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Nature:减少骨髓脂肪细胞可提高造血能力

来源:科技日报 2009-06-24 14:14

科学家一直认为骨髓中的脂肪细胞只占用空间而没有其他不良影响,但美国科学家近日宣布,脂肪细胞会明显减慢骨髓中新的血细胞形成速度,因此,减少这些脂肪细胞可能有助于接受了骨髓移植手术的癌症病人更快地恢复,相关研究发表在最新一期出版的《自然》杂志上。

由美国哈佛医学院乔治·戴雷领导的研究团队发现,如果对老鼠进行基因改造,让其骨髓中不能制造脂肪细胞,那么,这些老鼠能够更有效地制造血细胞。研究人员同时发现,在实验室中,抑制脂肪细胞形成的化合物能够明显改进老鼠制造血细胞的能力。

人在出生时,骨髓中充满了制造血液的细胞,但随着年龄增长,脂肪细胞慢慢侵入骨髓,“鸠占鹊巢”,减慢了血细胞的产生。

戴雷和同事在老鼠身上进行了一系列实验,他们发现,在脂肪细胞相对较多的老鼠尾巴骨头中,只有25%的干细胞能够形成血液;而在身体其他部分的骨头中,75%的干细胞能够制造血液。

研究人员在老鼠身上使用了抑制脂肪细胞形成的化合物,或者对老鼠进行基因改造,让其不能形成脂肪细胞,研究发现,老鼠能够更快地长出骨髓,即使这些骨髓经过辐射已经被除去。这些老鼠能够更好地产生血祖细胞,这些血祖细胞对于骨髓移植手术后的病人快速恢复非常重要。(生物谷Bioon.com)

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Nature 10 June 2009 | doi:10.1038/nature08099

Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment

Olaia Naveiras1, Valentina Nardi1,4, Pamela L. Wenzel1,4, Peter V. Hauschka2, Frederic Fahey3 & George Q. Daley1

Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Division of Hematology, Brigham and Women's Hospital; Harvard Stem Cell Institute; Manton Center for Orphan Diseases; Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA

1 Departments of Orthopaedic Surgery and Oral and Developmental Biology, Harvard Medical School and School of Dental Medicine, Boston, Massachusetts, 02115, USA
2 Department of Radiology, Division of Nuclear Medicine/PET, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
3 These authors contributed equally to this work.
4 Correspondence to: George Q. Daley1 Correspondence and requests for materials should be addressed to G.Q.D.

Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow1, 2, 3. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia4. To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes5, and in mice treated with the peroxisome proliferator-activated receptor- inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis6, marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.

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