Open AccessAdenoviral Vector‐Mediated Transfer of the Indian Hedgehog Gene Modulates Lymphomyelopoiesis In Vivo
Author(s) -
Kobune Masayoshi,
Kato Junji,
Kawano Yutaka,
Sasaki Katsunori,
Uchida Hiroaki,
Takada Kohichi,
Takahashi Sho,
Takimoto Rishu,
Niitsu Yoshiro
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0741
Subject(s) - biology , indian hedgehog , cd8 , hedgehog , endocrinology , in vivo , haematopoiesis , medicine , bone marrow , stem cell , immunology , cancer research , microbiology and biotechnology , signal transduction , immune system
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 lhh 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 Adv‐control‐administered mice. Moreover, after administration of Adv‐Ihh to BALB/c mice, the number of splenic B220+IgM low CD23 int CD21 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. Disclosure of potential conflicts of interest is found at the end of this article.