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC-Xcaps.) In vitro MSC-Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x-ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC-Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast-to-noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC-Xcap-treated animals versus empty Xcaps. Post-mortem immunohistopathology of vessel density by anti-CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap-MSC-treated animals versus empty Xcaps. MSC-Xcaps represent the first x-ray-visible cellular therapeutic with enhanced efficacy for PAD treatment.
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