Adipose Stromal Cells Enhance Decellularized Adipose Tissue Remodeling Through Multimodal Mechanisms

Robb, Kevin P.; Juignet, Laura; Martin, Pascal Morissette; Walker, John T.; Brooks, Courtney; Barreira, Christy; Dekaban, Gregory A.; Flynn, Lauren E.

doi:10.1089/ten.tea.2020.0180

Cited by 14 publications

(13 citation statements)

References 57 publications

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“…In particular, CD163 + macrophages have been associated with both angiogenesis and ECM remodeling in implanted biomaterials ( Spiller et al, 2014 ). The increased presence of CD163 + macrophages within the dynamically cultured implants is similar to our previous findings on the effects of ASC seeding in the immunocompetent rat and mouse models ( Han et al, 2015 ; Robb et al, 2020 ), and these cells may have contributed to the enhanced remodeling of the DAT into host-derived adipose tissue ( Han and Flynn, 2020 ).…”

Section: Discussionsupporting

confidence: 87%

“…As such, the effects of dynamic culture on host macrophage recruitment were probed through co-staining for CD45, F4/80, and CD68, which showed no significant differences in terms of cell densities between the groups at any of the timepoints. Similarly, we previously found that seeding with ASCs modulated macrophage phenotype but did not specifically alter macrophage recruitment into the DAT implants in immunocompetent rat and mouse models ( Han et al, 2015 ; Robb et al, 2020 ). Notably, there was an increased percentage of CD45 + cells that were F4/80 – and CD68 – within both implant groups at 8 weeks.…”

Section: Discussionmentioning

confidence: 57%

“…This strategy may be critical for the larger volume augmentation that is required for many reconstructive applications in the clinic, as a lack of angiogenesis and host cell infiltration can result in implant failure. Previous work from our lab supports that seeding the DAT with adipose-derived stromal cells (ASCs) can enhance in vivo angiogenesis and host adipogenesis in immunocompetent mouse and rat models (Han et al, 2015;Robb et al, 2020). ASCs are a logical cell source for this application given their relative abundance and accessibility (Bourin et al, 2013), their high tolerance of ischemic conditions such as those immediately following implantation (Suga et al, 2010), as well as their enhanced adipogenic potential compared to other mesenchymal stromal cell (MSC) sources (Pizzute et al, 2015).…”

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confidence: 86%

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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

Han

Walker

Grant

et al. 2021

Front. Bioeng. Biotechnol.

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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.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 57%

mentioning

confidence: 86%

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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

Han

Walker

Grant

et al. 2021

Front. Bioeng. Biotechnol.

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“…The cryosectioned samples were rinsed and then blocked for 1 h at RT with TBS supplemented with 10% goat serum and 1% TWEEN ® 20. The samples were then stained overnight at 4 C using anti-rabbit primary antibodies for Iba1 to identify host macrophages 29 (Abcam, ab178846, diluted 1:200) or CD31 to identify host endothelial cells (Abcam, ab28364, diluted 1:300). No primary antibody controls were included in all trials.…”

Section: In Vivo Characterizationmentioning

confidence: 99%

Development and characterization of matrix‐derived microcarriers from decellularized tissues using electrospraying techniques

Kornmuller

Flynn

2021

J Biomedical Materials Res

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Stirred bioreactor systems integrating microcarriers represent a promising approach for therapeutic cell manufacturing. While a variety of microcarriers are commercially available, current options do not integrate the tissue-specific composition of the extracellular matrix (ECM), which can play critical roles in directing cell function. The current study sought to generate microcarriers comprised exclusively of ECM from multiple tissue sources. More specifically, porcine decellularized dermis, porcine dec-

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“…The extracellular matrix plays an important role in modulating various cell behaviors including adhesion, proliferation and differentiation 10 . Decellularized adipose tissues have been used extensively as a promising scaffold material which provide a 3D complex ECM architecture for adipogenesis 11‐14 . Multiple strategies involving both synthetic and natural materials have been developed for soft tissue reconstruction 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Hybrid adipose graft materials synthesized from chemically modified adipose extracellular matrix

Liu

McCann

et al. 2021

J Biomedical Materials Res

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Decellularized extracellular matrix (ECM) from tissues is a promising biomaterial that can provide a complex 3D microenvironment capable of modulating cell response and tissue regeneration. In this study, we have integrated the decellularized thiolated adipose‐derived ECM, at different concentrations, with polyethylene glycol (PEG) using Michael addition between thiol and acrylate moieties. The potential for this material to support adipogenic differentiation of human adipose‐derived stem cells was evaluated by encapsulating cells in hydrogels with increasing concentrations of chemically modified ECM (mECM). Our results demonstrated a positive correlation between the ECM content in the hydrogels and cell proliferation, adipogenic marker expression, and lipid formation and accumulation. Furthermore, we have shown host cell infiltration and enhanced adipogenesis in vivo after implantation. These findings support the graft as a potential alternative for adipose tissue regeneration.

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Adipose Stromal Cells Enhance Decellularized Adipose Tissue Remodeling Through Multimodal Mechanisms

Cited by 14 publications

References 57 publications

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

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

Development and characterization of matrix‐derived microcarriers from decellularized tissues using electrospraying techniques

Hybrid adipose graft materials synthesized from chemically modified adipose extracellular matrix

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