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Research
Ruxiang Xu
Sichuan Academy of Medical Sciences and Sichuan People's Hospital
Corresponding Author
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Background
Recently, growing evidence has indicated an important role of the complement system, a crucial component of immunity, in mediating neuroinflammation and promoting neuronal apoptosis following closed head injury (CHI). We previously reported that transplanted induced neural stem cells (iNSCs) pre-treated with CHI mouse serum could enhance complement receptor type 1-related protein y (Crry) expression and ameliorate complement-mediated damage in mouse CHI models. However, the mechanism underlying the elevated levels of Crry expression remains elusive.
Methods
CHI models were established using a standardized weight-drop device and CHI mouse serum was collected at 12 h post-trauma. Complement deposition assay, Akt inhibition assay, cell viability assay, functional assay, cell transplantation, morphological and molecular biological analyses were performed.
Results
In the present study, we observed dramatic increases in the levels of Crry expression and Akt activation in iNSCs receiving CHI mouse serum treatment. Remarkably, Akt inhibition led to the reduction of Crry expression in iNSCs. Intriguingly, the treatment of iNSC-derived neurons with recombinant complement receptor 2-conjugated Crry (CR2-Crry), which inhibits all complement pathways, substantially enhanced Crry expression and Akt activation in neurons after CHI mouse serum treatment. In subsequent in vitro experiments of pre-treatment of iNSCs with CR2-Crry, we observed significant increases in the levels of Crry expression and Akt activation in iNSCs, iNSC-derived astrocytes and neurons post-treatment with CHI mouse serum. Additionally, an in vivo study showed that intracerebral-transplanted iNSCs pre-treated with CR2-Crry markedly enhanced Crry expression in neurons and protected neurons from complement-dependent damage in the brains of CHI mice.
Conclusions
In summary, iNSCs receiving CR2-Crry pre-treatment increased the levels of Crry expression in iNSCs, iNSC-derived astrocytes and neurons and attenuated complement-mediated injury following CHI.
Keywords
induced neural stem cell, Crry, closed head injury, transplantation, complement
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CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
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Editor assigned
On 19 Jan, 2021
Editorial decision: Accept
On 19 Jan, 2021
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On 19 Jan, 2021
Editor invited
On 19 Jan, 2021
No comments provided
Reviewer #2 agreed
On 14 Jan, 2021
Review #1 received
Received 12 Jan, 2021
Reviewer #1 agreed
On 10 Jan, 2021
Editor assigned
On 05 Jan, 2021
Reviewers invited
Invitations sent on 05 Jan, 2021
Submission checks complete
On 05 Jan, 2021
Editor invited
On 05 Jan, 2021
Version 1
Posted 21 May, 2020
No comments provided
Editorial decision: Major Revision
On 10 Dec, 2020
Review #3 received
Received 09 Dec, 2020
Review #2 received
Received 04 Dec, 2020
Reviewer #3 agreed
On 03 Dec, 2020
Reviewer #2 agreed
On 02 Dec, 2020
Review #1 received
Received 19 Oct, 2020
Reviewer #1 agreed
On 11 Oct, 2020
Reviewers invited
Invitations sent on 04 Jun, 2020
Editor assigned
On 25 May, 2020
Editor invited
On 24 May, 2020
Submission checks complete
On 18 May, 2020
First submitted
On 14 May, 2020
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Subject Areas
Stem Cell & Developmental Cell Biology
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A new preprint design is coming!
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See the published version of this preprint at Stem Cell Research & Therapy.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Ruxiang Xu
Sichuan Academy of Medical Sciences and Sichuan People's Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
No community comments so far
Editor assigned
On 19 Jan, 2021
Editorial decision: Accept
On 19 Jan, 2021
Submission checks complete
On 19 Jan, 2021
Editor invited
On 19 Jan, 2021
No comments provided
Reviewer #2 agreed
On 14 Jan, 2021
Review #1 received
Received 12 Jan, 2021
Reviewer #1 agreed
On 10 Jan, 2021
Editor assigned
On 05 Jan, 2021
Reviewers invited
Invitations sent on 05 Jan, 2021
Submission checks complete
On 05 Jan, 2021
Editor invited
On 05 Jan, 2021
Version 1
Posted 21 May, 2020
No comments provided
Editorial decision: Major Revision
On 10 Dec, 2020
Review #3 received
Received 09 Dec, 2020
Review #2 received
Received 04 Dec, 2020
Reviewer #3 agreed
On 03 Dec, 2020
Reviewer #2 agreed
On 02 Dec, 2020
Review #1 received
Received 19 Oct, 2020
Reviewer #1 agreed
On 11 Oct, 2020
Reviewers invited
Invitations sent on 04 Jun, 2020
Editor assigned
On 25 May, 2020
Editor invited
On 24 May, 2020
Submission checks complete
On 18 May, 2020
First submitted
On 14 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Stem Cell Research & Therapy.
Background
Recently, growing evidence has indicated an important role of the complement system, a crucial component of immunity, in mediating neuroinflammation and promoting neuronal apoptosis following closed head injury (CHI). We previously reported that transplanted induced neural stem cells (iNSCs) pre-treated with CHI mouse serum could enhance complement receptor type 1-related protein y (Crry) expression and ameliorate complement-mediated damage in mouse CHI models. However, the mechanism underlying the elevated levels of Crry expression remains elusive.
Methods
CHI models were established using a standardized weight-drop device and CHI mouse serum was collected at 12 h post-trauma. Complement deposition assay, Akt inhibition assay, cell viability assay, functional assay, cell transplantation, morphological and molecular biological analyses were performed.
Results
In the present study, we observed dramatic increases in the levels of Crry expression and Akt activation in iNSCs receiving CHI mouse serum treatment. Remarkably, Akt inhibition led to the reduction of Crry expression in iNSCs. Intriguingly, the treatment of iNSC-derived neurons with recombinant complement receptor 2-conjugated Crry (CR2-Crry), which inhibits all complement pathways, substantially enhanced Crry expression and Akt activation in neurons after CHI mouse serum treatment. In subsequent in vitro experiments of pre-treatment of iNSCs with CR2-Crry, we observed significant increases in the levels of Crry expression and Akt activation in iNSCs, iNSC-derived astrocytes and neurons post-treatment with CHI mouse serum. Additionally, an in vivo study showed that intracerebral-transplanted iNSCs pre-treated with CR2-Crry markedly enhanced Crry expression in neurons and protected neurons from complement-dependent damage in the brains of CHI mice.
Conclusions
In summary, iNSCs receiving CR2-Crry pre-treatment increased the levels of Crry expression in iNSCs, iNSC-derived astrocytes and neurons and attenuated complement-mediated injury following CHI.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
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