Adipose stem cells enhance excisional wound healing in a porcine model

James, Isaac; Bourne, Debra; Silva, Mayara; Havis, Emmanuelle; Albright, Kassandra; Zhang, Liyong; Kostereva, Nataliya; Wang, Sheri; DiBernardo, Gabriella; Guest, Rachel; Lei, Jenny; Almadori, Aurora; Satish, Latha; Marra, Kacey G.; Rubin, J. Peter

doi:10.1016/j.jss.2018.03.068

Cited by 20 publications

(17 citation statements)

References 55 publications

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“…Based on our ndings, it seems reasonable to conclude that in a clinical context, it is important to pay attention to the concentrations of ASCs in fat grafts. A suitable concentration of ASCs could decrease brosis and increase long-term retention, whereas excessive ASCs could have the opposite effects [51,52]. Since ASCs can directly induce the phenotype of M2 macrophage, the transformation of macrophages may also affect the shifting process of CD4 + T-cells [6,53].…”

Section: Discussionmentioning

confidence: 99%

Adipose-derived stem cells regulate fibrosis by altering CD4+ T-cell immune responses in fat grafting in a mouse model

Chen

Wang

et al. 2020

Preprint

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Background Autologous fat grafting is becoming increasingly common worldly. However, the long-term retention of fat grafting is still unpredictable due to the inevitable fibrosis that arises during tissue repair. Fibrosis may be regulated by T-cell immune responses that are influenced by adipose-derived stem cells (ASCs). Accordingly, we hypothesized that overly abundant ASCs might promote fibrosis by promoting T-cell immune responses to adipose tissue. Methods We performed 0.3 ml fat grafts with 104/ml, 106/ml and 108/ml ASCs and control group in C57 BL/6 mice in vivo. We observed retention, fibrosis, T-cell immunity, and macrophage infiltration over 12 weeks. In addition, CD4 + T-helper 1 (Th1) cells and T-helper 2 (Th2) cells were co-cultured with ASCs or ASCs conditioned media (CM) in vitro. We detected the ratio of Th2%/Th1% after 24 and 48 hours. Results In vivo, the retention rate was higher in the 104 group, while even lower in the 108 group with significantly increased inflammation and fibrosis than the control group at week 12. There was no significance between control group and the 106 group. Also, the 108 group increased infiltration of M2 macrophages, CD4 + T-cells and Th2/Th1 ratio. In vitro, the ratio of Th2%/Th1% induced by the ASCs-transwell group was higher than the ASCs-CM group and showed concentration-dependent. Conclusions High concentrations of ASCs in adipose tissue can promote Th1–Th2 shifting, and the excess of Th2 cells might promote the persistence of M2 macrophages and increase the level of fibrosis which lead to a decrease in the long-term retention of fat grafts. In addition, we found that ASCs promoted Th1–Th2 shifting in vitro.

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Section: Discussionmentioning

confidence: 99%

Adipose-derived stem cells regulate fibrosis by altering CD4+ T-cell immune responses in fat grafting in a mouse model

Chen

Wang

et al. 2020

Preprint

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“…Among the different sources of MSCs, adipose tissue is perceived as an abundant and easily obtainable pool with the benefits of extensive distribution and minimally invasive extraction [4]. Adipose-derived mesenchymal stem cells (ADSCs), which are adipose-derived stromal cells originating from stromal-vascular fragments of adipose tissue, show promising therapeutic value because of their essential role in enhancing the injury repair of many tissues [5][6][7][8][9]. ADSCs are believed to promote tissue regeneration either directly, by differentiating into a variety of cell types, such as osteoblasts, chondrocytes, liver cells, and neuronal cells, or indirectly, via paracrine signaling, whereby secreted factors activate regenerative pathways in host tissues [10,11].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Exosomes from Adipose-Derived Mesenchymal Stem Cells: A Novel Therapeutic Strategy for Tissue Injury

Xing

Han

Cheng

et al. 2020

BioMed Research International

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Exosomes are extracellular membranous nanovesicles that mediate local and systemic cell-to-cell communication by transporting functional molecules, such as proteins, into target cells, thereby affecting the behavior of receptor cells. Exosomes originating from adipose-derived mesenchymal stem cells (ADSCs) are considered a multipotent and abundant therapeutic tool for tissue injury. To investigate ADSC-secreted exosomes and their potential function in tissue repair, we isolated exosomes from the supernatants of ADSCs via ultracentrifugation, characterized them via transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. Then, we determined their protein profile via proteomic analysis. Results showed that extracellular vesicles, which have an average diameter of 116 nm, exhibit a cup-shaped morphology and express exosomal markers. A total of 1,185 protein groups were identified in the exosomes. Gene Ontology analysis indicated that exosomal proteins are mostly derived from cells mainly involved in protein binding. Protein annotation via the Cluster of Orthologous Groups system indicated that most proteins were involved in general function prediction, posttranslational modification, protein turnover, and chaperoning. Further, pathway analysis revealed that most of the proteins obtained participated in metabolic pathways, focal adhesion, regulation of the actin cytoskeleton, and microbial metabolism. Some tissue repair-related signaling pathways were also discovered. The identified molecules might serve as potential therapeutic targets for future studies.

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“…In addition, hASCs are especially suitable for wound healing applications due to their ability to secrete a wide variety of paracrine factors related to wound healing and due to their differentiation capability [16,17]. In vivo, they have been shown to stimulate angiogenesis and to enhance wound closure [18,19]. However, obstacles exist for successful cell transplantation including poor survival and low retention of cells in a target tissue, which typically is caused by the accumulation of cells in other tissues or enzymatic digestion of the single-cell suspension after systemic or topical administration [20,21].…”

Section: Introductionmentioning

confidence: 99%

Nanofibrillar cellulose wound dressing supports the growth and characteristics of human mesenchymal stem/stromal cells without cell adhesion coatings

et al. 2019

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Background: In the field of regenerative medicine, delivery of human adipose-derived mesenchymal stem/stromal cells (hASCs) has shown great promise to promote wound healing. However, a hostile environment of the injured tissue has shown considerably to limit the survival rate of the transplanted cells, and thus, to improve the cell survival and retention towards successful cell transplantation, an optimal cell scaffold is required. The objective of this study was to evaluate the potential use of wood-derived nanofibrillar cellulose (NFC) wound dressing as a cell scaffold material for hASCs in order to develop a cell transplantation method free from animal-derived components for wound treatment. Methods: Patient-derived hASCs were cultured on NFC wound dressing without cell adhesion coatings. Cell characteristics, including cell viability, morphology, cytoskeletal structure, proliferation potency, and mesenchymal cell and differentiation marker expression, were analyzed using cell viability assays, electron microscopy, immunocytochemistry, and quantitative or reverse transcriptase PCR. Student's t test and one-way ANOVA followed by a Tukey honestly significant difference post hoc test were used to determine statistical significance.Results: hASCs were able to adhere to NFC dressing and maintained high cell survival without cell adhesion coatings with a cell density-dependent manner for the studied period of 2 weeks. In addition, NFC dressing did not induce any remarkable cytotoxicity towards hASCs or alter the morphology, proliferation potency, filamentous actin structure, the expression of mesenchymal vimentin and extracellular matrix (ECM) proteins collagen I and fibronectin, or the undifferentiated state of hASCs.Conclusions: As a result, NFC wound dressing offers a functional cell culture platform for hASCs to be used further for in vivo wound healing studies in the future.

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Adipose stem cells enhance excisional wound healing in a porcine model

Cited by 20 publications

References 55 publications

Adipose-derived stem cells regulate fibrosis by altering CD4+ T-cell immune responses in fat grafting in a mouse model

Adipose-derived stem cells regulate fibrosis by altering CD4+ T-cell immune responses in fat grafting in a mouse model

Proteomic Analysis of Exosomes from Adipose-Derived Mesenchymal Stem Cells: A Novel Therapeutic Strategy for Tissue Injury

Nanofibrillar cellulose wound dressing supports the growth and characteristics of human mesenchymal stem/stromal cells without cell adhesion coatings

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