一项新研究发现，一种蛋白质能够促进造血干细胞增殖并形成血液细胞，因此这种蛋白质有可能用来制作药剂，以用于恢复因放化疗而减少的白细胞和红细胞。
造血干细胞是指骨髓中的干细胞，具有自我复制能力，且可以分裂形成白细胞、红细胞和血小板等。但造血干细胞通常只有很少一部分缓慢分裂，大部分几乎都处于“冬眠状态”。人体因化疗和放疗导致血液细胞减少后，造血干细胞会开始分裂，但其机制一直没有弄清。
日本庆应义塾大学副教授中岛秀明等人在27日的美国《血液》月刊上发表论文说，他们在动物实验中发现，老鼠进行化疗和放疗后，骨髓中称为“TIMP3”的蛋白质增加。而在培养皿中，向采自老鼠骨髓的造血干细胞添加“TIMP3”蛋白质进行培养后，发现造血干细胞增殖活跃，数量相当于未添加时的1.5倍至2倍，血液细胞也随之增加。
研究人员还发现，如果使老鼠体内无法生产“TIMP3”蛋白质，则血液细胞减少难以恢复。而一旦“TIMP3”过剩，处于“冬眠”状态的造血干细胞就苏醒过来，开始分裂。
研究人员说，在进行化疗和放疗时，人体骨髓中的血液细胞会受到破坏，从而减少，容易出现感染和贫血等问题。如利用“TIMP3”蛋白质，就有望加快恢复因化疗和放疗而减少的血液细胞，除防止感染外，还可以减少输血量。
生物谷推荐原文出处：
Blood DOI 10.1182/blood-2010-01-266528.
TIMP-3 recruits quiescent hematopoietic stem cells into active cell cycle and expands multipotent progenitor pool
Hideaki Nakajima1,*, Miyuki Ito2, David S. Smookler3, Fumi Shibata4, Yumi Fukuchi1, Yoshihiro Morikawa5, Yuichi Ikeda4, Fumio Arai6, Toshio Suda6, Rama Khokha3 and Toshio Kitamura4
Regulating transition of hematopoietic stem cells (HSCs) between quiescent and cycling states is critical for maintaining homeostasis of blood cell production. The cycling states of HSCs are regulated by the extracellular factors such as cytokines and extracellular matrix, however, the molecular circuitry for such regulation remains elusive. Here we show that tissue inhibitor of metalloproteinase-3 (TIMP-3), an endogenous regulator of metalloproteinases, stimulates HSC proliferation by recruiting quiescent HSCs into the cell cycle. Myelosuppression induced TIMP-3 in the bone marrow prior to hematopoietic recovery. Interestingly, TIMP-3 enhanced proliferation of HSCs and promoted expansion of multipotent progenitors, which was achieved by stimulating cell-cycle entry of quiescent HSCs without compensating their long-term repopulating activity. Surprisingly, this effect did not require metalloproteinase inhibitory activity of TIMP-3, and was possibly mediated through a direct inhibition of angiopoietin-1 signaling, a critical mediator for HSC quiescence. Furthermore, BM recovery from myelosuppression was accelerated by overexpression of TIMP-3, and in turn, impaired in TIMP-3-deficient animals. These results suggest that TIMP-3 may act as a molecular cue in response to myelosuppression for recruiting dormant HSCs into active cell cycle, and may be clinically useful for facilitating hematopoietic recovery after chemotherapy or ex vivo expansion of HSCs.
