Fibrin hydrogels induce mixed dorsal/ventral spinal neuron identities during differentiation of human induced pluripotent stem cells

Edgar, John M.; Robinson, Meghan; Willerth, Stephanie M.

doi:10.1016/j.actbio.2017.01.040

Cited by 43 publications

(27 citation statements)

References 72 publications

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“…The low expression of SSEA‐4 indicates the mature differentiation of the cell aggregates into neural tissues. The quantitative analysis of SOX‐2 (another pluripotency marker) at this stage showed (3.62 ± 1.65%) of total cells in the aggregates treated with M, (3.17 ± 2.21%) of cell aggregates with U, (4.09 ± 2.16%) for N, and (16.56 ± 0.34%) in the P. The high expression for P could be attributed to a neuronal precursor state, whereas similar lower levels of expression in the other groups can be attributed to a more pluripotent state on day 15 …”

Section: Discussionmentioning

confidence: 85%

Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres

2018

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Here a novel technique for engineering neural tissue consisting of motor neurons by combining human‐induced pluripotent stem cells (hiPSCs) with small molecules releasing microspheres is demonstrated. First, the small molecule purmorphamine (puro) is successfully encapsulated into poly ε‐caprolactone (PCL) microspheres using a single emulsion oil‐in‐water (o/w) method for the first time with an efficiency of (84% ± 2.12%). These microspheres release 91% ± 1.7% of the encapsulated puro in a controlled fashion over 46 days. Puro microspheres, along with previously characterized retinoic acid (RA) releasing microspheres, are then incorporated into hiPSC aggregates to engineer neural tissue. The combination of puro and RA microspheres promotes hiPSC differentiation as indicated by the expression of multiple neural markers, including the neuronal marker β‐tubulin III (βT‐III), and the transcription factor Olig2 (7.69 ± 8.38%) on day 28. These tissues express the motor neuron marker HB9 (24.85 ± 4.51%) on day 35, and the mature motor neuron marker ChaT (12.35 ± 4.17%) on day 60. These engineered tissues can be used for regenerative medicine applications such as treating spinal cord injury (SCI), disease modeling, and drug screening.

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Section: Discussionmentioning

confidence: 85%

Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres

2018

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“…The results of this work showed that the partially differentiated iPSC‐RPE can directly adhere to the fibrin gel, form a monolayer and express phenotype specific marker proteins . Similarly, work from Willerths' group has demonstrated culture of iPSC‐derived neural aggregates on fibrin hydrogels can be used to generate a mixed population of dorsal and ventral spinal neurons . These examples highlight the ability to differentiate iPSC‐derived progenitor‐type populations to terminally differentiated cells using fibrin hydrogels.…”

Section: Introductionmentioning

confidence: 69%

Human Fibrinogen for Maintenance and Differentiation of Induced Pluripotent Stem Cells in Two Dimensions and Three Dimensions

Gandhi

Knudsen

Hill

et al. 2019

Stem Cells Translational Medicine

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Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)‐derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three‐dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture. iPSCs successfully adhered to and proliferated on fibrin hydrogels. The two‐dimensional culture with fibrinogen allows for immediate adaption of culture models to a nonxenogeneic model. Similarly, multiple commercially available iPSC lines adhered to and proliferated on fibrinogen coated surfaces. iPSCs cultured on fibrinogen expressed similar levels of the pluripotent stem cell markers SSea4 (98.7% ± 1.8%), Oct3/4 (97.3% ± 3.8%), TRA1‐60 (92.2% ± 5.3%), and NANOG (96.0% ± 3.9%) compared with iPSCs on Geltrex. Using a trilineage differentiation assay, we found no difference in the ability of iPSCs grown on fibrinogen or Geltrex to differentiate to endoderm, mesoderm, or ectoderm. Finally, we demonstrated the ability to differentiate iPSCs to endothelial cells using only fibrinogen coated plates. On the basis of these data, we conclude that human fibrinogen provides a readily available and inexpensive alternative to laminin‐based products for the growth, expansion, and differentiation of iPSCs for use in research and clinical cell therapy applications. stem cells translational medicine 2019;8:512–521

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“…Bioactive scaffolds, including 3D printed devices, multifunctional electrospun scaffolds, and drug releasing microspheres have been used to promote differentiation of pluripotent stem cells into neural tissues [54][55][56][57][58][59][60][61][62]. In particular, novel 3D printed fibrin formulations produced by the Willerth Lab have been shown to promote mouse and human induced pluripotent stem cell differentiations to form neural tissues that consist of different neuronal phenotypes [54,55,60,61]. As shown in Figure 3, the researchers use genipin to crosslink fibrin matrix in order to increase the resulting fibrin scaffold stability while decreasing the degradation rate of fibrin.…”

Section: D Bioprinted Bioactive Biomaterialsmentioning

confidence: 99%

Advancements in Canadian Biomaterials Research in Neurotraumatic Diagnosis and Therapies

Chen

Auriat

et al. 2019

Processes

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Development of biomaterials for the diagnosis and treatment of neurotraumatic ailments has been significantly advanced with our deepened knowledge of the pathophysiology of neurotrauma. Canadian research in the fields of biomaterial-based contrast agents, non-invasive axonal tracing, non-invasive scaffold imaging, scaffold patterning, 3D printed scaffolds, and drug delivery are conquering barriers to patient diagnosis and treatment for traumatic injuries to the nervous system. This review highlights some of the highly interdisciplinary Canadian research in biomaterials with a focus on neurotrauma applications.

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Fibrin hydrogels induce mixed dorsal/ventral spinal neuron identities during differentiation of human induced pluripotent stem cells

Cited by 43 publications

References 72 publications

Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres

Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres

Human Fibrinogen for Maintenance and Differentiation of Induced Pluripotent Stem Cells in Two Dimensions and Three Dimensions

Advancements in Canadian Biomaterials Research in Neurotraumatic Diagnosis and Therapies

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