日本研究人员在动物实验中使用脑梗塞治疗药物tPA，成功令实验鼠因血管闭塞坏死的肌肉再生。
来自东京大学医学研究所等机构的研究人员在新一期美国《血液》杂志上报告说，tPA是一种组织型纤溶酶原激活剂，摄入tPA可使体内的纤维蛋白溶酶增加。与此同时，源自骨髓的各种细胞聚集到坏死组织周围，其中一部分细胞能分泌促进组织再生的血管新生因子。
研究人员人为地使实验鼠脚部血管闭塞造成肌肉坏死，然后为其注射tPA。他们观察发现实验鼠肌肉再生，步行等运动功能也得到恢复。而且，tPA没有造成出血等副作用。
tPA具有溶血栓功效，通常用于治疗脑梗塞，在脑梗塞发作后短时间内注射有效。研究人员说，用tPA治疗肌肉坏死牵涉到的伦理和安全性问题较少，实用性较强。他们认为这种疗法也可用于心肌细胞和神经细胞的再生。
推荐原始出处：
Blood January 28, 2010; DOI 10.1182/blood-2009-08-236851.
Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration
Makiko Ohki1, Yuichi Ohki1, Makoto Ishihara1, Chiemi Nishida1, Yoshihiko Tashiro1, Haruyo Akiyama1, Hiromitsu Komiyama1, Leif R. Lund2, Atsumi Nitta3, Kiyofumi Yamada3, Zhenping Zhu4, Hideoki Ogawa5, Hideo Yagita6, Ko Okumura5, Hiromitsu Nakauchi1, Zena Werb7, Beate Heissig8 and Koichi Hattori1,*
1 Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; 2 Department of Cellular and Molecular Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark; 3 Department of Neuropsychopharmacology, Nagoya University Graduate School of Medicine, Nagoya, Japan; 4 ImClone Systems, NY; 5 Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan; 6 Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; 7 Department of Anatomy, University of California, San Francisco, California, United States; 8 Frontier Research Initiative, Institute of Medical Science at the University of Tokyo, Tokyo, Japan
Ischemia of the heart, brain and limbs is a leading cause of morbidity and mortality worldwide. Treatment with tissue type plasminogen activator (tPA) can dissolve blood clots and can ameliorate the clinical outcome in ischemic diseases. But the underlying mechanism by which tPA improves ischemic tissue regeneration is not well understood. Bone marrow (BM)-derived myeloid cells facilitate angiogenesis during tissue regeneration. Here we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin expands the myeloid cell pool and mobilizes CD45+CD11b+ pro-angiogenic, myeloid cells, a process dependent on vascular endothelial growth factor-A (VEGF-A) and Kit ligand signaling. tPA improves the incorporation of CD11b+ cells into ischemic tissues, and increases expression of neoangiogenesis-related genes including VEGF-A. Remarkably, transplantation of BM-derived tPA-mobilized CD11b+ cells and VEGFR-1+ cells, but not carrier-mobilized cells or CD11b- cells, accelerates neovascularization and ischemic tissue regeneration. Inhibition of VEGF-signaling suppresses tPA-induced neovascularization in a model of hindlimb ischemia. Thus, tPA mobilizes CD11b+ cells from the BM and increases systemic and local (cellular) VEGF-A, which can locally promote angiogenesis during ischemic recovery. tPA might be useful to induce therapeutic revascularization in the growing field of regenerative medicine.
