Adenoviral vector-mediated transfer of the Indian hedgehog gene modulates lymphomyelopoiesis in vivo
Adenoviral vector-mediated transfer of the Indian hedgehog gene modulates lymphomyelopoiesis in vivo
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DOI：
10.1634/stemcells.2007-0741
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发表时间：
2008-02-01
期刊：
影响因子：
5.2
通讯作者：
Niitsu, Yoshiro
中科院分区：
文献类型：
--
作者：
Kobune, Masayoshi;Kato, Junii;Niitsu, Yoshiro
印度刺猬（Ihh）在胚胎发育过程中的血管生成、血液发生和骨骺形成中起着重要作用。在本研究中，我们将携带模拟对照（Adv-control）或Ihh（Adv-Ihh）基因的腺病毒载体（Adv）注射到严重联合免疫缺陷（SCID）或BALB/c小鼠中，以评估Ihh对体内生后造血的调节作用。静脉注射Adv-Ihh后，在肝脏中检测到载体衍生的Ihh mRNA的表达。在对SCID小鼠给予Adv-Ihh后4周，我们观察到与Advcontrol给药小鼠相比，骨髓中每10（5）个单核细胞中的c-Kit+细胞和克隆原细胞数量增加。此外，给药后的Adv-Ihh的BALB/c小鼠，脾B220+IgM（低）-CD 23（int），CD 2（int）B淋巴细胞和CD 4 + T淋巴细胞的数量大幅增加。此外，胸腺双阴性（DN）2、DN 3、CD 8+未成熟单阳性和CD 4 +/CD 8-细胞的数量相对于接受对照Adv载体的小鼠中的数量显著升高。我们的结果表明，Ihh增强的信号可以调节体内骨髓造血过程中脾B淋巴细胞和胸腺T淋巴细胞的增殖和分化。因此，刺猬信号通路的调节可以提供一种治疗策略，以刺激体内淋巴骨髓生成。
Indian hedgehog (Ihh) plays an essential role in angiogenesis, hematogenesis, and epiphysis formation during embryogenesis. In the present study, we injected an adenoviral vector (Adv) carrying the mock-control (Adv-control) or Ihh (Adv-Ihh) gene into severe combined immunodeficiency (SCID) or BALB/c mice to evaluate the effects of Ihh on the regulation of postnatal hematopoiesis in vivo. After the i.v. injection of Adv-Ihh, the expression of vector-derived Ihh mRNA was detected in the liver. Four weeks after administration of Adv-Ihh to SCID mice, we observed an increase in the number of c-Kit+ cells and clonogenic cells per 10(5) mononuclear cells in the bone marrow compared with Advcontrol-administered mice. Moreover, after administration of Adv-Ihh to BALB/c mice, the number of splenic B220+IgM(low)-CD23(int)CD2(int) B lymphocytes and CD4+ T lymphocytes was strongly increased. Furthermore, the number of thymic double-negative (DN)2, DN3, CD8+ immature single-positive, and CD4+/CD8- cells was significantly elevated relative to the number in mice that received the control Adv vector. Our results suggest that enhanced signaling by Ihh can modulate the proliferation and differentiation of splenic B lymphocytes and thymic T lymphocytes during bone marrow hematopoiesis in vivo. Thus, modulation of the hedgehog signaling pathway may provide a therapeutic strategy to stimulate lymphomyelopoiesis in vivo.