Adenoviral Vector-Mediated Transfer of the Indian Hedgehog Gene Modulates Lymphomyelopoiesis In Vivo

¹ Fourth Dept of Internal Medicine, Sapporo Medical University School of Medicine, Dept. of Molecular Medicine, Sapporo Medical University School of Medicine
² Fourth Dept of Internal Medicine, Sapporo Medical University School of Medicine
³ Core Facility for Therapeutic Vectors, Institute of Medical Science, the University of Tokyo
⁴ Dept. of Surgery and Bioengineering, Institute of Medical Science, the University of Tokyo

^* To whom correspondence should be addressed. E-mail: mkobune{at}sapmed.ac.jp.

	Abstract

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 gene (Adv-Ihh) into SCID or BALB/c mice to evaluate the effects of lhh on the regulation of postnatal hematopoiesis in vivo. After the intravenous 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/10⁵ mononuclear cells in the bone marrow as compared with adv-control administrated mice. Moreover, after administration of Adv-Ihh to BALB/c mice, the number of splenic B220+IgM^lowCD23^intCD21^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 BM hematopoiesis in vivo. Thus, modulation of the Hh signaling pathway may provide a therapeutic strategy to stimulate lymphomyelopoiesis in vivo.