scholarly journals Transplantation of neural stem cells encapsulated in hydrogels improve functional recovery in a cauda equina lesion model

2020 ◽  
Author(s):  
Zhiyi Fu ◽  
Huidong Wang ◽  
Yujie Wu ◽  
Tong Zhu
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Functional Recovery ◽  
Cauda Equina ◽  
Three Dimensional ◽  
Stem Cell Differentiation ◽  
Blue Staining ◽  
Tail Flick ◽  
Pathological Changes ◽  
Cauda Equina Lesion

Abstract Background This study explored the therapeutic effects of transplantation of neural stem cells (NSCs) encapsulated in hydrogels in a cauda equina lesion model.Methods NSCs were isolated from neonatal dorsal root ganglion (DRG) and cultured in three-dimensional porous hydrogel scaffolds. Immunohistochemistry, transmission electron microscopy, Luxol fast blue staining, TUNEL assay were performed to detect the differentiation capability, ultrastructural and pathological changes, and apoptosis of NSCs. Furthermore, the functional recovery of sensorimotor reflexes was determined using the tail-flick test.Results NSCs derived from DRG were able to proliferate to form neurospheres and mainly differentiate into oligodendrocytes in the three-dimensional hydrogel culture system. After transplantation of NSCs encapsulated in hydrogels, NSCs differentiated into oligodendrocytes, neurons or astrocytes in vivo . Moreover, NSCs engrafted on the hydrogels decreased apoptosis and alleviated the ultrastructural and pathological changes of injured cauda equina. Behavioral analysis showed that transplanted hydrogel-encapsulated NSCs decreased the tail-flick latency and showed a neuroprotective role on injured cauda equina.Conclusions Our results indicate transplantation of hydrogel-encapsulated NSCs promotes stem cell differentiation into oligodendrocytes, neurons or astrocytes and contributes to the functional recovery of injured cauda equina, suggesting that NSCs encapsulated in hydrogels may be applied for the treatment of cauda equina injury.

scholarly journals Transplantation of neural stem cells encapsulated in hydrogels improve functional recovery in a cauda equina lesion model

2020 ◽  
Author(s):  
Zhiyi Fu ◽  
Huidong Wang ◽  
Yujie Wu ◽  
Tong Zhu
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Functional Recovery ◽  
Cauda Equina ◽  
Three Dimensional ◽  
Stem Cell Differentiation ◽  
Blue Staining ◽  
Tail Flick ◽  
Pathological Changes ◽  
Cauda Equina Lesion

Abstract Background This study explored the therapeutic effects of transplantation of neural stem cells (NSCs) encapsulated in hydrogels in a cauda equina lesion model. Methods NSCs were isolated from neonatal dorsal root ganglion (DRG) and cultured in three-dimensional porous hydrogel scaffolds. Immunohistochemistry, transmission electron microscopy, Luxol fast blue staining, TUNEL assay were performed to detect the differentiation capability, ultrastructural and pathological changes, and apoptosis of NSCs. Furthermore, the functional recovery of sensorimotor reflexes was determined using the tail-flick test. Results NSCs derived from DRG were able to proliferate to form neurospheres and mainly differentiate into oligodendrocytes in the three-dimensional hydrogel culture system. After transplantation of NSCs encapsulated in hydrogels, NSCs differentiated into oligodendrocytes, neurons or astrocytes in vivo . Moreover, NSCs engrafted on the hydrogels decreased apoptosis and alleviated the ultrastructural and pathological changes of injured cauda equina. Behavioral analysis showed that transplanted hydrogel-encapsulated NSCs decreased the tail-flick latency and showed a neuroprotective role on injured cauda equina. Conclusions Our results indicate transplantation of hydrogel-encapsulated NSCs promotes stem cell differentiation into oligodendrocytes, neurons or astrocytes and contributes to the functional recovery of injured cauda equina, suggesting that NSCs encapsulated in hydrogels may be applied for the treatment of cauda equina injury.

scholarly journals Improved biocompatibility and efficient labeling of neural stem cells with poly(L-lysine)-coated maghemite nanoparticles

2016 ◽  
Vol 7 ◽  
pp. 926-936 ◽  
Author(s):  
Igor M Pongrac ◽  
Marina Dobrivojević ◽  
Lada Brkić Ahmed ◽  
Michal Babič ◽  
Miroslav Šlouf ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cellular Uptake ◽  
Cell Tracking ◽  
Cellular Migration ◽  
Cell Labeling ◽  
Blue Staining ◽  
Maghemite Nanoparticles ◽  
Acetoxymethyl Ester

Background: Cell tracking is a powerful tool to understand cellular migration, dynamics, homing and function of stem cell transplants. Nanoparticles represent possible stem cell tracers, but they differ in cellular uptake and side effects. Their properties can be modified by coating with different biocompatible polymers. To test if a coating polymer, poly(L-lysine), can improve the biocompatibility of nanoparticles applied to neural stem cells, poly(L-lysine)-coated maghemite nanoparticles were prepared and characterized. We evaluated their cellular uptake, the mechanism of internalization, cytotoxicity, viability and proliferation of neural stem cells, and compared them to the commercially available dextran-coated nanomag®-D-spio nanoparticles. Results: Light microscopy of Prussian blue staining revealed a concentration-dependent intracellular uptake of iron oxide in neural stem cells. The methyl thiazolyl tetrazolium assay and the calcein acetoxymethyl ester/propidium iodide assay demonstrated that poly(L-lysine)-coated maghemite nanoparticles scored better than nanomag®-D-spio in cell labeling efficiency, viability and proliferation of neural stem cells. Cytochalasine D blocked the cellular uptake of nanoparticles indicating an actin-dependent process, such as macropinocytosis, to be the internalization mechanism for both nanoparticle types. Finally, immunocytochemistry analysis of neural stem cells after treatment with poly(L-lysine)-coated maghemite and nanomag®-D-spio nanoparticles showed that they preserve their identity as neural stem cells and their potential to differentiate into all three major neural cell types (neurons, astrocytes and oligodendrocytes). Conclusion: Improved biocompatibility and efficient cell labeling makes poly(L-lysine)-coated maghemite nanoparticles appropriate candidates for future neural stem cell in vivo tracking studies.

Transplantation of collagen sponge-based three-dimensional neural stem cells cultured in the RCCS system facilitate locomotor functional recovery in spinal cord injury animals

2022 ◽  
Author(s):  
Jianwu Dai ◽  
Yunlong Zou ◽  
Yanyun Yin ◽  
Zhifeng Xiao ◽  
Yannan Zhao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
Three Dimensional ◽  
Collagen Sponge ◽  
Cellular Functions ◽  
Cord Injury ◽  
Cells Cultured

Numerous studies have indicated that microgravity induces various changes in the cellular functions of neural stem cells (NSCs), and the use of microgravity to culture tissue engineering seed cells for...

CBIO-05. SOX2 CHROMATIN ARCHITECTURE AND ENHANCER ACTIVITY IN THE MAINTENANCE AND DEVELOPMENT OF NEURAL STEM CELLS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi28-vi28
Author(s):  
Devin Bready ◽  
Aram Modrek ◽  
Joshua Frenster ◽  
Jane Skok ◽  
Dimitris Placantonakis
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Developmental Process ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Ctcf Binding ◽  
Low Grade ◽  
Lower Grade ◽  
Cell Of Origin ◽  
Putative Enhancer

Abstract Gain of function mutations in isocitrate dehydrogenase I (IDH1) result in the formation of the oncometabolite 2-hydroxyglutarate (2HG) in adult lower grade gliomas. To gain insight into mechanisms of gliomagenesis, our lab previously created a tractable human cellular model of low grade astrocytoma (LGA) using the putative cell-of-origin, human neural stem cells (NSCs), engineered to express mutant IDH1 and knockdown constructs against TP53 and ATRX, the two other genetic changes that accompany the IDH mutation in these tumors. We found that transcription factor (sex determining region Y)-box 2 SOX2, which is essential to NSC multipotency, the ability to differentiate to neuroglial lineages, behaves as a tumor suppressor during glioma initiation. In this context, we showed SOX2 is transcriptionally downregulated to impair NSC multipotency, thus locking NSCs in an undifferentiated state to initiate gliomagenesis. This downregulation occurs secondary to dynamic reorganization of the topologically associating domain (TAD) of SOX2 and the loss of contact with several genomic loci with histone modifications and chromatin accessibility suggestive of being enhancers. Here we show that those putative enhancers acquire enhancer-like features simultaneous to tje TAD organizing in a way that facilitates interaction with the SOX2 promoter during the process of pluripotent stem cell differentiation into neuroectodermal lineages, suggesting a developmental role. Preliminary data suggests that disruption of the SOX2 TAD by preventing binding of the genome organizer CTCF downregulates SOX2 expression in NSCs. Targeted silencing of several regions of a putative enhancer with CRISPRi also downregulates SOX2. In human embryonic stem cells (hESCs), interfering with these CTCF binding sites biases their differentiation away from the neuroectoderm. We are currently performing CRISPRi screen against all putative enhancer loci, teratoma formation assays on hESCs lacking relevant CTCF binding, and CRISPR mediated deletion of putative enhancers. Understanding this developmental process may reveal underlying vulnerabilities in LGA.

A Novel Three-Dimensional Culture System for Isolation and Clonal Propagation of Neural Stem Cells Using a Thermo-Reversible Gelation Polymer

2009 ◽  
Vol 15 (4) ◽  
pp. 615-623 ◽  
Author(s):  
Xin-Zhi Yang ◽  
Ken Kataoka ◽  
Reinhold Medina ◽  
Ken-Ichi Yamamoto ◽  
Swe Swe Than ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Culture System ◽  
Clonal Propagation ◽  
Three Dimensional ◽  
Three Dimensional Culture
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