title: Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer.
abstract: Recent research advances have established mesenchymal stem cells (MSCs) as a promising vehicle for therapeutic delivery. Their intrinsic tropism for brain injury and brain tumors, their lack of immunogenicity, and their ability to breach the blood-brain barrier make these cells an attractive potential treatment of brain disorders, including brain cancer. Despite these advantages, the efficiency of MSC homing to the brain has been limited in commonly used protocols, hindering the feasibility of such therapies. In the present study, we report a reproducible, comprehensive, cell culture-based approach to enhance human adipose-derived MSC (hAMSC) engraftment to brain tumors. We used micro- and nanotechnological tools to systematically model several steps in the putative homing process. By pre-exposing hAMSCs to glioma-conditioned media and the extracellular matrix proteins fibronectin and laminin, we achieved significant enhancements of the individual homing steps in vitro. This homing was confirmed in an in vivo rodent model of brain cancer. This comprehensive, cell-conditioning approach provides a novel method to enhance stem cell homing to gliomas and, potentially, other neurological disorders.
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Chris L
authors: CL
authors: Smith
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Kaisorn L
authors: KL
authors: Chaichana
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Young M
authors: YM
authors: Lee
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Benjamin
authors: B
authors: Lin
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Kevin M
authors: KM
authors: Stanko
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Thomas
authors: T
authors: O'Donnell
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Saksham
authors: S
authors: Gupta
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Sagar R
authors: SR
authors: Shah
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Joanne
authors: J
authors: Wang
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Olindi
authors: O
authors: Wijesekera
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Michael
authors: M
authors: Delannoy
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA aquinon2@jhmi.edu andre.levchenko@yale.edu.
authors: Andre
authors: A
authors: Levchenko
authors: Departments of Neurosurgery and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA aquinon2@jhmi.edu andre.levchenko@yale.edu.
authors: Alfredo
authors: A
authors: Quiñones-Hinojosa
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D064593:Heterografts; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D017077:Culture Media, Conditioned
keywords: Adipose; Bone marrow; Brain tumor; Glioblastoma; Homing; Mesenchymal stem cells
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