A coaxially extruded heterogeneous core–shell fiber with Schwann cells and neural stem cells

Li, Xinda; Zhou, Dezhi; Jin, Zhizhong; Chen, Hongqing; Wang, Xuanzhi; Zhang, Xinzhi; Xu, Tao

doi:10.1093/rb/rbz037

Cited by 14 publications

(25 citation statements)

References 29 publications

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“…NSCs in our bioprinted co-axial AD model constructs presented not only self-renewal characterized by expression of stemness (Nestin, SOX2) markers and significant gene expression (Nestin) but also stem cell differentiation with expression of neuronal (Tubulin) and astrocyte (GFAP, ALDH1L1) markers as well as higher Tubulin and GFAP gene expression compared to 2D and MIX control groups. These results demonstrate that the 3D co-axial microenvironment provided a barrier-free core part for cell self-assembling growth and differentiation, consistent with previous reports [ 34 ]. However, MAP2, another neuronal marker, did not be detected by IF analysis.…”

Section: Discussionsupporting

confidence: 93%

Three-dimensional-engineered bioprinted in vitro human neural stem cell self-assembling culture model constructs of Alzheimer's disease

Zhang

Chen

Long

et al. 2022

Bioactive Materials

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The pathogenic cascade of Alzheimer's disease (AD) characterized by amyloid-β protein accumulation is still poorly understood, partially owing to the limitations of relevant models without in vivo neural tissue microenvironment to recapitulate cell–cell interactions. To better mimic neural tissue microenvironment, three-dimensional (3D) core-shell AD model constructs containing human neural progenitor cells (NSCs) with 2% matrigel as core bioink and 2% alginate as shell bioink have been bioprinted by a co-axial bioprinter, with a suitable shell thickness for nutrient exchange and barrier-free cell interaction cores. These constructs exhibit cell self-clustering and -assembling properties and engineered reproducibility with long-term cell viability and self-renewal, and a higher differentiation level compared to 2D and 3D MIX models. The different effects of 3D bioprinted, 2D, and MIX microenvironments on the growth of NSCs are mainly related to biosynthesis of amino acids and glyoxylate and dicarboxylate metabolism on day 2 and ribosome, biosynthesis of amino acids and proteasome on day 14. Particularly, the model constructs demonstrated Aβ aggregation and higher expression of Aβ and tau isoform genes compared to 2D and MIX controls. AD model constructs will provide a promising strategy to facilitate the development of a 3D in vitro AD model for neurodegeneration research.

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Section: Discussionsupporting

confidence: 93%

Three-dimensional-engineered bioprinted in vitro human neural stem cell self-assembling culture model constructs of Alzheimer's disease

Zhang

Chen

Long

et al. 2022

Bioactive Materials

Self Cite

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“…This observation was further supported by quantifying axon length for PC-12 cells at day 7 ( Figure 5 B), which may be caused by neurotrophic factors being secreted by SCs [ 13 , 14 ]. Indeed, the enhanced differentiation of neural stem cells has been observed in SC-neuron co-cultures [ 52 , 53 ]. Furthermore, the fluorescence intensity of βIII tubulin for PC-12 cells in co-culture was also determined to quantify the protein expression ( Figure 5 C), suggesting that PC-12 cells in co-culture had significantly higher βIII tubulin expression than the control group.…”

Section: Resultsmentioning

confidence: 99%

Promotion of Adrenal Pheochromocytoma (PC-12) Cell Proliferation and Outgrowth Using Schwann Cell-Laden Gelatin Methacrylate Substrate

Huang

Liu

et al. 2022

Gels

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Peripheral nerve injuries cause different degrees of nerve palsy and function loss. Due to the limitations of autografts, nerve tissue engineering (TE) scaffolds incorporated with various neurotrophic factors and cells have been investigated to promote nerve regeneration. However, the molecular mechanism is still poorly understood. In this study, we co-cultured Schwann cells (SCs) and rat adrenal pheochromocytoma (PC-12) cells on 50% degrees of methacryloyl substitution gelatin methacrylate (GelMA) scaffold. The SCs were encapsulated within the GelMA, and PC-12 cells were on the surface. A 5% GelMA was used as the co-culture scaffold since it better supports SCs proliferation, viability, and myelination and promotes higher neurotrophic factors secretion than 10% GelMA. In the co-culture, PC-12 cells demonstrated a higher cell proliferation rate and axonal extension than culturing without SCs, indicating that the secretion of neurotrophic factors from SCs can stimulate PC-12 growth and axonal outgrowth. The mRNA level for neurotrophic factors of SCs in 5% GelMA was further evaluated. We found significant upregulation when compared with a 2D culture, which suggested that this co-culture system could be a potential scaffold to investigate the mechanism of how SCs affect neuronal behaviors.

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“…This hydrogel has several advantages of 1) high affinity for various GFs, 2) sustained release of these GFs in a stable manner, 3) protection of GFs from enzymatic hydrolysis, and 4) avoiding the side effects of high concentrations of GFs at the injection site. It has been widely used as a scaffold material for tissue engineering and cell transplantation ( Li et al, 2019 ; Rastogi and Kandasubramanian, 2019 ; Zhang and Zhao, 2020 ). After SCI, a large amount of divalent calcium ions accumulated in the injured area ( Young et al, 1982 ; Young and Koreh, 1986 ; Singh et al, 2019 ), and provided a natural gelatinizing environment for sodium alginate.…”

Section: Introductionmentioning

confidence: 99%

ALG-bFGF Hydrogel Inhibiting Autophagy Contributes to Protection of Blood–Spinal Cord Barrier Integrity via PI3K/Akt/FOXO1/KLF4 Pathway After SCI

Zhang

Xie

et al. 2022

Front. Pharmacol.

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Promoting blood–spinal cord barrier (BSCB) repair at the early stage plays a crucial role in treatment of spinal cord injury (SCI). Excessive activation of autophagy can prevent recovery of BSCB after SCI. Basic fibroblast growth factor (bFGF) has been shown to promote BSCB repair and locomotor function recovery in SCI. However, the therapeutic effect of bFGF via direct administration on SCI is limited because of its rapid degradation and dilution at injury site. Based on these considerations, controlled release of bFGF in the lesion area is becoming an attractive strategy for SCI repair. At present, we have designed a sustained-release system of bFGF (called ALG-bFGF) using sodium alginate hydrogel, which is able to load large amounts of bFGF and suitable for in situ administration of bFGF in vivo. Here, traumatic SCI mice models and oxygen glucose deprivation (OGD)–stimulated human brain microvascular endothelial cells were performed to explore the effects and the underlying mechanisms of ALG-bFGF in promoting SCI repair. After a single in situ injection of ALG-bFGF hydrogel into the injured spinal cord, sustained release of bFGF from ALG hydrogel distinctly prevented BSCB destruction and improved motor functional recovery in mice after SCI, which showed better therapeutic effect than those in mice treated with bFGF solution or ALG. Evidences have demonstrated that autophagy is involved in maintaining BSCB integrity and functional restoration in animals after SCI. In this study, SCI/OGD exposure–induced significant upregulations of autophagy activation-related proteins (Beclin1, ATG5, LC3II/I) were distinctly decreased by ALG-bFGF hydrogel near the baseline and not less than it both in vivo and in vitro, and this inhibitory effect contributed to prevent BSCB destruction. Finally, PI3K inhibitor LY294002 and KLF4 inhibitor NSC-664704 were applied to further explore the underlying mechanism by which ALG-bFGF attenuated autophagy activation to alleviate BSCB destruction after SCI. The results further indicated that ALG-bFGF hydrogel maintaining BSCB integrity by inhibiting autophagy activation was regulated by PI3K/Akt/FOXO1/KLF4 pathway. In summary, our current study revealed a novel mechanism by which ALG-bFGF hydrogel improves BSCB and motor function recovery after SCI, providing an effective therapeutic strategy for SCI repair.

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A coaxially extruded heterogeneous core–shell fiber with Schwann cells and neural stem cells

Cited by 14 publications

References 29 publications

Three-dimensional-engineered bioprinted in vitro human neural stem cell self-assembling culture model constructs of Alzheimer's disease

Three-dimensional-engineered bioprinted in vitro human neural stem cell self-assembling culture model constructs of Alzheimer's disease

Promotion of Adrenal Pheochromocytoma (PC-12) Cell Proliferation and Outgrowth Using Schwann Cell-Laden Gelatin Methacrylate Substrate

ALG-bFGF Hydrogel Inhibiting Autophagy Contributes to Protection of Blood–Spinal Cord Barrier Integrity via PI3K/Akt/FOXO1/KLF4 Pathway After SCI

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