NDLI: Transplanted deep-layer cortical neuroblasts integrate into host neural circuits and alleviate motor defects in hypoxic-ischemic encephalopathy injured mice

Content Provider	Springer Nature : BioMed Central
Author	Wu, Mengnan Xu, Yuan Ji, Xiaoli Zhou, Yingying Li, Yuan Feng, Ban Cheng, Qian He, Hui Peng, Xingsheng Zhou, Wenhao Chen, Yuejun Xiong, Man
Abstract	Background Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although intensive studies and therapeutic approaches, there are limited restorative treatments till now. Human embryonic stem cell (hESCs)-derived cortical neural progenitors have shown great potentials in ischemic stroke in adult brain. However, it is unclear whether they are feasible for cortical reconstruction in immature brain with hypoxic-ischemic encephalopathy. Methods By using embryonic body (EB) neural differentiation method combined with DAPT pre-treatment and quantitative cell transplantation, human cortical neuroblasts were obtained and transplanted into the cortex of hypoxic-ischemic injured brain with different dosages 2 weeks after surgery. Then, immunostaining, whole-cell patch clamp recordings and behavioral testing were applied to explore the graft survival and proliferation, fate commitment of cortical neuroblasts in vitro, neural circuit reconstruction and the therapeutic effects of cortical neuroblasts in HIE brain. Results Transplantation of human cortical neural progenitor cells (hCNPs) in HIE-injured cortex exhibited long-term graft overgrowth. DAPT pre-treatment successfully synchronized hCNPs from different developmental stages (day 17, day 21, day 28) to deep layer cortical neuroblasts which survived well in HIE injured brain and greatly prevented graft overgrowth after transplantation. Importantly, the cortical neuroblasts primarily differentiated into deep-layer cortical neurons and extended long axons to their projection targets, such as the cortex, striatum, thalamus, and internal capsule in both ipsilateral and contralateral HIE-injured brain. The transplanted cortical neurons established synapses with host cortical neurons and exhibited spontaneous excitatory or inhibitory post-synaptic currents (sEPSCs or sIPSCs) five months post-transplantation. Rotarod and open field tests showed greatly improved animal behavior by intra-cortex transplantation of deep layer cortical neuroblasts in HIE injured brain. Conclusions Transplanted hESCs derived cortical neuroblasts survive, project to endogenous targets, and integrate into host cortical neural circuits to rescue animal behavior in the HIE-injured brain without graft overgrowth, providing a novel and safe cell replacement strategy for the future treatment of HIE.
Related Links	https://stemcellres.biomedcentral.com/counter/pdf/10.1186/s13287-024-04049-9.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
ISSN	17576512
DOI	10.1186/s13287-024-04049-9
Journal	Stem Cell Research & Therapy
Issue Number	1
Volume Number	15
Language	English
Publisher	BioMed Central
Publisher Date	2024-11-13
Access Restriction	Open
Subject Keyword	Stem Cells Cell Biology Regenerative Medicine Tissue Engineering Biomedical Engineering and Bioengineering Hypoxic-ischemic encephalopathy Human embryonic stem cells Cortical neuroblasts Cell transplantation Graft overgrowth Neural circuit repair Regenerative Medicine/Tissue Engineering
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Biochemistry, Genetics and Molecular Biology Molecular Medicine
Journal Impact Factor	7.1/2023
5-Year Journal Impact Factor	7.9/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

CCL11 promotes migration and proliferation of mouse neural progenitor cells

CXCL10 is a crucial chemoattractant for efficient intranasal delivery of mesenchymal stem cells to the neonatal hypoxic-ischemic brain

Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts

Correction to: Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts

Highly efficient differentiation of neural precursors from human embryonic stem cells and benefits of transplantation after ischemic stroke in mice

Cell-based treatment for perinatal hypoxic-ischemic encephalopathy

Embryonic stem cell-derived mesenchymal stem cells alleviate skeletal muscle injury induced by acute compartment syndrome

A chitosan/acellular matrix-based neural graft carrying mesenchymal stem cells to promote peripheral nerve repair

Neural tissue engineering using embryonic and induced pluripotent stem cells

Transplanted deep-layer cortical neuroblasts integrate into host neural circuits and alleviate motor defects in hypoxic-ischemic encephalopathy injured mice

Similar Documents

CCL11 promotes migration and proliferation of mouse neural progenitor cells

CXCL10 is a crucial chemoattractant for efficient intranasal delivery of mesenchymal stem cells to the neonatal hypoxic-ischemic brain

Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts

Correction to: Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts

Highly efficient differentiation of neural precursors from human embryonic stem cells and benefits of transplantation after ischemic stroke in mice

Cell-based treatment for perinatal hypoxic-ischemic encephalopathy

Embryonic stem cell-derived mesenchymal stem cells alleviate skeletal muscle injury induced by acute compartment syndrome

A chitosan/acellular matrix-based neural graft carrying mesenchymal stem cells to promote peripheral nerve repair

Neural tissue engineering using embryonic and induced pluripotent stem cells

Transplanted deep-layer cortical neuroblasts integrate into host neural circuits and alleviate motor defects in hypoxic-ischemic encephalopathy injured mice