Beckman Institute for Advanced Science and Technology, Urbana, IL.
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL.
Theranostics. 2017 Sep 5;7(16):3876-3888. doi: 10.7150/thno.19547. eCollection 2017.
Peripheral arterial disease (PAD) is a debilitating complication of diabetes mellitus (DM) that leads to thousands of injuries, amputations, and deaths each year. The use of mesenchymal stem cells (MSCs) as a regenerative therapy holds the promise of regrowing injured vasculature, helping DM patients live healthier and longer lives. We report the use of muscle-derived MSCs to treat surgically-induced hindlimb ischemia in a mouse model of type 1 diabetes (DM-1). We serially evaluate several facets of the recovery process, including -integrin expression (a marker of angiogenesis), blood perfusion, and muscle function. We also perform microarray transcriptomics experiments to characterize the gene expression states of the MSC-treated is- chemic tissues, and compare the results with those of non-ischemic tissues, as well as ischemic tissues from a saline-treated control group. The results show a multifaceted impact of mMSCs on hindlimb ischemia. We determined that the angiogenic activity one week after mMSC treatment was enhanced by approximately 80% relative to the saline group, which resulted in relative increases in blood perfusion and muscle strength of approximately 42% and 1.7-fold, respectively. At the transcriptomics level, we found that several classes of genes were affected by mMSC treatment. The mMSCs appeared to enhance both pro-angiogenic and metabolic genes, while suppressing anti-angiogenic genes and certain genes involved in the inflammatory response. All told, mMSC treatment appears to exert far-reaching effects on the microenvironment of ischemic tissue, enabling faster and more complete recovery from vascular occlusion.
外周动脉疾病 (PAD) 是糖尿病 (DM) 的一种使人虚弱的并发症，每年导致数千例损伤、截肢和死亡。间充质干细胞 (MSCs) 的应用作为一种再生疗法有望再生受损的脉管系统，帮助 DM 患者更健康、更长寿地生活。我们报告了使用肌肉源性 MSCs 治疗 1 型糖尿病 (DM-1) 小鼠模型中的手术诱导的后肢缺血。我们连续评估了恢复过程的几个方面，包括 -整合素表达（血管生成的标志物）、血液灌注和肌肉功能。我们还进行了微阵列转录组学实验，以表征 MSC 处理的缺血组织的基因表达状态，并将结果与非缺血组织以及来自盐水处理对照组的缺血组织进行比较。结果表明 mMSCs 对后肢缺血有多种影响。我们确定，与盐水组相比，mMSC 治疗后一周的血管生成活性增强了约 80%，导致血液灌注和肌肉强度分别相对增加约 42%和 1.7 倍。在转录组学水平上，我们发现几类基因受到 mMSC 治疗的影响。mMSCs 似乎增强了促血管生成和代谢基因，同时抑制了抗血管生成基因和某些参与炎症反应的基因。总的来说，mMSC 治疗似乎对缺血组织的微环境产生了深远的影响，使血管闭塞更快、更完全地恢复。
