Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area–supporting cells

Kobune, Masayoshi; Kawano, Yutaka; Ito, Yoshinori; Chiba, Hiroki; Nakamura, Kiminori; Tsuda, Hajime; Sasaki, Katsunori; Dehari, Hironari; Uchida, Hiroaki; Honmou, Osamu; Takahashi, Sho; Bizen, Akiko; Takimoto, Rishu; Matsunaga, Takuya; Kato, Junji; Kato, Kazunori; Houkin, Kiyohiro; Niitsu, Yoshiro; Hamada, Hirofumi

doi:10.1016/s0301-472x(03)00177-2

Cited by 96 publications

(83 citation statements)

References 39 publications

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“…Cultured rat MSCs were CD73 antigen-positive (Figure 1b), which had been reported as one of the typical mesenchymal surface antigens on human MSCs 22 Contamination by hematopoietic cells (CD45 or CD11b/c) were not detected in our MSCs culture (Figure 1c, e). We also examined the differentiation of rat MSCs into the classical mesenchymal lineages.…”

Section: Characterization Of Primary Rat Mscssupporting

confidence: 51%

“…Evaluation of the in vitro differentiation ability of rat primary MSCs or gene-modified MSCs into classical mesenchymal lineages was carried out as previously described 15,22 Briefly, MSCs were treated with either osteogenic differentiation medium supplemented with 80 mg/ml vitamin C phosphate (WAKO Pure Chemical Industries, Osaka, Japan), 10 mM sodium b-glycerophosphate (Calbiochem, San Diego, CA, USA), and 0.1 mM dexamethasone (Sigma-Aldrich Inc.), or with adipogenic differentiation medium supplemented with 0.5 mM hydrocortisone, 500 mM isobutylmethylxanthine, and 60 mM indomethacin. The differentiation medium was changed every 3 days until day 21.…”

Section: In Vitro Differentiation Of Mscsmentioning

confidence: 99%

“…Among bone marrow stem cells, much attention has been paid to mesenchymal stem cells (MSCs, also referred to as bone marrow stromal cells) because of their plasticity for differentiation into classical mesenchymal lineages, such as adipocytes, chondrocytes, and osteocytes, [15][16][17][18] and also neuronal lineages. [19][20][21][22] This neurogenic potential of MSCs was revealed under special culture conditions or following intracranial implantation. [23][24][25] Furthermore, it has been reported that MSCs can manifest multiple neural phenotypes even without neurogenic stimulation.…”

Section: Introductionmentioning

confidence: 99%

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Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

et al. 2004

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The prognosis of patients with malignant glioma is extremely poor, despite the extensive surgical treatment that they receive and recent improvements in adjuvant radio-and chemotherapy. In the present study, we propose the use of gene-modified mesenchymal stem cells (MSCs) as a new tool for gene therapy of malignant brain neoplasms. Primary MSCs isolated from Fischer 344 rats possessed excellent migratory ability and exerted inhibitory effects on the proliferation of 9L glioma cell in vitro. We also confirmed the migratory capacity of MSCs in vivo and showed that when they were inoculated into the contralateral hemisphere, they migrated towards 9L glioma cells through the corpus callosum. MSCs implanted directly into the tumor localized mainly at the border between the 9L tumor cells and normal brain parenchyma, and also infiltrated into the tumor bed. Intratumoral injection of MSCs caused significant inhibition of 9L tumor growth and increased the survival of 9L glioma-bearing rats. Gene-modification of MSCs by infection with an adenoviral vector encoding human interleukin-2 (IL-2) clearly augmented the antitumor effect and further prolonged the survival of tumor-bearing rats. Thus, gene therapy employing MSCs as a targeting vehicle would be promising as a new therapeutic approach for refractory brain tumor.

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Section: Characterization Of Primary Rat Mscssupporting

confidence: 51%

Section: In Vitro Differentiation Of Mscsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

et al. 2004

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“…23,28 Aliquots of cells were cultured in quadruplicate with the use of 35-mm tissue culture dishes in 1 mL MethoCult GF H4434V (Stem Cell Technologies, Vancouver, Canada). After 14 days of culture in a humidified environment at 37°C under 5% CO 2 , colonies consisting of 50 or more cells were scored under a microscope.…”

Section: Analysis Of Clonogenic Cellsmentioning

confidence: 99%

Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID–ß2m–/– repopulating cells.

Kobune

Ito

Kawano

et al. 2004

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“…MSCs can be isolated and expanded as plastic adherent cells having a flattened fibroblast-like morphology (Friedenstein, 1976;Woodbury et al, 2000) that are CD34 − , CD45 − , SH2 + , and SH3 + (Majumdar et al, 1998;Kobune et al, 2003). MSCs have been suggested to differentiate into osteoblasts, chondrocytes, adipocytes and hepatocytes (Prockop, 1997;Pittenger et al, 1999;Sanchez-Ramos et al, 2000;Krause et al, 2001;Kobune et al, 2003).…”

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confidence: 99%

I.v. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat

et al. 2005

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Abstract-I.v. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

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Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area–supporting cells

Cited by 96 publications

References 39 publications

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID–ß2m–/– repopulating cells.

I.v. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat

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