2018 Fiscal Year Annual Research Report
Inhibiting Scar Development for Promoting Stem Cell Engraftment in Chronic Spinal Cord Injuries.
| Project/Area Number |
16K21360
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
ルノー三原 フランソワ 慶應義塾大学, 医学部(信濃町), 特任講師 (20570427)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Keywords | Spinal cord injury / reactive astrocytes / glial scar / chronic scar / stem cell / STAT3 / RhoA |
|---|
| Outline of Annual Research Achievements |
#1: Effects of molecule X in spinal cord injury. We found that molecule X, regulates the expression of several proteases and induces lesion remodeling, but the survival rate and distribution of transplanted neural stem cells are unchanged, which led us to abandon this research theme.
#2 The characterization of the gene expression profile of lesion scar-forming reactive astrocytes has been reported by another Japanese research group (Hara M. et al., Nature Medicine, 2017 Jul;23(7):818-828) before we could complete our own study.
#3: We found that the transcription factor STAT3 regulates the dynamics of reactive astrocytes in vitro and glial scar formation in vivo. We have shown that regulation of the GTPase RhoA by STAT3 modulates glial scar formation in vivo. This study is published in the Journal of Cell Biology (Renault-Mihara et al., 2017, PMID: 28642362).
#4: Central nervous system healing mechanisms. Two different experimental models were used to characterize novel markers of pathological nerve scars. This marker is not seen in simulated animals. Interestingly, this marker is also expressed in wild-type mice in the chronic phase of spinal cord injury, which may indicate that this marker is useful in the study of the incomplete healing that characterizes neural tissue. By comparing gene expression levels in these different models, we are trying to identify candidate genes responsible for the emergence of this marker. Our hypothesis is that these genes may be associated with incomplete healing in the central nervous system. This study is still in progress.
|
| Remarks |
The research done is somehow different from the proposed project, but has brought significant results in directly related areas (glial scar after spinal cord injury, and markers of chronic scars).
|
Research Products
(3 results)
-
[Journal Article] Selective Ablation of Tumorigenic Cells Following Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation in Spinal Cord Injury.2019
Author(s)
Kojima K, Miyoshi H, Nagoshi N, Kohyama J, Itakura G, Kawabata S, Ozaki M, Iida T, Sugai K, Ito S, Fukuzawa R, Yasutake K, Renault-Mihara F, Shibata S, Matsumoto M, Nakamura M, Okano H
-
Journal Title
Stem Cells Transl Med
Volume: 8
Pages: 260-270
DOI
Peer Reviewed / Int'l Joint Research
-
[Journal Article] CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations.2018
Author(s)
Okuno H, Renault Mihara F, Ohta S, Fukuda K, Kurosawa K, Akamatsu W, Sanosaka T, Kohyama J, Hayashi K, Nakajima K, Takahashi T, Wysocka J, Kosaki K, Okano H.
-
Journal Title
Elife
Volume: 6
Pages: 23-24
DOI
Peer Reviewed / Int'l Joint Research
-
