Aranguren Xabier L, McCue Jonathan D, Hendrickx Benoit, Zhu Xiao-Hong, Du Fei, Chen Eleanor, Pelacho Beatriz, Peñuelas Ivan, Abizanda Gloria, Uriz Maialen, Frommer Sarah A, Ross Jeffrey J, Schroeder Betsy A, Seaborn Meredith S, Adney Joshua R, Hagenbrock Julianna, Harris Nathan H, Zhang Yi, Zhang Xiaoliang, Nelson-Holte Molly H, Jiang Yuehua, Billiau An D, Chen Wei, Prósper Felipe, Verfaillie Catherine M, Luttun Aernout
Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium.
J Clin Invest. 2008 Feb;118(2):505-14. doi: 10.1172/JCI31153.
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.
尽管心血管研究取得了进展，但尚未找到治疗外周血管疾病的方法。我们在中度肢体缺血的小鼠中比较了小鼠和人类未分化的多能成年祖细胞（mMAPC-U和hMAPC-U）、小鼠MAPC衍生的血管祖细胞（mMAPC-VP）和未分选的小鼠骨髓细胞（mBMCs）的血管生成和组织再生潜力，这类似于人类患者的间歇性跛行。mMAPC-U通过直接和营养作用促进血管和骨骼肌生长，持久地恢复了血流和肌肉功能，并刺激了肌肉再生。这与mBMCs和mMAPC-VP形成对比，它们不影响肌肉再生，仅提供有限和短暂的改善。此外，mBMCs参与了下肢持续的炎症反应，这与肌肉功能的逐渐恶化有关。重要的是，mMAPC-U和hMAPC-U还纠正了严重肢体缺血中的血管和肌肉缺陷，这代表了人类的严重肢体缺血。因此，与BMCs或血管定向祖细胞不同，未分化的多能成年祖细胞具有持久修复外周血管疾病患者缺血损伤的潜力。
