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THE STEM CELL NICHE

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

^aFourth Department of Internal Medicine and
^bDepartment of Molecular Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan;
^cCore Facility for Therapeutic Vectors and
^dDepartment of Surgery and Bioengineering, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Key Words. Hedgehog • Adenovirus • Lymphocyte • Hematopoiesis • Spleen • Thymus

Correspondence: Masayoshi Kobune, M.D., Ph.D., Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Chuo-ku, South-1, West-16 Sapporo, Hokkaido 060-8556, Japan. Telephone: 81-11-611-2111, ext. 3254; Fax: 81-11-612-2136; e-mail: mkobune{at}sapmed.ac.jp

Received September 4, 2007; accepted for publication October 19, 2007.
First published online in STEM CELLS EXPRESS   October 25, 2007.



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 10⁵ 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^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 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.