OBJECT: Authors of previous studies have reported that adult transplanted neural progenitor cells (NPCs) are suitable for brain cell replacement or gene delivery. In this study, the authors evaluated survival and integration of adult rat-derived NPCs after transplantation and explored the potential impact on transplant survival of various mechanical and biological factors of clinical importance. METHODS: Adult female Fischer 344 rats were used both as a source and recipient of transplanted NPCs. Both 9L and RG2 rat glioma cells were used to generate in vivo brain tumor models. On the 5th day after tumor implantation, NPCs expressing green fluorescent protein (GFP) were administered either intravenously (3.5 x 10(7) cells) or by stereotactic injection (1 x 10(4)-1 x 10(6) cells) into normal or tumor-bearing brain. The authors evaluated the effect of delivery method (sharp compared with blunt needles, normal compared with zero-volume needles, phosphate-buffered saline compared with medium as vehicle), delivery sites (intravenous compared with intratumoral compared with intraparenchymal), and pretreatment with an immunosuppressive agent (cyclosporin) or brain irradiation (20-40 Gy) on survival and integration of transplanted NPCs. RESULTS: Very few cells survived when less than 10(5) cells were transplanted. When 10(5) cells or more were transplanted, only previously administered brain irradiation significantly affected survival and integration of NPCs. Although GFP-containing NPCs could be readily detected 1 day after injection, few cells survived 4 days to 1 week unless preceded by whole-brain radiation (20 or 40 Gy in a single fraction), which increased the number of GFP-containing NPCs within the tissue more than fivefold. CONCLUSIONS: The authors' findings indicate that most NPCs, including those from a syngeneic autologous source, do not survive at the site of implantation, but that brain irradiation can facilitate subsequent survival in both normal and tumor-bearing brain. An understanding of the mechanisms of this effect could lead to improved survival and clinical utility of transplanted NPCs.
OBJECT: Authors of previous studies have reported that adult transplanted neural progenitor cells (NPCs) are suitable for brain cell replacement or gene delivery. In this study, the authors evaluated survival and integration of adult rat-derived NPCs after transplantation and explored the potential impact on transplant survival of various mechanical and biological factors of clinical importance. METHODS: Adult female Fischer 344 rats were used both as a source and recipient of transplanted NPCs. Both 9L and RG2 ratglioma cells were used to generate in vivo brain tumor models. On the 5th day after tumor implantation, NPCs expressing green fluorescent protein (GFP) were administered either intravenously (3.5 x 10(7) cells) or by stereotactic injection (1 x 10(4)-1 x 10(6) cells) into normal or tumor-bearing brain. The authors evaluated the effect of delivery method (sharp compared with blunt needles, normal compared with zero-volume needles, phosphate-buffered saline compared with medium as vehicle), delivery sites (intravenous compared with intratumoral compared with intraparenchymal), and pretreatment with an immunosuppressive agent (cyclosporin) or brain irradiation (20-40 Gy) on survival and integration of transplanted NPCs. RESULTS: Very few cells survived when less than 10(5) cells were transplanted. When 10(5) cells or more were transplanted, only previously administered brain irradiation significantly affected survival and integration of NPCs. Although GFP-containing NPCs could be readily detected 1 day after injection, few cells survived 4 days to 1 week unless preceded by whole-brain radiation (20 or 40 Gy in a single fraction), which increased the number of GFP-containing NPCs within the tissue more than fivefold. CONCLUSIONS: The authors' findings indicate that most NPCs, including those from a syngeneic autologous source, do not survive at the site of implantation, but that brain irradiation can facilitate subsequent survival in both normal and tumor-bearing brain. An understanding of the mechanisms of this effect could lead to improved survival and clinical utility of transplanted NPCs.
Authors: Oliver B Betz; Volker M Betz; Christian Schröder; Rainer Penzkofer; Michael Göttlinger; Susanne Mayer-Wagner; Peter Augat; Volkmar Jansson; Peter E Müller Journal: BMC Biotechnol Date: 2013-08-08 Impact factor: 2.563