Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model

Cell transplantation therapy is a promising strategy for spinal cord injury (SCI) repair. Despite advancements in the development of therapeutic strategies in acute and subacute SCI, much less is known about effective strategies for chronic SCI. In previous studies we demonstrated that transplants o...

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Main Authors: Kazuo Hayakawa, Ying Jin, Julien Bouyer, Theresa M. Connors, Takanobu Otsuka, Itzhak Fischer
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/2/350
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author Kazuo Hayakawa
Ying Jin
Julien Bouyer
Theresa M. Connors
Takanobu Otsuka
Itzhak Fischer
author_facet Kazuo Hayakawa
Ying Jin
Julien Bouyer
Theresa M. Connors
Takanobu Otsuka
Itzhak Fischer
author_sort Kazuo Hayakawa
collection DOAJ
description Cell transplantation therapy is a promising strategy for spinal cord injury (SCI) repair. Despite advancements in the development of therapeutic strategies in acute and subacute SCI, much less is known about effective strategies for chronic SCI. In previous studies we demonstrated that transplants of neural progenitor cells (NPC) created a permissive environment for axon regeneration and formed a neuronal relay across the injury following an acute dorsal column injury. Here we explored the efficacy of such a strategy in a chronic injury. We tested two preparations of NPCs derived from rat spinal cord at embryonic day 13.5: one prepared using stocks of cultured cells and the other of dissociated cells transplanted without culturing. Transplantation was delayed for 4-, 6- and 12-weeks post injury for a chronic injury model. We found that the dissociated NPC transplants survived and proliferated for at least 5 weeks post transplantation, in contrast to the poor survival of transplants prepared from cultured NPC stocks. The dissociated NPC transplants differentiated into neurons expressing excitatory markers, promoted axon regeneration into the injury/transplant site and extended axons from graft-derived neurons into the host. These results support the potential of NPC transplants to form neuronal relays across a chronic SCI, but they also underscore the challenges of achieving efficient cell survival in the environment of a chronic injury.
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spelling doaj.art-ba573196c9eb4ba091554eb3ad45b7b62023-11-23T18:54:14ZengMDPI AGBiomedicines2227-90592022-02-0110235010.3390/biomedicines10020350Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion ModelKazuo Hayakawa0Ying Jin1Julien Bouyer2Theresa M. Connors3Takanobu Otsuka4Itzhak Fischer5Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USADepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USADepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USADepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USADepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, JapanDepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USACell transplantation therapy is a promising strategy for spinal cord injury (SCI) repair. Despite advancements in the development of therapeutic strategies in acute and subacute SCI, much less is known about effective strategies for chronic SCI. In previous studies we demonstrated that transplants of neural progenitor cells (NPC) created a permissive environment for axon regeneration and formed a neuronal relay across the injury following an acute dorsal column injury. Here we explored the efficacy of such a strategy in a chronic injury. We tested two preparations of NPCs derived from rat spinal cord at embryonic day 13.5: one prepared using stocks of cultured cells and the other of dissociated cells transplanted without culturing. Transplantation was delayed for 4-, 6- and 12-weeks post injury for a chronic injury model. We found that the dissociated NPC transplants survived and proliferated for at least 5 weeks post transplantation, in contrast to the poor survival of transplants prepared from cultured NPC stocks. The dissociated NPC transplants differentiated into neurons expressing excitatory markers, promoted axon regeneration into the injury/transplant site and extended axons from graft-derived neurons into the host. These results support the potential of NPC transplants to form neuronal relays across a chronic SCI, but they also underscore the challenges of achieving efficient cell survival in the environment of a chronic injury.https://www.mdpi.com/2227-9059/10/2/350neuronal progenitor cellschronic spinal cord injurycell transplantationsensory systemaxon regeneration
spellingShingle Kazuo Hayakawa
Ying Jin
Julien Bouyer
Theresa M. Connors
Takanobu Otsuka
Itzhak Fischer
Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model
Biomedicines
neuronal progenitor cells
chronic spinal cord injury
cell transplantation
sensory system
axon regeneration
title Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model
title_full Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model
title_fullStr Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model
title_full_unstemmed Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model
title_short Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model
title_sort transplanting neural progenitor cells into a chronic dorsal column lesion model
topic neuronal progenitor cells
chronic spinal cord injury
cell transplantation
sensory system
axon regeneration
url https://www.mdpi.com/2227-9059/10/2/350
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