一項(xiàng)新研究發(fā)現(xiàn),，一種蛋白質(zhì)能夠促進(jìn)造血干細(xì)胞增殖并形成血液細(xì)胞,，因此這種蛋白質(zhì)有可能用來制作藥劑,，以用于恢復(fù)因放化療而減少的白細(xì)胞和紅細(xì)胞,。
造血干細(xì)胞是指骨髓中的干細(xì)胞,，具有自我復(fù)制能力,，且可以分裂形成白細(xì)胞,、紅細(xì)胞和血小板等。但造血干細(xì)胞通常只有很少一部分緩慢分裂,，大部分幾乎都處于“冬眠狀態(tài)”,。人體因化療和放療導(dǎo)致血液細(xì)胞減少后，造血干細(xì)胞會開始分裂,，但其機(jī)制一直沒有弄清,。
日本慶應(yīng)義塾大學(xué)副教授中島秀明等人在27日的美國《血液》月刊上發(fā)表論文說，他們在動物實(shí)驗(yàn)中發(fā)現(xiàn),，老鼠進(jìn)行化療和放療后,，骨髓中稱為“TIMP3”的蛋白質(zhì)增加。而在培養(yǎng)皿中,，向采自老鼠骨髓的造血干細(xì)胞添加“TIMP3”蛋白質(zhì)進(jìn)行培養(yǎng)后,，發(fā)現(xiàn)造血干細(xì)胞增殖活躍，數(shù)量相當(dāng)于未添加時的1.5倍至2倍,，血液細(xì)胞也隨之增加,。
研究人員還發(fā)現(xiàn)，如果使老鼠體內(nèi)無法生產(chǎn)“TIMP3”蛋白質(zhì),，則血液細(xì)胞減少難以恢復(fù),。而一旦“TIMP3”過剩，處于“冬眠”狀態(tài)的造血干細(xì)胞就蘇醒過來,，開始分裂,。
研究人員說，在進(jìn)行化療和放療時,，人體骨髓中的血液細(xì)胞會受到破壞,，從而減少,，容易出現(xiàn)感染和貧血等問題。如利用“TIMP3”蛋白質(zhì),，就有望加快恢復(fù)因化療和放療而減少的血液細(xì)胞,，除防止感染外，還可以減少輸血量,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
