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糖尿病患者脂肪来源基质细胞(ASCs)的血管新生潜力。

Neovascular potential of adipose-derived stromal cells (ASCs) from diabetic patients.

机构信息

Department of Plastic and Reconstructive Surgery, Korea University Guro Hospital, Guro-gu, Seoul, Korea.

出版信息

Wound Repair Regen. 2012 Mar-Apr;20(2):243-52. doi: 10.1111/j.1524-475X.2012.00765.x. Epub 2012 Feb 14.

Abstract

We explored the vascular biology of adipose-derived stromal cells (ASCs) from diabetic patients and applied these cells to a murine ischemic flap model to assess the comparative angiogenic potentials between normal and diabetic human ASCs. ASCs were obtained from diabetic patients (n = 5) and controls (n = 5). Secretion and expression of angiogenic cytokines were measured under normoxic and hypoxic condition in vitro. Conditioned media harvested from ASC cultures were assessed for their ability to stimulate human umbilical vein endothelial cell proliferation and tubulization. The control and diabetic ASCs were injected into the murine ischemic flaps, and the surviving area was measured. Diabetic adipose-derived stromal cells showed a lower level of vascular endothelial growth factor expression and cell proliferation rates than the control cells (p < 0.05). However, vascular endothelial growth factor, hepatocyte growth factor secretion, tubulogenesis, and cell proliferation in diabetic conditioned media were increased in response to hypoxic stimuli (p < 0.05), and it was similar to those of control cells. In an animal study, diabetic and normal ASCs significantly increased flap survival (p < 0.05); however, the functional difference was not found between the two groups. Diabetic ASCs were impaired in their ability to produce vascular endothelial growth factors and to induce cellular proliferation under hypoxic conditions. However, diabetic ASCs showed similar flap salvaging effect compared with controls. These findings may be important in the context of future study of autologous cell-based therapy in diabetic patients.

摘要

我们研究了糖尿病患者脂肪来源基质细胞 (ASCs) 的血管生物学,并将这些细胞应用于小鼠缺血皮瓣模型,以评估正常和糖尿病患者来源的 ASC 的比较血管生成潜力。从糖尿病患者(n=5)和对照者(n=5)中获得 ASC。在体外常氧和低氧条件下测量血管生成细胞因子的分泌和表达。评估 ASC 培养物中收获的条件培养基刺激人脐静脉内皮细胞增殖和小管形成的能力。将对照和糖尿病 ASC 注射到小鼠缺血皮瓣中,并测量存活面积。与对照细胞相比,糖尿病脂肪来源基质细胞的血管内皮生长因子表达和细胞增殖率较低(p<0.05)。然而,血管内皮生长因子、肝细胞生长因子分泌、小管形成和糖尿病条件培养基中的细胞增殖在低氧刺激下增加(p<0.05),与对照细胞相似。在动物研究中,糖尿病和正常 ASC 显著增加皮瓣存活(p<0.05);然而,两组之间没有发现功能差异。糖尿病 ASC 在产生血管内皮生长因子和在低氧条件下诱导细胞增殖的能力受损。然而,与对照组相比,糖尿病 ASC 显示出相似的皮瓣挽救效果。这些发现可能对未来研究糖尿病患者自体细胞治疗具有重要意义。

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