title: Bone marrow-derived stem cell therapy for metastatic brain cancers.
abstract: We propose that stem cell therapy may be a potent treatment for metastatic melanoma in the brain. Here we discuss the key role of a leaky blood-brain barrier (BBB) that accompanies the development of brain metastases. We review the need to characterize the immunological and inflammatory responses associated with tumor-derived BBB damage in order to reveal the contribution of this brain pathological alteration to the formation and growth of brain metastatic cancers. Next, we discuss the potential repair of the BBB and attenuation of brain metastasis through transplantation of bone marrow-derived mesenchymal stem cells with the endothelial progenitor cell phenotype. In particular, we review the need for evaluation of the efficacy of stem cell therapy in repairing a disrupted BBB in an effort to reduce neuroinflammation, eventually attenuating brain metastatic cancers. The demonstration of BBB repair through augmented angiogenesis and vasculogenesis will be critical to establishing the potential of stem cell therapy for the treatment/prevention of metastatic brain tumors. The overarching hypothesis we advanced here is that BBB breakdown is closely associated with brain metastatic cancers of melanoma, exacerbating the inflammatory response of the brain during metastasis, and ultimately worsening the outcome of metastatic brain cancers. Abrogating this leaky BBB-mediated inflammation via stem cell therapy represents a paradigm-shifting approach to treating brain cancer. This review article discusses the pros and cons of cell therapy for melanoma brain metastases.
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Naoki
authors.initials: N
authors.lastname: Tajiri
authors.forename: Meaghan
authors.initials: M
authors.lastname: Staples
authors.forename: Stephanny
authors.initials: S
authors.lastname: Reyes
authors.forename: Diego
authors.initials: D
authors.lastname: Lozano
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Freeman
authors.forename: Harry
authors.initials: H
authors.lastname: van Loveren
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D001932:Brain Neoplasms / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D035683:MicroRNAs / Q000378:metabolism
chemical_list: D016207:Cytokines; D035683:MicroRNAs