In vivo tracking of superparamagnetic iron oxide nanoparticle–labeled mesenchymal stem cell tropism to malignant gliomas using magnetic resonance imaging

Wu, Xing; Hu, Jin; Zhou, Liangfu; Mao, Ying; Yang, Baofeng; Gao, Liang; Xie, Rong; Xu, Feng; Zhang, Dong; Liu, Jun; Zhu, Jiaan

doi:10.3171/jns/2008/108/2/0320

Cited by 101 publications

(106 citation statements)

References 46 publications

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“…Specific migration of MSCs in the brain is well documented for lesion sites in the brain, 39,40 as well as in gliomas. [41][42][43] However, tracking MSCs in normal brains shows a variety of engraftment sites, ranging from the cerebellum to the forebrain. 44,45 Sites in which active neurogenesis occurs in adulthood, such as the hippocampus, subventricular zone and olfactory bulb, are often included in these preferred engraftment sites.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

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Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (10 5 cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant-submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

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“…Previously, it has been suggested that mesenchymal stem cells (MSCs) may represent an alternative source of therapeutic stem cells (21,22). In experimental brain glioma models, intracranially implanted or intravenously injected MSCs can migrate away from the injection site toward tumor beds (23)(24)(25)(26)(27). Additionally, gene modification of MSCs with therapeutic cytokines clearly prolongs the survival of tumorbearing animals (23,25,28,29).…”

Section: Introductionmentioning

confidence: 99%

Chemokines mediate mesenchymal stem cell migration toward gliomas in vitro

Shi²,

Yu³

et al. 2010

Oncol Rep

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Abstract. Previous studies have demonstrated the tremendous tropism of mesenchymal stem cells (MSCs) for malignant gliomas, making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells. However, the mechanisms underlying the tropism of MSCs for gliomas remain poorly defined. It has been suggested that malignant gliomas secrete a variety of chemokines, including macrophage chemoattractant protein-1 (MCP-1) and stromal cell-derived factor-1· (SDF-1·). We isolated and cultured MSCs from rat bone marrow and found that these cells express CCR2 and CXCR4, the respective receptors for MCP-1 and SDF-1·. In vitro analysis revealed that MCP-1 and SDF-1· induce the migration of MSCs. Futhermore, neutralization data suggest that MCP-1 and SDF-1· play a role in the mediation of MSC migration toward gliomas. These results highlight the potential of these cells as a tumor targeting strategy for glioma gene therapy. IntroductionMalignant gliomas are the most prevalent type of primary brain tumor. Despite extensive surgical excision and adjuvant radio-and chemotherapy, the prognoses of patients with malignant gliomas, such as glioblastoma multiforme (GBM) or anaplastic astrocytoma, remain extremely poor (1-3). The median survival is 1 year or less for patients diagnosed with GBM and ~3 years for those diagnosed with anaplastic astrocytoma (4). This treatment resistance arises, in part, from tumor infiltration of and invasion into the surrounding brain architecture. Surgical tumor resection is almost always followed by regrowth of tumor cells residing in adjacent regions of normal brain tissue because it is impossible to eliminate successfully all tumor cells using current technologies (5-7). Single tumor cells deeply infiltrate the surrounding tissue, and are thought to be responsible for tumor relapse. New therapies should target these single tumor cells, especially those that have escaped the main tumor mass (8-10).Neural stem cells (NSCs) possess extensive tropism for experimental gliomas when administered intracranially (11,12). This characteristic of NSCs has been exploited as a tumor targeting strategy for glioma gene therapy (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Unfortunately, the acquisition of sufficient therapeutic NSCs is challenging technically, and their practical application is problematic due to ethical concerns and immunological rejection. Previously, it has been suggested that mesenchymal stem cells (MSCs) may represent an alternative source of therapeutic stem cells (21,22). In experimental brain glioma models, intracranially implanted or intravenously injected MSCs can migrate away from the injection site toward tumor beds (23-27). Additionally, gene modification of MSCs with therapeutic cytokines clearly prolongs the survival of tumorbearing animals (23,25,28,29).A better understanding of the molecular events that govern MSC homing is necessary for the development of a clinicallyapplicable tumor targeting strategy for glioma gene therapy. Certain chemokines and gro...

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“…MRI and magnetic resonance spectroscopy are common imaging modalities for in vivo stem cell tracking in both preclinical and clinical settings (Hoehn, Kustermann et al 2002;Modo, Cash et al 2002;van den Bos, Wagner et al 2003;Kustermann, Roell et al 2005;Crowder, Brant et al 2006;Jansen, Shamblott et al 2006;Au, Lam et al 2007;Hsiao, Tai et al 2007;Magnitsky, Walton et al 2007;Partlow, Chen et al 2007;Politi, Bacigaluppi et al 2007;Suzuki, Cunningham et al 2007;Dash, Chan et al 2008;Himmelreich and Hoehn 2008;Kim and Song 2008;Terrovitis, Stuber et al 2008;Wu, Hu et al 2008;Kedzioreik, Ouwerkerk et al 2009;Kim, Huh et al 2009;Lythgoe 2009;Reekmans, Tambuyzer et al 2009;Solanky, Chung et al 2010;Tseng, Shih et al 2010;Chien, Hsiao et al 2011). Extraordinary three dimensional and anatomic resolution and high safety profile are the main advantages.…”

Section: Mrimentioning

confidence: 99%

Clinical Stem Cell Imaging and In vivo Tracking

Mirpour¹,

Gholamrezanezhad²

2011

Stem Cells in Clinic and Research

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In vivo tracking of superparamagnetic iron oxide nanoparticle–labeled mesenchymal stem cell tropism to malignant gliomas using magnetic resonance imaging

Abstract: This study demonstrated that systemically transplanted MSCs migrate toward gliomas with high specificity in a temporal-spatial pattern, which can be tracked using MR imaging.

Cited by 101 publications

References 46 publications

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Chemokines mediate mesenchymal stem cell migration toward gliomas in vitro

Clinical Stem Cell Imaging and In vivo Tracking

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