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Preconditioning Human Adipose-Derived Stromal Cells on Decellularized Adipose Tissue Scaffolds Within a Perfusion Bioreactor Modulates Cell Phenotype and Promotes a Pro-regenerative Host Response.

ABSTRACT: Cell-based therapies involving the delivery of adipose-derived stromal cells (ASCs) on decellularized adipose tissue (DAT) scaffolds are a promising approach for soft tissue augmentation and reconstruction. Our lab has recently shown that culturing human ASCs on DAT scaffolds within a perfusion bioreactor prior to implantation can enhance their capacity to stimulate in vivo adipose tissue regeneration. Building from this previous work, the current study investigated the effects of bioreactor preconditioning on the ASC phenotype and secretory profile in vitro, as well as host cell recruitment following implantation in an athymic nude mouse model. Immunohistochemical analyses indicated that culturing within the bioreactor increased the percentage of ASCs co-expressing inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1), as well as tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10), within the peripheral regions of the DAT relative to statically cultured controls. In addition, bioreactor culture altered the expression levels of a range of immunomodulatory factors in the ASC-seeded DAT. In vivo testing revealed that culturing the ASCs on the DAT within the perfusion bioreactor prior to implantation enhanced the infiltration of host CD31⁺ endothelial cells and CD26⁺ cells into the DAT implants, but did not alter CD45⁺F4/80⁺CD68⁺ macrophage recruitment. However, a higher fraction of the CD45⁺ cell population expressed the pro-regenerative macrophage marker CD163 in the bioreactor group, which may have contributed to enhanced remodeling of the scaffolds into host-derived adipose tissue. Overall, the findings support that bioreactor preconditioning can augment the capacity of human ASCs to stimulate regeneration through paracrine-mediated mechanisms.

SUBMITTER: Han TTY

PROVIDER: S-EPMC8012684 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Stem cell expansion on 3D porous scaffolds cultured in bioreactor systems has been shown to be beneficial for maintenance of the original cell functionality in tissue engineering strategies (TE). However, the production of extracellular matrix (ECM) makes harvesting the progenitor cell population from 3D scaffolds a challenge. Medium composition plays a role in stimulating cell proliferation over extracellular matrix (ECM) production. In this regard, a computational model describing tissue growth inside 3D scaffolds can be a great tool in designing optimal experimental conditions. In this study, a computational model describing cell and ECM growth in a perfusion bioreactor is developed, including a description of the effect of a (generic) growth factor on the biological processes taking place inside the 3D scaffold. In the model, the speed of cell and ECM growth depends on the flow-induced shear stress, curvature and the concentrations of oxygen, glucose, lactate, and growth factor. The effect of the simulated growth factor is to differentially enhance cell proliferation over ECM production. After model calibration with historic in-house data, a multi-objective optimization procedure is executed aiming to minimize the total experimental cost whilst maximizing cell growth during culture. The obtained results indicate there are multiple optimum points for the medium refreshment regime and the initial growth factor concentration where a trade-off is made between the final amount of cells and the culture cost. Finally, the model is applied to experiments reported in the literature studying the effects of perfusion-based cell culture and/or growth factor supplementation on cell expansion. The qualitative similarities between the simulation and experimental results, even in the absence of proper model calibration, reinforces the generic character of the proposed modeling framework. The model proposed in this study can contribute to the cost efficient production of cell-based TE products, ultimately contributing to their affordability and accessibility.

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Preconditioning Human Adipose-Derived Stromal Cells on Decellularized Adipose Tissue Scaffolds Within a Perfusion Bioreactor Modulates Cell Phenotype and Promotes a Pro-regenerative Host Response.

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