Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain

Amit K Srivastava; Camille A Bulte; Irina Shats; Piotr Walczak; Jeff W M Bulte

doi:10.1016/j.expneurol.2015.10.008

Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain

Exp Neurol. 2016 Jan;275 Pt 1(0 1):154-61. doi: 10.1016/j.expneurol.2015.10.008. Epub 2015 Oct 26.

Authors

Amit K Srivastava¹, Camille A Bulte¹, Irina Shats¹, Piotr Walczak², Jeff W M Bulte³

Affiliations

¹ Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
³ Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Chemical & Biomolecular Engineering, The Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jwmbulte@mri.jhu.edu.

Abstract

Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebrally transplanted, either alone, or together with syngeneic MSCs in immunocompetent BALB/c mice (n=20) or immunodeficient Rag2(-/-) mice as survival control (n=8). No immunosuppressive drug was given to any animal. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that co-transplantation of MSCs significantly improved (p<0.05) engrafted GRP survival. No significant change in signal intensities was observed in immunodeficient Rag2(-/-) mice, with transplanted cells surviving in both the GRP only and the GRP+MSC group. In contrast, on day 21 post-transplantation, we observed a 94.2% decrease in BLI signal intensity in immunocompetent mice transplanted with GRPs alone versus 68.1% in immunocompetent mice co-transplanted with MSCs and GRPs (p<0.05). Immunohistochemical analysis demonstrated a lower number of infiltrating CD45, CD11b(+) and CD8(+) cells, reduced astrogliosis, and a higher number of FoxP3(+) cells at the site of transplantation for the immunocompetent mice receiving MSCs. The present study demonstrates that co-transplantation of MSCs can be used to create a microenvironment that is more conducive to the survival of allogeneic GRPs.

Keywords: Bioluminescence imaging; Cell survival; Co-transplantation; Glial-restricted precursor; Immunomodulation; Mesenchymal stem cell.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / cytology*
Cell Survival / physiology*
Mesenchymal Stem Cell Transplantation / methods*
Mice
Mice, Inbred BALB C
Mice, Transgenic
Neuroglia / cytology*

Abstract

Publication types

MeSH terms

Grants and funding