Gelatin-based 3D conduits for transdifferentiation of mesenchymal stem cells into Schwann cell-like phenotypes

Uz, Metin; Büyüköz, Melda; Sharma, Anup D.; Sakaguchi, Donald S.; Altınkaya, Sacide Alsoy; Mallapragada, Surya K.

doi:10.1016/j.actbio.2017.02.018

Cited by 42 publications

(54 citation statements)

References 129 publications

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“…The ability of these cells to differentiate into neurons, astrocytes, and oligodendrocytes, the principal neural cell types of the CNS, provides an advantage for studying directed cell differentiation . Combined with biomaterials, scaffolds can also influence cell differentiation thus promoting stem cells into neural lineages for therapeutic strategies for nervous system rescue and repair . However, little is known about the extent to which PCL microfibers may impact cell proliferation and directed cell differentiation.…”

Section: Introductionsupporting

confidence: 80%

3D Microfibrous Scaffolds Selectively Promotes Proliferation and Glial Differentiation of Adult Neural Stem Cells: A Platform to Tune Cellular Behavior in Neural Tissue Engineering

Patel

Sharifi

Stroud

et al. 2018

Macromolecular Bioscience

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Biomaterials are essential for the development of innovative biomedical and therapeutic applications. Biomaterials‐based scaffolds can influence directed cell differentiation to improve cell‐based strategies. Using a novel microfluidics approach, poly (ε‐caprolactone) (PCL), is used to fabricate microfibers with varying diameters (3–40 µm) and topographies (straight and wavy). Multipotent adult rat hippocampal stem/progenitor cells (AHPCs) are cultured on 3D aligned PCL microfibrous scaffolds to investigate their ability to differentiate into neurons, astrocytes, and oligodendrocytes. The results indicate that the PCL microfibers significantly enhance proliferation of the AHPCs compared to control, 2D planar substrates. While the AHPCs maintained their multipotent differentiation capacity when cultured on the PCL scaffolds, there is a significant and dramatic increase in immunolabeling for astrocyte and oligodendrocyte differentiation when compared with growth on planar surfaces. Our results show a 3.5‐fold increase in proliferation and 23.4‐fold increase in astrocyte differentiation for cells on microfibers. Transplantation of neural stem/progenitor cells within a PCL microfiber scaffold may provide important biological and topographic cues that facilitate the survival, selective differentiation, and integration of transplanted cells to improve therapeutic strategies.

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Section: Introductionsupporting

confidence: 80%

3D Microfibrous Scaffolds Selectively Promotes Proliferation and Glial Differentiation of Adult Neural Stem Cells: A Platform to Tune Cellular Behavior in Neural Tissue Engineering

Patel

Sharifi

Stroud

et al. 2018

Macromolecular Bioscience

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“…In addition, this was also found to be considerably higher than the NGF secretion obtained in our previous studies, which varied between 0.5 to 2.5 pg/mL per cell. 23,24 Therefore, the synergistic effect of 3D microstructural and mechanical properties and electrical stimuli did not cause significant measurable improvements in the degree of differentiation; however, it significantly enhanced the paracrine activity. To further demonstrate the biological activity of the secreted NGF, we conducted a non-contact co-culture experiment with PC12-TrkB cells.…”

Section: Cellular Growth and Differentiation Of Mscs In The Conduit/smentioning

confidence: 95%

“…The obtained gelatin-graphene conduits were cross-linked using 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide HCl (EDC) and N-hydroxy-succinimide (NHS) chemistry. 23…”

Section: Preparation Of Gelatin Conduits With Graphene Rodsmentioning

confidence: 99%

Development of Gelatin and Graphene-Based Nerve Regeneration Conduits Using Three-Dimensional (3D) Printing Strategies for Electrical Transdifferentiation of Mesenchymal Stem Cells

Donta

Mededovic

et al. 2019

Ind. Eng. Chem. Res.

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In this study, gelatin and graphene-based nerve regeneration conduits/scaffolds possessing tailored 3D microstructures and mechanical properties were fabricated using 3D printing. The effect of 3D conduit microstructure and mechanical properties along with the applied electrical stimuli on mesenchymal stem cell (MSCs) behavior and transdifferentiation into Schwann cell (SC)-like phenotypes were investigated. The results indicated that the gelatin conduits/scaffolds had favorable 3D microstructural and mechanical properties for MSC attachment and growth. Immunocytochemistry results demonstrated that the application of electrical stimuli through the conductive graphene within the gelatin-based 3D microstructure had a profound effect on the differentiation of MSCs to SC-like phenotypes and their paracrine activity. 80% of the cells exhibited SC marker staining, and the cells showed significantly enhanced nerve growth factor (NGF) secretion. These results suggest that the electrical stimuli applied within the 3D gelatin matrix enables enhanced differentiation and paracrine activity compared to transdifferentiation procedures involving electrical stimuli applied on 2D substrates and chemical stimuli applied in 3D gelatin scaffolds, leading to promising nerve regeneration strategies.

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“…44 Therefore, the degree of secreted neurotrophic factors can be considered another measure of cell differentiation. 45 As such, NGF, BDNF, and VEGF expressed by hUCMSCs cultured within different PLGA films for 7 and 14 days were assessed by qRT-PCR (Fig. 7).…”

Section: Cell Proliferation and Morphology On Dopa-igf-1@plga Filmsmentioning

confidence: 99%

A Novel Approach via Surface Modification of Degradable Polymers With Adhesive DOPA-IGF-1 for Neural Tissue Engineering

Zhang

Wang

et al. 2019

Journal of Pharmaceutical Sciences

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The highly damaging state of spinal cord injuries has provided much inspiration for the design of surface modification of the implants that can promote nerve regeneration and functional reconstruction. DOPA-IGF-1, a new recombinant protein designed in our previous study, exhibited strong binding affinity to titanium and significantly enhanced the growth of NIH3T3 cells on the surface of titanium with the same biological activity as IGF-1. In this article, surface modification of poly(lactide-co-glycolide) (PLGA) films with recombinant DOPA-IGF-1 was performed to promote the paracrine activity of human umbilical cord mesenchymal stem cells (hUCMSCs) by secreting neurotrophic factors. DOPA-IGF-1 exhibited the strongest binding ability to PLGA films than commercial IGF-1 and nonhydroxylated YKYKY-IGF-1. In vitro cultures of hUCMSCs on the modified PLGA films showed that DOPA-IGF-1@PLGA substrates significantly improved the proliferation, adhesion, and neurotrophic factors secretion of hUCMSCs, especially for nerve growth factor, as confirmed by qRT-PCR and western blot analysis. Subsequently, the acquired neurotrophic factors secreted by the hUCMSCs cultured on the DOPA-IGF-1@PLGA films obviously enhanced neurite outgrowth of PC12 cells. Taken together, PLGA substrates with DOPA-IGF-1 immobilization is a promising platform for neural tissue engineering via neurotrophic factors secretion from MSCs and should be further tested in vivo.

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Gelatin-based 3D conduits for transdifferentiation of mesenchymal stem cells into Schwann cell-like phenotypes

Cited by 42 publications

References 129 publications

3D Microfibrous Scaffolds Selectively Promotes Proliferation and Glial Differentiation of Adult Neural Stem Cells: A Platform to Tune Cellular Behavior in Neural Tissue Engineering

3D Microfibrous Scaffolds Selectively Promotes Proliferation and Glial Differentiation of Adult Neural Stem Cells: A Platform to Tune Cellular Behavior in Neural Tissue Engineering

Development of Gelatin and Graphene-Based Nerve Regeneration Conduits Using Three-Dimensional (3D) Printing Strategies for Electrical Transdifferentiation of Mesenchymal Stem Cells

A Novel Approach via Surface Modification of Degradable Polymers With Adhesive DOPA-IGF-1 for Neural Tissue Engineering

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