美国杜克大学医学中心科学家日前通过实验确认,多效生长因子可促进造血干细胞扩张和再生。这项成果在再生医学领域具有广阔应用前景。
有关论文已发表在新一期英国《自然—医学》(Nature Medicine)杂志上。研究人员在论文中表示,对需要干细胞移植的患者而言,脐带血是普遍的造血干细胞来源,但脐带血中的干细胞数量通常比较有限,因此开发出能快速促进脐带血干细胞生长的方法就尤为重要。
研究人员将多效生长因子注入骨髓生长因受到辐射而被抑制的实验鼠体内,后者的骨髓干细胞生长速度与未注射多效生长因子的实验鼠相比提高了10倍。在实验室培养皿中,多效生长因子还被确认可促进人类脐带血干细胞的生长。研究人员还证实,多效生长因子不会导致实验鼠出现癌变。
研究人员说,这项成果将来有望使更广泛的人群受益于脐带血移植,更重要的是,对正在接受化疗或放疗的患者而言,利用多效生长因子进行的治疗或许具有加速患者血液和免疫系统恢复的潜力。不过他们也表示,在利用这项成果进行临床治疗前,还需要进行更多动物实验。
研究人员目前正在进一步开展实验,以验证多效生长因子是否也对普通干细胞的生长和发展至关重要。(生物谷Bioon.com)
生物谷推荐原文出处:
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.