Caspase-mediated cell death predominates following engraftment of neural progenitor cells into traumatically injured rat brain

Bakshi, Asha; Keck, Carrie A.; Koshkin, Vadim S.; LeBold, David G.; Siman, Robert; Snyder, Evan Y.; McIntosh, Tracy K.

doi:10.1016/j.brainres.2005.09.059

Cited by 77 publications

(70 citation statements)

References 86 publications

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“…33 However, the majority of grafted precursors are subjected to death during the first hours following their transplantation. 16 The death pathways activated upon allografting have not yet been completely understood. Proinflammatory cytokines, 34 necrosis, 35 and caspase-mediated apoptosis 16,36,37 have been mentioned by different authors as a main reason of transplanted precursor cell death.…”

Section: Discussionmentioning

confidence: 99%

“…15 However, a substantial loss of grafted cells usually occurs within the first hours following the transplantation. 16 Because of this, these newly introduced neurons have very low potential to integrate into the neurite network of the recipient. There are some literature data which suggest that the caspase-dependent apoptosis is a predominant reason of neural graft death.…”

mentioning

confidence: 99%

“…There are some literature data which suggest that the caspase-dependent apoptosis is a predominant reason of neural graft death. 16,17 At the same time, it has not yet been tested whether or not such apoptosis occurs by the mitochondrial-dependent pathway. Based on our previous results, we have hypothesized that Bax-induced activation of the mitochondrial apoptotic pathway is a major event, which leads to death of granule cell precursors after their transplantation.…”

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confidence: 99%

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Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

et al. 2008

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Transplantation of neuronal precursor cells (NPCs) into the central nervous system could represent a powerful therapeutical tool against neurodegenerative diseases. Unfortunately, numerous NPCs die shortly after transplantation, predominantly due to caspase-dependent apoptosis. Using a culture of cerebellar neuronal precursors, we have previously demonstrated protective effect of the neuropeptide PACAP, which suppresses ceramide-induced apoptosis by blockade of the mitochondrial apoptotic pathway. The main objective of this study was to determine whether Bax repression can promote survival of NPCs allotransplanted into a host animal. In vivo and ex vivo experiments revealed that C2-ceramide increases Bax expression, while PACAP reverses this effect. In vitro tests using cerebellar NPCs demonstrated that the Bax-specific small interfering RNA (siRNA) could reduce their death and caspase-3 cleavage within the first 24 h. BrdU-labelled NPCs were subjected to transfection procedure with or without siRNA introduction before using for in vivo transplantation. Twenty-four hours after, the allografted NPCs containing siRNA showed significantly reduced level of caspase-3 cleavage, and the volume of their implants was almost twofold higher than in the case of empty-transfected precursors. These data evidence an important role of Bax in life/death decision of grafted NPCs and suggest that RNA interference strategy may be applicable for maintaining NPCs survival within the critical first hours after their transplantation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

et al. 2008

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“…However, most of the NCs transplanted to the injury environment do not survive and cells that do survive do not display integrative behavior. Only 2-4.5% of mouse NPCs transplanted into rats after traumatic brain injury survived 24 h after the transplant (Bakshi et al, 2005). In addition, the caspase activity of transplanted NPCs that survived was higher in injured rats than sham surgery controls, indicating that the population of cells that survived was apoptotic in the CNS injury environment (Bakshi et al, 2005).…”

Section: Reparative Effects Of Endogenous Ncsmentioning

confidence: 99%

“…Only 2-4.5% of mouse NPCs transplanted into rats after traumatic brain injury survived 24 h after the transplant (Bakshi et al, 2005). In addition, the caspase activity of transplanted NPCs that survived was higher in injured rats than sham surgery controls, indicating that the population of cells that survived was apoptotic in the CNS injury environment (Bakshi et al, 2005). While transplanted cell viability is higher if the transplant is performed 1 week postinjury (Hill et al, 2006;Walker et al, 2015), NCs alone do not restore functionality to preinjury baselines.…”

Section: Reparative Effects Of Endogenous Ncsmentioning

confidence: 99%

Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

Meco

Lampe

2018

Front. Mater.

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Biomaterial scaffolds mimic aspects of the native central nervous system (CNS) extracellular matrix (ECM) and have been extensively utilized to influence neural cell (NC) behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and three-dimensional (3D) bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues.

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When Bio Meets Technology: Biohybrid Neural Interfaces

et al. 2019

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The development of electronics capable of interfacing with the nervous system is a rapidly advancing field with applications in basic science and clinical translation. Devices containing arrays of electrodes can be used in the study of cells grown in culture or can be implanted into damaged or dysfunctional tissue to restore normal function. While devices are typically designed and used exclusively for one of these two purposes, there have been increasing efforts in developing implantable electrode arrays capable of housing cultured cells, referred to as biohybrid implants. Once implanted, the cells within these implants integrate into the tissue, serving as a mediator of the electrode–tissue interface. This biological component offers unique advantages to these implant designs, providing better tissue integration and potentially long‐term stability. Herein, an overview of current research into biohybrid devices, as well as the historical background that led to their development are provided, based on the host anatomical location for which they are designed (CNS, PNS, or special senses). Finally, a summary of the key challenges of this technology and potential future research directions are presented.

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Caspase-mediated cell death predominates following engraftment of neural progenitor cells into traumatically injured rat brain

Cited by 77 publications

References 86 publications

Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

When Bio Meets Technology: Biohybrid Neural Interfaces

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