Dataset Information

Therapeutic Effect of Biomimetic Scaffold Loaded with Human Amniotic Epithelial Cell-Derived Neural-like Cells for Spinal Cord Injury.

ABSTRACT: Spinal cord injury (SCI) results in devastating consequences for the motor and sensory function of patients due to neuronal loss and disrupted neural circuits, confronting poor prognosis and lack of effective therapies. A new therapeutic strategy is urgently required. Here, human amniotic epithelial cells (hAEC), featured with immunocompatibility, non-tumorgenicity and no ethical issues, were induced into neural-like cells by a compound cocktail, as evidenced with morphological change and the expression of neural cell markers. Interestingly, the hAEC-neural-like cells maintain the characteristic of low immunogenicity as hAEC. Aiming at SCI treatment in vivo, we constructed a 3D-printed GelMA hydrogel biomimetic spinal cord scaffold with micro-channels, in which hAEC-neural-like cells were well-induced and grown. In a rat full transection SCI model, hAEC-neural-like cell scaffolds that were implanted in the lesion demonstrated significant therapeutic effects; the neural circuit and hindlimb locomotion were partly recovered compared to little affection in the SCI rats receiving an empty scaffold or a sham implantation operation. Thus, the establishment of hAEC-neural-like cell biomimetic scaffolds may provide a safe and effective treatment strategy for SCI.

SUBMITTER: Qiu C

PROVIDER: S-EPMC9598945 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Therapeutic Effect of Biomimetic Scaffold Loaded with Human Amniotic Epithelial Cell-Derived Neural-like Cells for Spinal Cord Injury.

Qiu Chen C Sun Yuan Y Li Jinying J Xu Yuchen Y Zhou Jiayi J Qiu Cong C Zhang Shaomin S He Yong Y Yu Luyang L

Bioengineering (Basel, Switzerland) 20221009 10

Spinal cord injury (SCI) results in devastating consequences for the motor and sensory function of patients due to neuronal loss and disrupted neural circuits, confronting poor prognosis and lack of effective therapies. A new therapeutic strategy is urgently required. Here, human amniotic epithelial cells (hAEC), featured with immunocompatibility, non-tumorgenicity and no ethical issues, were induced into neural-like cells by a compound cocktail, as evidenced with morphological change and the ex ...[more]

PMID: 36290504

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Project description:ObjectiveSpinal cord injury (SCI) is a severe and permanent nerve damage condition that poses significant burdens on individuals and society. Various therapeutic approaches have been explored to mitigate the consequences of SCI. Tissue engineering and regenerative medicine have emerged as a promising avenue for addressing this issue. This study aims to investigate the potential of a nanochitosan/polypyrrole-alginate conductive scaffold, loaded with the Noggin growth factor, an inhibitor of BMP-4 signaling, and human amniotic epithelial cells (hAECs), in promoting the regeneration of SCI in animal models.MethodsThe attachment and distribution of isolated hAECs on a fabricated nanochitosan/polypyrrole-alginate conductive scaffold were assessed using SEM. Additionally, the neural differentiation of hAECs on the scaffold was investigated by analyzing the expression of specific neuronal (Calca, Fox3), oligodendrocyte (MBP), and astrocyte (GFAP) genes in vitro. To evaluate the combined effect of the scaffold and Noggin growth factor in animal models, a Noggin-loaded scaffold was designed using bioinformatics, and the loading and release capacity of Noggin were measured. For in vivo studies, rats underwent laminectomy and were transplanted with the scaffold, either alone or with Noggin and DII labeled- hAECs, at the T10-T11 level. Motor functions of the animal were evaluated using BBB scoring weekly in an open field for four weeks. Furthermore, the expression of neural genes and immunohistochemical tests were evaluated after four weeks.ResultshAECs exhibited uniform distribution and attachment to the scaffold. In vitro differentiation analyses showed increased expression of Calca, Fox3, MBP, and GFAP genes. Docking results indicated that Noggin could interact with chitosan nanoparticles through hydrogen bonds. The chitosan nanoparticles effectively loaded 22.6% of exposed Noggin, and the scaffold released 28.5% of the total incorporated Noggin. In vivo studies demonstrated that transplanting nanochitosan/polypyrrole-alginate conductive scaffolds with DII labeled-hAECs, with or without Noggin, improved motor functions in animal models. The assessment of gene expression patterns in transplanted hAECs revealed that neuronal (Calca, Fox3) and oligodendrocyte (MBP) genes in the injured spinal cord of the animal models were upregulated. Histopathological analysis showed a reduction in inflammation and glial scar formation, while neural fiber regeneration increased in the treated animals. Also, DII labeled-hAECs in the lesion site were alive after a period of four weeks.ConclusionBased on these findings, it can be inferred that the integrative therapeutic effects of human amniotic epithelial cells, nanochitosan/polypyrrole-Alginate conductive scaffold, and Noggin (as BMP-4 signaling inhibitor) represents a promising and innovative approach in the field of translational medicine.

Project description:In clinical trials, new scaffolds for regeneration after spinal cord injury (SCI) should reflect the importance of a mechanically optimised, hydrated environment. Composite scaffolds of nonwovens, self-assembling peptides (SAPs) and hydrogels offer the ability to mimic native spinal cord tissue, promote aligned tissue regeneration and tailor mechanical properties. This work studies the effects of an aligned electrospun nonwoven of P11-8-enriched poly(ε-caprolactone) (PCL) fibres, integrated with a photo-crosslinked hydrogel of glycidylmethacrylated collagen (collagen-GMA), on neurite extension. Mechanical properties of collagen-GMA hydrogel in compression and shear were recorded, along with cell viability. Collagen-GMA hydrogels showed J-shaped stress-strain curves in compression, mimicking native spinal cord tissue. For hydrogels prepared with a 0.8-1.1 wt.% collagen-GMA concentration, strain at break values were 68 ± 1-81 ± 1% (±SE); maximum stress values were 128 ± 9-311 ± 18 kPa (±SE); and maximum force values were 1.0 ± 0.1-2.5 ± 0.1 N (±SE). These values closely mimicked the compression values for feline and porcine tissue in the literature, especially those for 0.8 wt.%. Complex shear modulus values fell in the range 345-2588 Pa, with the lower modulus hydrogels in the range optimal for neural cell survival and growth. Collagen-GMA hydrogel provided an environment for homogenous and three-dimensional cell encapsulation, and high cell viability of 84 ± 2%. Combination of the aligned PCL/P11-8 electrospun nonwoven and collagen-GMA hydrogel retained fibre alignment and pore structure, respectively, and promoted aligned neurite extension of PC12 cells. Thus, it is possible to conclude that scaffolds with mechanical properties that both closely mimic native spinal cord tissue and are optimal for neural cells can be produced, which also promote aligned tissue regeneration when the benefits of hydrogels and electrospun nonwovens are combined.

Dataset Information

Therapeutic Effect of Biomimetic Scaffold Loaded with Human Amniotic Epithelial Cell-Derived Neural-like Cells for Spinal Cord Injury.

Publications

Therapeutic Effect of Biomimetic Scaffold Loaded with Human Amniotic Epithelial Cell-Derived Neural-like Cells for Spinal Cord Injury.

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