Tissue-engineered fibrin scaffolds containing neural progenitors enhance functional recovery in a subacute model of SCI

Johnson, Philip J.; Tatara, Alexander M.; McCreedy, Dylan A.; Shiu, Alicia; Sakiyama‐Elbert, Shelly E.

doi:10.1039/c0sm00173b

Cited by 120 publications

(108 citation statements)

References 30 publications

(76 reference statements)

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“…The presence of undifferentiated and undesirable phenotypes remains problematic for stem-cell based clinical applications where a high quality population of one or even multiple desired cell types are needed. For example, Johnson et al [40] transplanted mESC-derived EBs along with fibrin scaffolds containing neurotrophic factors in a rat spinal cord injury model where these factors promoted cellular proliferation. When the fibrin scaffolds were functionalized with an affinity-based drug delivery system for the neurotrophic factors, even more proliferation was achieved.…”

Section: 24mentioning

confidence: 99%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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Induced pluripotent stem cells (iPSCs) are generated from adult somatic cells through the induction of key transcription factors that restore the ability to become any cell type found in the body. These cells are of interest for tissue engineering due to their potential for developing patient-specific therapies. As the technology for generating iPSCs advances, it is important to concurrently investigate protocols for the efficient differentiation of these cells to desired downstream phenotypes in combination with biomaterial scaffolds as a way of engineering neural tissue. For such applications, the generation of neurons within three dimensional fibrin scaffolds has been well characterized as a cell-delivery platform for murine embryonic stem cells (ESCs) but has not yet been applied to murine iPSCs. Given that iPSCs have been reported to differentiate less effectively than ESCs, a key objective of this investigation is to maximize the proportion of iPSC-derived neurons in fibrin through the choice of differentiation protocol. To this end, this study compares two EB-mediated protocols for generating neurons from murine iPSCs and ESCs: an 8-day 4-/4+ protocol using soluble retinoic acid in the last 4 days and a 6-day 2-/4+ protocol using soluble retinoic acid and the small molecule sonic hedgehog agonist purmorphamine in the last 4 days. EBs were then seeded in fibrin scaffolds for 14 days to allow further differentiation into neurons. EBs generated by the 2-/4+ protocol yielded a higher percentage of neurons compared to those from the 4-/4+ protocol for both iPSCs and ESCs. The results demonstrate the successful translation of the fibrin-based cell-delivery platform for use with murine iPSCs and furthermore that the proportion of neurons generated from murine iPSC-derived EBs seeded in fibrin can be maximized using the 2-/4+ differentiation protocol. Together, these findings validate the further exploration of 3D fibrin-based scaffolds as a method of delivering neuronal cells derived from iPSCs -an important step toward the development of iPSC-based tissue engineering strategies for spinal cord injury repair.

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Section: 24mentioning

confidence: 99%

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

et al. 2015

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“…A 3-D system involving an air-liquid interface was shown to generate a self-organized three-dimensional neural tissue guided by endogenous developmental cues on hydrophilic polytetrafluoroethylene membrane [81] . Tissue-engineered fibrin scaffolds were developed to enhance PSC-derived NPC survival and direct differentiation into neurons [82] . All these studies demonstrated that 3-D scaffolds physically influenced neural lineage commitment from PSCs.…”

Section: Differentiation Of Pscsmentioning

confidence: 99%

Neural differentiation from pluripotent stem cells: The role of natural and synthetic extracellular matrix

Liu

Yan

et al. 2014

WJSC

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Neural cells differentiated from pluripotent stem cells (PSCs), including both embryonic stem cells and induced pluripotent stem cells, provide a powerful tool for drug screening, disease modeling and regenerative medicine. High-purity oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) have been derived from PSCs recently due to the advancements in understanding the developmental signaling pathways. Extracellular matrices (ECM) have been shown to play important roles in regulating the survival, proliferation, and differentiation of neural cells. To improve the function and maturation of the derived neural cells from PSCs, understanding the effects of ECM over the course of neural differentiation of PSCs is critical. During neural differentiation of PSCs, the cells are sensitive to the properties of natural or synthetic ECMs, including biochemical composition, biomechanical properties, and structural/topographical features. This review summarizes recent advances in neural differentiation of human PSCs into OPCs and NPCs, focusing on the role of ECM in modulating the composition and function of the differentiated cells. Especially, the importance of using three-dimensional ECM scaffolds to simulate the in vivo microenvironment for neural differentiation of PSCs is highlighted. Future perspectives including the immediate applications of PSC-derived neural cells in drug screening and disease modeling are also discussed.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Pluripotent stem cells; Neural differentiation; Extracellular matrix; Three-dimensional; Drug screening Core tip: Neural cells derived from human pluripotent stem cells (hPSCs), including oligodendrocyte progenitor cells and neural progenitor cells, emerge as an unlimited and physiologically relevant cell source for drug screening, disease modeling, and regenerative medicine. Natural and synthetic extracellular matrices play an important role in regulating neural differentiation, cell migration, and the derived neural cell maturation. Recent advances in neural differentiation of hPSCs on extracellular matrices in 2-D and 3-D systems are reviewed in this paper. The immediate applications of the derived neural cells in drug screening and disease modeling are also discussed.

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“…For instance, Chacko et al studied the effect of hypoxia pretreatment on cell expression of functional proteins that may increase their survival and engraftment after transplantation [2]. Hydrogels have also been used as vehicles for cell transplantation in order to improve survival [3][4][5]. For instance, Johnson et al reported that fibrin scaffolds can enhance survival of neural stem/progenitors cells (NSPCs) in a sub-acute model of SCI [4].…”

Section: Introductionmentioning

confidence: 99%

Combining Adult Stem Cells and Olfactory Ensheathing Cells: The Secretome Effect

Silva

Gimble

Sousa

et al. 2013

Stem Cells and Development

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Adipose-derived adult stem cells (ASCs), bone marrow mesenchymal stem cells (bmMSCs), and human umbilical cord perivascular cells (HUCPVCs) tissue have been widely tested for regenerative applications, such as bone regeneration. Moreover, olfactory ensheathing cells (OECs) show promise in promoting spinal cord injury (SCI) regeneration. Our group recently proposed the use of a hybrid scaffold targeting both vertebral bone repair and SCI regeneration. According to this concept, both MSCs and OECs should be in close contact to be influenced by the factors that are involved in secretion. For this reason, here we studied the effects of the OEC secretome on the metabolic activity and proliferation of ASCs, bmMSCs, and HUCPVCs. The stem cells' secretome effects on metabolic activity and proliferation of the OECs were also considered. In co-cultures of OECs with ASCs, bmMSCs, or HUCPVCs, the metabolic activity/viability, proliferation, and total cell numbers were measured after 2 and 7 days of culture. The results demonstrated that the secretome of OECs has a positive effect on the metabolic activity and proliferation of MSCs from different origins, especially on ASCs. Furthermore, in general, the stem cells' secretome also had a positive effect on the OECs behavior, particularly when ASCs were in co-culture with OECs. These results suggest that the most suitable combination of cells to be used in our hybrid scaffold is the OECs with the ASCs. Finally, this work adds new knowledge to the cell therapy field, bringing new information about paracrine interactions between OECs and distinct mesenchymal stems.

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Tissue-engineered fibrin scaffolds containing neural progenitors enhance functional recovery in a subacute model of SCI

Cited by 120 publications

References 30 publications

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

Engineering personalized neural tissue by combining induced pluripotent stem cells with fibrin scaffolds

Neural differentiation from pluripotent stem cells: The role of natural and synthetic extracellular matrix

Combining Adult Stem Cells and Olfactory Ensheathing Cells: The Secretome Effect

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