Application of adipose-derived stem cells in treating fibrosis

Li, Zhu-Jun; Wang, Liquan; Li, Yun-Zhu; Wang, Chenyu; Huang, Jiuzuo; Yu, Nanze; Long, Xiao

doi:10.4252/wjsc.v13.i11.1747

Cited by 8 publications

(6 citation statements)

References 65 publications

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“…On day 14 after implantation, the harvested tissues from the two ADSC-laden groups showed a well-organized epidermal structure and a well-distributed dermal structure with clear vascular and fibrous tissues and minimal inflammatory cell infiltration. We speculate that the limited inflammatory infiltration may be related to modulation of neutrophil, macrophage, and lymphocyte responses by MSC-secreted growth factors and cytokines [ 53 ] . In comparison, the epidermis was fractured in samples from the two groups treated with acellular scaffolds, and fibrous tissue hyperplasia was found in the dermis, especially in the GelMA–HAMA group.…”

Section: Resultsmentioning

confidence: 99%

3D-bioprinted human lipoaspirate-derived cellladen skin constructs for healing of full-thickness skin defects

Zhang¹,

Fu²,

Fu³

et al. 2024

IJB

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Three-dimensional (3D)-printed bioactive scaffolds that can be produced rapidly could offer an individualized approach for treating full-thickness skin defects. Decellularized extracellular matrix (dECM) and mesenchymal stem cells have been proven to support wound healing. Adipose tissues obtained by liposuction are rich in adipose-derived dECM (adECM) and adipose-derived stem cells (ADSCs) and thus represent a natural source of bioactive materials for 3D bioprinting. Herein, ADSC-laden 3D-printed bioactive scaffolds consisting of gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), and adECM were fabricated with dual properties of photocrosslinking in vitro and thermosensitive crosslinking in vivo. adECM was prepared by decellularization of human lipoaspirate and mixed as a bioactive material with GelMA and HAMA to form a bioink. Compared with the GelMA–HAMA bioink, the adECM–GelMA–HAMA bioink had better wettability, degradability, and cytocompatibility. Full-thickness skin defect healing in a nude mouse model showed that ADSC-laden adECM–GelMA–HAMA scaffolds accelerated wound healing by promoting faster neovascularization, collagen secretion, and remodeling. ADSCs and adECM collectively conferred bioactivity on the prepared bioink. This study represents a novel approach to enhancing the biological activity of 3D-bioprinted skin substitutes by adding adECM and ADSCs derived from human lipoaspirate and may provide a promising therapeutic option for full-thickness skin defects.

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Section: Resultsmentioning

confidence: 99%

3D-bioprinted human lipoaspirate-derived cellladen skin constructs for healing of full-thickness skin defects

Zhang¹,

Fu²,

Fu³

et al. 2024

IJB

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“…In addition, N-cadherin-transfected ASCs promote angiogenesis and cardiomyocyte differentiation, thereby reducing ventricular fibrosis and increasing the ejection fraction in a mouse model of ischemic heart disease [ 38 ]. Anti-fibrotic effects of ASCs have been repeatedly reported in the lungs, kidneys, and skin [ 17 , 18 , 39 ]. Based on these studies, inhibition of the TGFβ/Smad signaling axis, paracrine effects by various growth factors released from ASCs, anti-oxidative effects, and anti-inflammatory effects have been suggested as mechanisms by which ASCs suppress fibrosis [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Anti-fibrotic effects of ASCs have been repeatedly reported in the lungs, kidneys, and skin [ 17 , 18 , 39 ]. Based on these studies, inhibition of the TGFβ/Smad signaling axis, paracrine effects by various growth factors released from ASCs, anti-oxidative effects, and anti-inflammatory effects have been suggested as mechanisms by which ASCs suppress fibrosis [ 39 ]. In this study, we found that the mRNA levels of TGFβ, a master regulator of fibrosis that governs the production of extracellular matrix, and molecules operating downstream of TGFβ, were decreased in ASC-treated peri-implant capsules.…”

Section: Discussionmentioning

confidence: 99%

Implantation and tracing of green fluorescent protein-expressing adipose-derived stem cells in peri-implant capsular fibrosis

Park

Kwon

et al. 2023

Stem Cell Res Ther

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Background Adipose-derived stem cells (ASCs) have been reported to reduce fibrosis in various tissues. In this study, we investigated the inhibitory role of ASCs on capsule formation by analyzing the histologic, cellular, and molecular changes in a mouse model of peri-implant fibrosis. We also investigated the fate and distribution of ASCs in the peri-implant capsule. Methods To establish a peri-implant fibrosis model, customized silicone implants were inserted into the dorsal site of C57BL/6 wild-type mice. ASCs were harvested from the fat tissues of transgenic mice that express a green fluorescent protein (GFP-ASCs) and then injected into the peri-implant space of recipient mice. The peri-implant tissues were harvested from postoperative week 2 to 8. We measured the capsule thickness, distribution, and differentiation of GFP-ASCs, as well as the cellular and molecular changes in capsular tissue following ASC treatment. Results Injected GFP-ASCs were distributed within the peri-implant capsule and proliferated. Administration of ASCs reduced the capsule thickness, decreased the number of myofibroblasts and macrophages in the capsule, and decreased the mRNA level of fibrogenic genes within the peri-implant tissue. Angiogenesis was enhanced due to trans-differentiation of ASCs into vascular endothelial cells, and tissue hypoxia was relieved upon ASC treatment. Conclusions We uncovered that implanted ASCs inhibit capsule formation around the implant by characterizing a series of biological alterations upon ASC treatment and the fate of injected ASCs. These findings highlight the value of ASCs for future clinical applications in the prevention of capsular contracture after implant-based reconstruction surgery.

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“…To the best of our knowledge, there are no previous reports on short exposition (4h) of cells in vitro to TGF-β1, others tried concentrations from 0.1 to 10 ng/ml for longer periods (24h; Li et al. 2021 ; Qin et al. 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles secreted by equine adipose mesenchymal stem cells preconditioned with transforming growth factor β-1 are enriched in anti-fibrotic miRNAs and inhibit the expression of fibrotic genes in an in vitro system of endometrial stromal cells fibrosis

Wong,

Mançanares,

Navarrete

et al. 2024

Veterinary Quarterly

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Mare endometrosis is a major reproductive problem associated with low fertility and is characterized by persistent inflammation, TGFβ-1 signaling, and consequently, extracellular matrix deposition, which compromises endometrial glands. Mesenchymal stem cell-based products (MSCs), such as extracellular vesicles (EVs), have gained attention due to the regulatory effects exerted by their miRNA cargo. Here, we evaluated the impact of preconditioning equine adipose mesenchymal stem cells with TGFβ-1 for short or long periods on the anti-fibrotic properties of secreted extracellular vesicles. MSCs were isolated from six healthy horses and exposed to TGFβ-1 for 4, 24, and 0 h. The expression of anti-fibrotic and pro-fibrotic miRNAs and mRNAs in treated cells and miRNAs in the cargo of secreted extracellular vesicles was measured. The resulting EVs were added for 48 h to endometrial stromal cells previously induced to a fibrotic status. The expression of anti-fibrotic and pro-fibrotic genes and miRNAs was evaluated in said cells using qPCR and next-generation sequencing. Preconditioning MSCs with TGFβ-1 for 4 h enriched the anti-fibrotic miRNAs (mir29c, mir145, and mir200) in cells and EVs. Conversely, preconditioning the cells for 24 h leads to a pro-fibrotic phenotype overexpressing mir192 and mir433. This finding might have implications for developing an EV-based protocol to treat endometrial fibrosis in mares.

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Application of adipose-derived stem cells in treating fibrosis

Cited by 8 publications

References 65 publications

3D-bioprinted human lipoaspirate-derived cellladen skin constructs for healing of full-thickness skin defects

3D-bioprinted human lipoaspirate-derived cellladen skin constructs for healing of full-thickness skin defects

Implantation and tracing of green fluorescent protein-expressing adipose-derived stem cells in peri-implant capsular fibrosis

Extracellular vesicles secreted by equine adipose mesenchymal stem cells preconditioned with transforming growth factor β-1 are enriched in anti-fibrotic miRNAs and inhibit the expression of fibrotic genes in an in vitro system of endometrial stromal cells fibrosis

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