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Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

ABSTRACT: Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates.

SUBMITTER: Song MJ

PROVIDER: S-EPMC4216563 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

Song Min Jae MJ Dean David D Knothe Tate Melissa L ML

Biomaterials 20130507 23

Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially r ...[more]

PMID: 23660249

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Project description:Treatment strategies of critical nerve injuries involving nerve gaps more than 3 cm are still not optimal. The need for an alternative to the standard autologous nerve grafts has led to the exploration of adipose derived stem cells (ASC) seeded in bioartificial nerve conduits for enhancement of peripheral nerve regeneration. ASC can be differentiated into Schwann cell like cells, which is believed to improve their neurotrophic potency. Nevertheless, the differentiation process requires several weeks and there is no evidence that the cells maintain their differentiated phenotype in vivo. Thus, the present study evaluated the synergistic effect of undifferentiated ASC with exogenously added growth factors in vitro with the aim to improve the neurotrophic potency of undifferentiated ASC through short ex-vivo stimulation with growth factors. The study furthermore provides a comparative in vitro assay of the six well-known neurotrophic factors NGF, GDNF, BDNF, CNTF, NT3 and NT4. ASC were cultured and thus stimulated in the presence of the respective exogenous growth factor for three days and resulting conditioned medium was evaluated in an in vitro axonal outgrowth assay. In addition, also unstimulated ASC’s conditioned medium was tested in combination with the respective exogenous growth factor for the same assay, which was perfomed on dorsal root ganglion (DRG) explants from 10 days old embryonic chicken. DRG explants from most promising conditions were further analyzed for upregulated STAT-3 and GAP-43 by qRT-PCR. Furthermore, also proteomics and phosphoproteomics were performed for ASC and DRG explants using mass spectrometry. The quantity of selected proteins contained in the ASC’s conditioned medium was investigated by ELISA. Combination of ASC’s conditioned medium with growth factors generally resulted in significantly enhanced axonal outgrowth when compared with their control of DRG explants cultured with the respective growth factor only. Specifically, conditioned medium derived from NT3-stimulated as well as ASC’s conditioned medium supplemented with NT3 or BDNF elicited significant axonal outgrowth from DRG explants in contrast to all other experimental conditions. Significant upregulation of STAT-3 and GAP-43 was evidenced for DRG explants grown in NT3-stimulated ASC’s conditioned medium and to a certain extent also for DRG cultured in ASC’s conditioned medium supplemented with NT3.

Dataset Information

Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

Publications

Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

Similar Datasets

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