Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
Cytotherapy. 2011 Feb;13(2):179-92. doi: 10.3109/14653249.2010.515579. Epub 2010 Sep 15.
The treatment of peripheral vascular disease (PVD) with stem cells potentially offers a promising strategy. We tested marrow-isolated adult multilineage-inducible (MIAMI) cells to induce neovascularization in a mouse model of critical hindlimb ischemia (CLI).
CLI was induced in the right hindlimb of Balb/C mice. One million MIAMI cells, normally grown at 3% O₂, were injected in the adductor muscle along the ischemic region. All animals (n = 11 per group) were immunosuppressed with cyclosporine daily for the entire period. Human foreskin fibroblast (HFF) cells and phosphate-buffered saline (PBS) were used as controls. Blood perfusion in the ischemic right and non-ischemic left hindlimbs was measured.
Compared with animals receiving HFF cells or PBS, MIAMI cells significantly improved blood perfusion, necrosis and inflammation in the ischemic limb. A fraction of injected MIAMI cells expressed CD31 and von Willebrand factor (vWF). MIAMI cells in vitro, under pro-angiogenic growth conditions, differentiated into endothelial-like cells and expressed endothelial markers such as CD31 and vWF, determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and CD31 and kinase insert domain receptor (KDR), determined by immunofluorescence. Moreover, MIAMI cells formed vascular endothelial-like tubules in the presence of matrigel. Bioplex immunoassay analysis showed increased secretion of angiogenic/anti-inflammatory factors by the MIAMI cells under 3% O₂ compared with 21% O₂, including monocyte chemoattractant protein-1 (MCP-1), fractalkine (Ftk), growth-related oncogene (GRO), vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8. Furthermore, transcripts for anti-inflammatory molecules stanniocalcin-1 (STC-1) and tumor necrosis factor-α-stimulated gene 6 (TSG-6) were up-regulated several fold.
MIAMI cells can be very useful for patients affected by CLI. MIAMI cells promote blood vessel formation and reduce inflammation and necrosis in ischemic tissue.
用干细胞治疗外周血管疾病（PVD）可能提供一种很有前途的策略。我们在严重的后肢缺血（CLI）小鼠模型中测试了骨髓分离的成年多谱系诱导（MIAMI）细胞，以诱导新生血管形成。
在 Balb/C 小鼠的右后肢诱导 CLI。将 100 万个 MIAMI 细胞（正常在 3%氧气下生长）注射到沿缺血区域的内收肌中。所有动物（每组 11 只）在整个期间每天接受环孢素免疫抑制。用人包皮成纤维细胞（HFF）和磷酸盐缓冲盐水（PBS）作为对照。测量缺血右侧和非缺血左侧后肢的血液灌注。
与接受 HFF 细胞或 PBS 的动物相比，MIAMI 细胞显著改善了缺血肢体的血液灌注、坏死和炎症。注射的 MIAMI 细胞中有一部分表达 CD31 和血管性血友病因子（vWF）。在促血管生成生长条件下，MIAMI 细胞在体外分化为内皮样细胞，并通过定量逆转录聚合酶链反应（qRT-PCR）表达内皮标志物如 CD31 和 vWF，通过免疫荧光表达 CD31 和激酶插入结构域受体（KDR）。此外，MIAMI 细胞在 Matrigel 存在的情况下形成血管内皮样小管。Bioplex 免疫分析显示，与 21%氧气相比，MIAMI 细胞在 3%氧气下分泌的血管生成/抗炎因子增加，包括单核细胞趋化蛋白-1（MCP-1）、 fractalkine（Ftk）、生长相关癌基因（GRO）、血管内皮生长因子（VEGF）、白细胞介素（IL）-6 和 IL-8。此外，抗炎分子 STC-1 和肿瘤坏死因子-α刺激基因 6（TSG-6）的转录物被上调了数倍。
MIAMI 细胞对 CLI 患者非常有用。MIAMI 细胞促进血管形成，减少缺血组织的炎症和坏死。
