title: Cell and gene therapy using mesenchymal stem cells (MSCs).
abstract: Mesenchymal stem cells (MSCs) are considered to be a promising platform for cell and gene therapy for a variety of diseases. First, in the field of hematopoietic stem cell transplantation, there are two applications of MSCs: 1) the improvement of stem cell engrafting and the acceleration of hematopoietic reconstitution based on the hematopoiesis-supporting ability; and 2) the treatment of severe graft-versus-host disease (GVHD) based on the immunomodulatory ability. Regarding the immunosuppressive ability, we found that nitric oxide (NO) is involved in the MSC-mediated suppression of T cell proliferation. Second, tumor-bearing nude mice were injected with luciferase-expressing MSCs. An in vivo imaging analysis showed the significant accumulation of the MSCs at the site of tumors. The findings suggest that MSCs can be utilized to target metastatic tumors and to deliver anti-cancer molecules locally. As the third application, MSCs may be utilized as a cellular vehicle for protein-supplement gene therapy. When long-term transgene expression is needed, a therapeutic gene should be introduced with a minimal risk of insertional mutagenesis. To this end, site-specific integration into the AAVS1 locus on the chromosome 19 (19q13.4) by using the integration machinery of adeno-associated virus (AAV) would be particularly valuable. There will be wide-ranging applications of MSCs to frontier medical treatments in the near future.
authors.affiliation: Division of Hematology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sato
authors.forename: Iekuni
authors.initials: I
authors.lastname: Oh
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Uchibori
authors.forename: Yoko
authors.initials: Y
authors.lastname: Obara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.forename: Masashi
authors.initials: M
authors.lastname: Urabe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kume
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors; D006086:Graft vs Host Disease / Q000628:therapy*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009569:Nitric Oxide / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D007371:Interferon-gamma; D009569:Nitric Oxide; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase