Colloids as mobile substrates for the implantation and integration of differentiated neurons into the mammalian brain

Dennis Jgamadze, Jamie Bergen, Daniel Stone, Jae-Hyung Jang, David V. Schaffer, Ehud Y. Isacoff, Sophie Pautot

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and there have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is that differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture growth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these problems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even transfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The transplanted cells have a 76% cell survival rate one week post-surgery. At this time, most transplanted neurons have left their beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute uniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the transplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation, calcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host neurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell survival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach, which could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising prospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons.

Original languageEnglish
Article numbere30293
JournalPLoS One
Volume7
Issue number1
DOIs
Publication statusPublished - 2012 Jan 25

Fingerprint

colloids
Colloids
Ion implantation
Neurons
Brain
neurons
brain
Substrates
cells
Transplants
hippocampus
cell viability
Rats
Hippocampus
Cell Survival
Transplantation
Cells
Neural Stem Cells
Photoexcitation
rats

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Jgamadze, Dennis ; Bergen, Jamie ; Stone, Daniel ; Jang, Jae-Hyung ; Schaffer, David V. ; Isacoff, Ehud Y. ; Pautot, Sophie. / Colloids as mobile substrates for the implantation and integration of differentiated neurons into the mammalian brain. In: PLoS One. 2012 ; Vol. 7, No. 1.
@article{e05819ee92334131a71af668687c58e5,
title = "Colloids as mobile substrates for the implantation and integration of differentiated neurons into the mammalian brain",
abstract = "Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and there have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is that differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture growth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these problems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even transfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The transplanted cells have a 76{\%} cell survival rate one week post-surgery. At this time, most transplanted neurons have left their beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute uniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the transplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation, calcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host neurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell survival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach, which could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising prospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons.",
author = "Dennis Jgamadze and Jamie Bergen and Daniel Stone and Jae-Hyung Jang and Schaffer, {David V.} and Isacoff, {Ehud Y.} and Sophie Pautot",
year = "2012",
month = "1",
day = "25",
doi = "10.1371/journal.pone.0030293",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

Colloids as mobile substrates for the implantation and integration of differentiated neurons into the mammalian brain. / Jgamadze, Dennis; Bergen, Jamie; Stone, Daniel; Jang, Jae-Hyung; Schaffer, David V.; Isacoff, Ehud Y.; Pautot, Sophie.

In: PLoS One, Vol. 7, No. 1, e30293, 25.01.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Colloids as mobile substrates for the implantation and integration of differentiated neurons into the mammalian brain

AU - Jgamadze, Dennis

AU - Bergen, Jamie

AU - Stone, Daniel

AU - Jang, Jae-Hyung

AU - Schaffer, David V.

AU - Isacoff, Ehud Y.

AU - Pautot, Sophie

PY - 2012/1/25

Y1 - 2012/1/25

N2 - Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and there have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is that differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture growth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these problems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even transfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The transplanted cells have a 76% cell survival rate one week post-surgery. At this time, most transplanted neurons have left their beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute uniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the transplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation, calcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host neurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell survival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach, which could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising prospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons.

AB - Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and there have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is that differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture growth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these problems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even transfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The transplanted cells have a 76% cell survival rate one week post-surgery. At this time, most transplanted neurons have left their beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute uniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the transplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation, calcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host neurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell survival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach, which could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising prospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons.

UR - http://www.scopus.com/inward/record.url?scp=84856245760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856245760&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0030293

DO - 10.1371/journal.pone.0030293

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e30293

ER -