Multipotent adult progenitor cells sustain function of ischemic limbs in mice
Multipotent adult progenitor cells sustain function of ischemic limbs in mice
复制标题
DOI：
10.1172/jc131153
复制
发表时间：
2008-02-01
影响因子：
15.9
通讯作者：
Luttun, Aernout
中科院分区：
文献类型：
--
作者：
Aranguren, Xabier L.;McCue, Jonathan D.;Luttun, Aernout
尽管心血管研究取得了进展，但尚未找到治疗周围血管疾病的方法。我们比较了小鼠和人类未分化多能成体祖细胞（mMAPC-U和hMAPC-U）、小鼠MAPC衍生血管祖细胞（mMAPC-VP）和未选择的小鼠BM细胞（mBMC）在中度肢体缺血小鼠中的血管化和组织再生潜力，这让人想起人类患者的间歇性跛行。 mMAPC-U 通过对血管和骨骼肌生长的直接和营养贡献，持久地恢复血流和肌肉功能并刺激肌肉再生。这与 mBMC 和 mMAPC-VP 形成鲜明对比，mBMC 和 mMAPC-VP 不会影响肌肉再生，并且仅提供有限且短暂的改善。此外，mBMC 参与下肢持续的炎症反应，与肌肉功能的逐渐恶化相关。重要的是，mMAPC-U 和 hMAPC-U 还可以修复严重肢体缺血（人类严重肢体缺血的代表）中的血管和肌肉缺陷。因此，与 BMC 或血管定向祖细胞不同，未分化的多能成体祖细胞具有持久修复周围血管疾病患者缺血性损伤的潜力。
Despite progress in cardiovascular research, a cure for peripheral vascular disease has not been found. We compared the vascularization and tissue regeneration potential of murine and human undifferentiated multipotent adult progenitor cells (mMAPC-U and hMAPC-U), murine MAPC-derived vascular progenitors (mMAPC-VP), and unselected murine BM cells (mBMCs) in mice with moderate limb ischemia, reminiscent of intermittent claudication in human patients. mMAPC-U durably restored blood flow and muscle function and stimulated muscle regeneration, by direct and trophic contribution to vascular and skeletal muscle growth. This was in contrast to mBMCs and mMAPC-VP, which did not affect muscle regeneration and provided only limited and transient improvement. Moreover, mBMCs participated in a sustained inflammatory response in the lower limb, associated with progressive deterioration in muscle function. Importantly, mMAPC-U and hMAPC-U also remedied vascular and muscular deficiency in severe limb ischemia, representative of critical limb ischemia in humans. Thus, unlike BMCs or vascular-committed progenitors, undifferentiated multipotent adult progenitor cells offer the potential to durably repair ischemic damage in peripheral vascular disease patients.