Neural stem cell delivery via porous collagen scaffolds promotes neuronal differentiation and locomotion recovery in spinal cord injury

Kourgiantaki, Alexandra; Tzeranis, Dimitrios S.; Karali, Kanelina; Georgelou, Konstantina; Bampoula, Efstathia; Psilodimitrakopoulos, Sotirios; Yannas, Ioannis V.; Stratakis, Emmanuel; Sidiropoulou, Kyriaki; Charalampopoulos, Ioannis; Gravanis, Achille

doi:10.1038/s41536-020-0097-0

Cited by 74 publications

(48 citation statements)

References 46 publications

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“…On the other hand, scaffolds made from biocompatible materials may provide structural support for cell adhesion, proliferation, and differentiation mimicking the cellular microenvironment. A number of scaffolds made from solid [ 3 , 4 , 5 ], microfibrous materials [ 6 ], or gels [ 7 ] have been previously described to support the proliferation and localized differentiation of murine neural stem cells, indicating their potential value for neural tissue regeneration [ 8 ]. Among them, 3D foam biomaterials provide efficient cell adhesion, proliferation, and differentiation due to their unique properties (e.g., high surface-to-volume ratio, 3D porous structure) [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility of α-Al2O3 Ceramic Substrates with Human Neural Precursor Cells

Asimakopoulou

Gkekas

Kastrinaki

et al. 2020

JFB

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Background: Biocompatible materials-topography could be used for the construction of scaffolds allowing the three-dimensional (3D) organization of human stem cells into functional tissue-like structures with a defined architecture. Methods: Structural characterization of an alumina-based substrate was performed through XRD, Brunauer–Emmett–Teller (BET) analysis, scanning electron microscopy (SEM), and wettability measurements. Biocompatibility of the substrate was assessed by measuring the proliferation and differentiation of human neural precursor stem cells (NPCs). Results: α-Al2O3 is a ceramic material with crystallite size of 40 nm; its surface consists of aggregates in the range of 8–22 μm which forms a rough surface in the microscale with 1–8 μm cavities. The non-calcined material has a surface area of 5.5 m2/gr and pore size distribution of 20 nm, which is eliminated in the calcined structure. Thus, the pore network on the surface and the body of the ceramic becomes more water proof, as indicated by wettability measurements. The alumina-based substrate supported the proliferation of human NPCs and their differentiation into functional neurons. Conclusions: Our work indicates the potential use of alumina for the construction of 3D engineered biosystems utilizing human neurons. Such systems may be useful for diagnostic purposes, drug testing, or biotechnological applications.

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Section: Introductionmentioning

confidence: 99%

Biocompatibility of α-Al2O3 Ceramic Substrates with Human Neural Precursor Cells

Asimakopoulou

Gkekas

Kastrinaki

et al. 2020

JFB

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“…Mature neurons display myelin-based inhibition of neurite outgrowth in vitro [ 9 ]. If Mbp is essential to myelin-induced neurite outgrowth, Mbp overexpression may rescue myelin-based inhibition of neurite outgrowth in mature NPCs.…”

Section: Resultsmentioning

confidence: 99%

Myelin basic protein enhances axonal regeneration from neural progenitor cells

et al. 2021

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Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.

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“…By contrast, the composite strategies integrating cells, bioactive molecules, and biomaterials have thus attracted significant interest over the past few years to improve cell survival, reduce side effects across the blood-brain barrier, and achieve local delivery. For example, implantation of porous collagen-based scaffolds (PCSs) seeded with neural stem cells can enhance cell delivery and differentiation, activate robust axonal elongation, and decrease astrogliosis in animals [ 290 ]. HA is an extensively considered and modified natural polymer for a regenerative scaffold of CNS because it plays an important role in neural tissues by regulating cell migration, proliferation, and differentiation.…”

Section: Chronic Inflammation-associated Diseases and Therapiesmentioning

confidence: 99%

The Dynamic Inflammatory Tissue Microenvironment: Signality and Disease Therapy by Biomaterials

et al. 2021

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Tissue regeneration is an active multiplex process involving the dynamic inflammatory microenvironment. Under a normal physiological framework, inflammation is necessary for the systematic immunity including tissue repair and regeneration as well as returning to homeostasis. Inflammatory cellular response and metabolic mechanisms play key roles in the well-orchestrated tissue regeneration. If this response is dysregulated, it becomes chronic, which in turn causes progressive fibrosis, improper repair, and autoimmune disorders, ultimately leading to organ failure and death. Therefore, understanding of the complex inflammatory multiple player responses and their cellular metabolisms facilitates the latest insights and brings novel therapeutic methods for early diseases and modern health challenges. This review discusses the recent advances in molecular interactions of immune cells, controlled shift of pro- to anti-inflammation, reparative inflammatory metabolisms in tissue regeneration, controlling of an unfavorable microenvironment, dysregulated inflammatory diseases, and emerging therapeutic strategies including the use of biomaterials, which expand therapeutic views and briefly denote important gaps that are still prevailing.

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Neural stem cell delivery via porous collagen scaffolds promotes neuronal differentiation and locomotion recovery in spinal cord injury

Cited by 74 publications

References 46 publications

Biocompatibility of α-Al2O3 Ceramic Substrates with Human Neural Precursor Cells

Biocompatibility of α-Al2O3 Ceramic Substrates with Human Neural Precursor Cells

Myelin basic protein enhances axonal regeneration from neural progenitor cells

The Dynamic Inflammatory Tissue Microenvironment: Signality and Disease Therapy by Biomaterials

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