Impurity of stem cell graft by murine embryonic fibroblasts - implications for cell-based therapy of the central nervous system

Marek Molcanyi; Narges Zare Mehrjardi; Ute Schäfer; Nadia Nabil Haj-Yasein; Michael Brockmann; Marina Penner; Peter Riess; Clemens Reinshagen; Bernhard Rieger; Tobias Hannes; Jürgen Hescheler; Bert Bosche

doi:10.3389/fncel.2014.00257

Impurity of stem cell graft by murine embryonic fibroblasts - implications for cell-based therapy of the central nervous system

Front Cell Neurosci. 2014 Sep 5:8:257. doi: 10.3389/fncel.2014.00257. eCollection 2014.

Authors

Affiliations

¹ Institute of Neurophysiology, Medical Faculty, University of Cologne , Cologne , Germany ; Clinic of Neurosurgery, Medical Faculty, University of Cologne , Cologne , Germany.
² Institute of Neurophysiology, Medical Faculty, University of Cologne , Cologne , Germany.
³ Research Unit for Experimental Neurotraumatology, Medical University of Graz , Graz , Austria.
⁴ Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo , Oslo , Norway.
⁵ Department of Pathology, Kliniken der Stadt Köln, Cologne-Merheim Hospital, University of Witten/Herdecke , Cologne , Germany.
⁶ Clinic of Neurosurgery, Medical Faculty, University of Cologne , Cologne , Germany.
⁷ Department of Traumatology and Orthopedics, HELIOS Klinik Bad Berleburg , Bad Berleburg , Germany.
⁸ Molecular Neurotherapy and Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA ; Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
⁹ Institute of Neurophysiology, Medical Faculty, University of Cologne , Cologne , Germany ; Department of Pediatric Cardiology, Heart Center Cologne, Medical Faculty, University Hospital of Cologne , Cologne , Germany.
¹⁰ Division of Neurosurgery, St Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Department of Surgery, University of Toronto , Toronto, ON , Canada ; Department of Neurology, University Hospital of Essen, University of Duisburg-Essen , Essen , Germany.

Abstract

Stem cells have been demonstrated to possess a therapeutic potential in experimental models of various central nervous system disorders, including stroke. The types of implanted cells appear to play a crucial role. Previously, groups of the stem cell network NRW implemented a feeder-based cell line within the scope of their projects, examining the implantation of stem cells after ischemic stroke and traumatic brain injury. Retrospective evaluation indicated the presence of spindle-shaped cells in several grafts implanted in injured animals, which indicated potential contamination by co-cultured feeder cells (murine embryonic fibroblasts - MEFs). Because feeder-based cell lines have been previously exposed to a justified criticism with regard to contamination by animal glycans, we aimed to evaluate the effects of stem cell/MEF co-transplantation. MEFs accounted for 5.3 ± 2.8% of all cells in the primary FACS-evaluated co-culture. Depending on the culture conditions and subsequent purification procedure, the MEF-fraction ranged from 0.9 to 9.9% of the cell suspensions in vitro. MEF survival and related formation of extracellular substances in vivo were observed after implantation into the uninjured rat brain. Impurity of the stem cell graft by MEFs interferes with translational strategies, which represents a threat to the potential recipient and may affect the graft microenvironment. The implications of these findings are critically discussed.

Keywords: brain injury; cell graft contamination; feeder-based cell line; murine embryonic fibroblasts; stem cell transplantation; stroke.