title: Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo.
abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore "immunologically safe" for use in allogeneic clinical applications.
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Sang Young
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Jueun
authors.initials: J
authors.lastname: Ha
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Miyeon
authors.initials: M
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Soon-Jae
authors.initials: SJ
authors.lastname: Kwon
authors.affiliation: Research Institute for Future Medicine Stem Cell & Regenerative Medicine Center, Samsung Medical Center, Seoul 137-710, Republic of Korea.
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Wonil
authors.initials: W
authors.lastname: Oh
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea.
authors.forename: Yoon Sun
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-709, Republic of Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874, Republic of Korea. Electronic address: jhb@medi-post.co.kr.
authors.forename: Hong Bae
authors.initials: HB
authors.lastname: Jeon
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018952:Antigens, CD34; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Allogeneic; Human umbilical cord blood derived-mesenchymal stem cell (hUCB-MSC); Humanized NSG mouse; Low immunogenicity