Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury

Timo Schomann; Juvita D. Iljas; Ivo Que; Yuedan Li; Ernst Suidgeest; Luis J. Cruz; Johan H.M. Frijns; Alan Chan; Clemens M.W.G. Löwik; Margriet A. Huisman; Laura Mezzanotte

doi:10.1007/s00441-020-03173-1

Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury

Timo Schomann
, Juvita D. Iljas
, Ivo Que
, Yuedan Li
, Ernst Suidgeest
, Luis J. Cruz
, Johan H.M. Frijns
, Alan Chan
, Clemens M.W.G. Löwik
, Margriet A. Huisman
, Laura Mezzanotte^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

4 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) is a devastating event for which current therapies are limited. Stem cell transplantation may lead to recovery of function via different mechanisms, such as cell replacement through differentiation, stimulation of angiogenesis and support to the microenvironment. Adult hair follicle bulge-derived stem cells (HFBSCs) possess neuronal differentiation capacity, are easy to harvest and are relatively immune-privileged, which makes them potential candidates for autologous stem cell-based therapy. In this study, we apply in vivo multimodal, optical and magnetic resonance imaging techniques to investigate the behavior of mouse HFBSCs in a mouse model of TBI. HFBSCs expressed Luc2 and copGFP and were examined for their differentiation capacity in vitro. Subsequently, transduced HFBSCs, preloaded with ferumoxytol, were transplanted next to the TBI lesion (cortical region) in nude mice, 2 days after injury. Brains were fixed for immunohistochemistry 58 days after transplantation. Luc2- and copGFP-expressing, ferumoxytol-loaded HFBSCs showed adequate neuronal differentiation potential in vitro. Bioluminescence of the lesioned brain revealed survival of HFBSCs and magnetic resonance imaging identified their localization in the area of transplantation. Immunohistochemistry showed that transplanted cells stained for nestin and neurofilament protein (NF-Pan). Cells also expressed laminin and fibronectin but extracellular matrix masses were not detected. After 58 days, ferumoxytol could be detected in HFBSCs in brain tissue sections. These results show that HFBSCs are able to survive after brain transplantation and suggest that cells may undergo differentiation towards a neuronal cell lineage, which supports their potential use for cell-based therapy for TBI.

Original language	English
Pages (from-to)	55-69
Number of pages	15
Journal	Cell and Tissue Research
Volume	381
Issue number	1
DOIs	https://doi.org/10.1007/s00441-020-03173-1
Publication status	Published - 1 Jul 2020

Bibliographical note

Funding Information:
The authors acknowledge Carola van der Ploeg for technical assistance. We greatly acknowledge Louise van der Weerd (Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands) for support with analysis and interpretation of MRI data.

Funding Information:
This work was supported by the FP7 European Union Marie Curie IAPP Program, BRAINPATH, under grant number 612360, the project grant H2020-MSCA-RISE PRISAR grant number 644373 and by a grant from MED-EL (Innsbruck, Austria) grant number FK0151/MEDELI001.This project is financially supported by grants from Stichting Het Heinsius-Houbolt Fonds, the Netherlands. Timo Schomann received funding from MED-EL (Innsbruck, Austria). Acknowledgments

Publisher Copyright:
© 2020, The Author(s).

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10.1007/s00441-020-03173-1

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@article{ddefd96fd52a47498e857c05f8ef031e,

title = "Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury",

abstract = "Traumatic brain injury (TBI) is a devastating event for which current therapies are limited. Stem cell transplantation may lead to recovery of function via different mechanisms, such as cell replacement through differentiation, stimulation of angiogenesis and support to the microenvironment. Adult hair follicle bulge-derived stem cells (HFBSCs) possess neuronal differentiation capacity, are easy to harvest and are relatively immune-privileged, which makes them potential candidates for autologous stem cell-based therapy. In this study, we apply in vivo multimodal, optical and magnetic resonance imaging techniques to investigate the behavior of mouse HFBSCs in a mouse model of TBI. HFBSCs expressed Luc2 and copGFP and were examined for their differentiation capacity in vitro. Subsequently, transduced HFBSCs, preloaded with ferumoxytol, were transplanted next to the TBI lesion (cortical region) in nude mice, 2 days after injury. Brains were fixed for immunohistochemistry 58 days after transplantation. Luc2- and copGFP-expressing, ferumoxytol-loaded HFBSCs showed adequate neuronal differentiation potential in vitro. Bioluminescence of the lesioned brain revealed survival of HFBSCs and magnetic resonance imaging identified their localization in the area of transplantation. Immunohistochemistry showed that transplanted cells stained for nestin and neurofilament protein (NF-Pan). Cells also expressed laminin and fibronectin but extracellular matrix masses were not detected. After 58 days, ferumoxytol could be detected in HFBSCs in brain tissue sections. These results show that HFBSCs are able to survive after brain transplantation and suggest that cells may undergo differentiation towards a neuronal cell lineage, which supports their potential use for cell-based therapy for TBI.",

author = "Timo Schomann and Iljas, \{Juvita D.\} and Ivo Que and Yuedan Li and Ernst Suidgeest and Cruz, \{Luis J.\} and Frijns, \{Johan H.M.\} and Alan Chan and L{\"o}wik, \{Clemens M.W.G.\} and Huisman, \{Margriet A.\} and Laura Mezzanotte",

note = "Funding Information: The authors acknowledge Carola van der Ploeg for technical assistance. We greatly acknowledge Louise van der Weerd (Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands) for support with analysis and interpretation of MRI data. Funding Information: This work was supported by the FP7 European Union Marie Curie IAPP Program, BRAINPATH, under grant number 612360, the project grant H2020-MSCA-RISE PRISAR grant number 644373 and by a grant from MED-EL (Innsbruck, Austria) grant number FK0151/MEDELI001.This project is financially supported by grants from Stichting Het Heinsius-Houbolt Fonds, the Netherlands. Timo Schomann received funding from MED-EL (Innsbruck, Austria). Acknowledgments Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = jul,

day = "1",

doi = "10.1007/s00441-020-03173-1",

language = "English",

volume = "381",

pages = "55--69",

journal = "Cell and Tissue Research",

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T1 - Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury

AU - Schomann, Timo

AU - Iljas, Juvita D.

AU - Que, Ivo

AU - Li, Yuedan

AU - Suidgeest, Ernst

AU - Cruz, Luis J.

AU - Frijns, Johan H.M.

AU - Chan, Alan

AU - Löwik, Clemens M.W.G.

AU - Huisman, Margriet A.

AU - Mezzanotte, Laura

N1 - Funding Information: The authors acknowledge Carola van der Ploeg for technical assistance. We greatly acknowledge Louise van der Weerd (Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands) for support with analysis and interpretation of MRI data. Funding Information: This work was supported by the FP7 European Union Marie Curie IAPP Program, BRAINPATH, under grant number 612360, the project grant H2020-MSCA-RISE PRISAR grant number 644373 and by a grant from MED-EL (Innsbruck, Austria) grant number FK0151/MEDELI001.This project is financially supported by grants from Stichting Het Heinsius-Houbolt Fonds, the Netherlands. Timo Schomann received funding from MED-EL (Innsbruck, Austria). Acknowledgments Publisher Copyright: © 2020, The Author(s).

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Traumatic brain injury (TBI) is a devastating event for which current therapies are limited. Stem cell transplantation may lead to recovery of function via different mechanisms, such as cell replacement through differentiation, stimulation of angiogenesis and support to the microenvironment. Adult hair follicle bulge-derived stem cells (HFBSCs) possess neuronal differentiation capacity, are easy to harvest and are relatively immune-privileged, which makes them potential candidates for autologous stem cell-based therapy. In this study, we apply in vivo multimodal, optical and magnetic resonance imaging techniques to investigate the behavior of mouse HFBSCs in a mouse model of TBI. HFBSCs expressed Luc2 and copGFP and were examined for their differentiation capacity in vitro. Subsequently, transduced HFBSCs, preloaded with ferumoxytol, were transplanted next to the TBI lesion (cortical region) in nude mice, 2 days after injury. Brains were fixed for immunohistochemistry 58 days after transplantation. Luc2- and copGFP-expressing, ferumoxytol-loaded HFBSCs showed adequate neuronal differentiation potential in vitro. Bioluminescence of the lesioned brain revealed survival of HFBSCs and magnetic resonance imaging identified their localization in the area of transplantation. Immunohistochemistry showed that transplanted cells stained for nestin and neurofilament protein (NF-Pan). Cells also expressed laminin and fibronectin but extracellular matrix masses were not detected. After 58 days, ferumoxytol could be detected in HFBSCs in brain tissue sections. These results show that HFBSCs are able to survive after brain transplantation and suggest that cells may undergo differentiation towards a neuronal cell lineage, which supports their potential use for cell-based therapy for TBI.

AB - Traumatic brain injury (TBI) is a devastating event for which current therapies are limited. Stem cell transplantation may lead to recovery of function via different mechanisms, such as cell replacement through differentiation, stimulation of angiogenesis and support to the microenvironment. Adult hair follicle bulge-derived stem cells (HFBSCs) possess neuronal differentiation capacity, are easy to harvest and are relatively immune-privileged, which makes them potential candidates for autologous stem cell-based therapy. In this study, we apply in vivo multimodal, optical and magnetic resonance imaging techniques to investigate the behavior of mouse HFBSCs in a mouse model of TBI. HFBSCs expressed Luc2 and copGFP and were examined for their differentiation capacity in vitro. Subsequently, transduced HFBSCs, preloaded with ferumoxytol, were transplanted next to the TBI lesion (cortical region) in nude mice, 2 days after injury. Brains were fixed for immunohistochemistry 58 days after transplantation. Luc2- and copGFP-expressing, ferumoxytol-loaded HFBSCs showed adequate neuronal differentiation potential in vitro. Bioluminescence of the lesioned brain revealed survival of HFBSCs and magnetic resonance imaging identified their localization in the area of transplantation. Immunohistochemistry showed that transplanted cells stained for nestin and neurofilament protein (NF-Pan). Cells also expressed laminin and fibronectin but extracellular matrix masses were not detected. After 58 days, ferumoxytol could be detected in HFBSCs in brain tissue sections. These results show that HFBSCs are able to survive after brain transplantation and suggest that cells may undergo differentiation towards a neuronal cell lineage, which supports their potential use for cell-based therapy for TBI.

UR - https://www.scopus.com/pages/publications/85079436774

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DO - 10.1007/s00441-020-03173-1

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JO - Cell and Tissue Research

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ER -

Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury

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