美國杜克大學(xué)醫(yī)學(xué)中心科學(xué)家日前通過實驗確認(rèn),多效生長因子可促進(jìn)造血干細(xì)胞擴張和再生,。這項成果在再生醫(yī)學(xué)領(lǐng)域具有廣闊應(yīng)用前景,。
有關(guān)論文已發(fā)表在新一期英國《自然—醫(yī)學(xué)》(Nature Medicine)雜志上。研究人員在論文中表示,,對需要干細(xì)胞移植的患者而言,臍帶血是普遍的造血干細(xì)胞來源,,但臍帶血中的干細(xì)胞數(shù)量通常比較有限,,因此開發(fā)出能快速促進(jìn)臍帶血干細(xì)胞生長的方法就尤為重要。
研究人員將多效生長因子注入骨髓生長因受到輻射而被抑制的實驗鼠體內(nèi),,后者的骨髓干細(xì)胞生長速度與未注射多效生長因子的實驗鼠相比提高了10倍,。在實驗室培養(yǎng)皿中,多效生長因子還被確認(rèn)可促進(jìn)人類臍帶血干細(xì)胞的生長,。研究人員還證實,,多效生長因子不會導(dǎo)致實驗鼠出現(xiàn)癌變。
研究人員說,,這項成果將來有望使更廣泛的人群受益于臍帶血移植,,更重要的是,對正在接受化療或放療的患者而言,,利用多效生長因子進(jìn)行的治療或許具有加速患者血液和免疫系統(tǒng)恢復(fù)的潛力,。不過他們也表示,在利用這項成果進(jìn)行臨床治療前,,還需要進(jìn)行更多動物實驗,。
研究人員目前正在進(jìn)一步開展實驗,以驗證多效生長因子是否也對普通干細(xì)胞的生長和發(fā)展至關(guān)重要,。(生物谷Bioon.com)
生物谷推薦原文出處:
Nature Medicine DOI: doi:10.1038/nm.2119
Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells
Heather A Himburg,Garrett G Muramoto,Pamela Daher,Sarah K Meadows,J Lauren Russell,Phuong Doan,Jen-Tsan Chi,Alice B Salter,William E Lento,Tannishtha Reya,Nelson J Chao& John P Chute
Hematopoietic stem cell (HSC) self-renewal is regulated by both intrinsic and extrinsic signals. Although some of the pathways that regulate HSC self-renewal have been uncovered, it remains largely unknown whether these pathways can be triggered by deliverable growth factors to induce HSC growth or regeneration. Here we show that pleiotrophin, a neurite outgrowth factor with no known function in hematopoiesis, efficiently promotes HSC expansion in vitro and HSC regeneration in vivo. Treatment of mouse bone marrow HSCs with pleiotrophin caused a marked increase in long-term repopulating HSC numbers in culture, as measured in competitive repopulating assays. Treatment of human cord blood CD34+CDCD38?Lin? cells with pleiotrophin also substantially increased severe combined immunodeficient (SCID)-repopulating cell counts in culture, compared to input and cytokine-treated cultures. Systemic administration of pleiotrophin to irradiated mice caused a pronounced expansion of bone marrow stem and progenitor cells in vivo, indicating that pleiotrophin is a regenerative growth factor for HSCs. Mechanistically, pleiotrophin activated phosphoinositide 3-kinase (PI3K) signaling in HSCs; antagonism of PI3K or Notch signaling inhibited pleiotrophin-mediated expansion of HSCs in culture. We identify the secreted growth factor pleiotrophin as a new regulator of both HSC expansion and regeneration.