Dataset Information

Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2⁺ macrophages.

ABSTRACT: Skin allo- and xenotransplantation are the standard treatment for major burns when donor sites for autografts are not available. The relationship between the immune response to foreign grafts and their impact on wound healing has not been fully elucidated. Here, we investigated changes in collagen architecture after xenogeneic implantation of human biologic scaffolds. We show that collagen deposition in response to the implantation of human split-thickness skin grafts (hSTSGs) containing live cells recapitulates normal skin architecture, whereas human acellular dermal matrix (ADM) grafts led to a fibrotic collagen deposition. We show that macrophage differentiation in response to hSTSG implantation is driven toward regenerative Trem2⁺ subpopulations and found that hydrogel delivery of these cells significantly accelerated wound closure. Our study identifies the preclinical therapeutic potential of Trem2⁺ macrophages to mitigate fibrosis and promote wound healing, providing a novel effective strategy to develop advanced cell therapies for complex wounds.

SUBMITTER: Henn D

PROVIDER: S-EPMC8635426 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2<sup>+</sup> macrophages.

Henn Dominic D Chen Kellen K Fehlmann Tobias T Trotsyuk Artem A AA Sivaraj Dharshan D Maan Zeshaan N ZN Bonham Clark A CA Barrera Janos A JA Mays Chyna J CJ Greco Autumn H AH Moortgat Illouz Sylvia E SE Lin John Qian JQ Steele Sydney R SR Foster Deshka S DS Padmanabhan Jagannath J Momeni Arash A Nguyen Dung D Wan Derrick C DC Kneser Ulrich U Januszyk Michael M Keller Andreas A Longaker Michael T MT Gurtner Geoffrey C GC

Science advances 20211201 49

Skin allo- and xenotransplantation are the standard treatment for major burns when donor sites for autografts are not available. The relationship between the immune response to foreign grafts and their impact on wound healing has not been fully elucidated. Here, we investigated changes in collagen architecture after xenogeneic implantation of human biologic scaffolds. We show that collagen deposition in response to the implantation of human split-thickness skin grafts (hSTSGs) containing live ce ...[more]

PMID: 34851663

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Project description:Background and aimLipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this project are to investigate blood vasculature, immune cells, and structure of lipedema tissue in a cohort of women.MethodsForty-nine participants, 19 controls and 30 with lipedema, were divided into groups based on body mass index (BMI): Non-Obese (BMI 20 to <30 kg/m2) and Obese (BMI 30 to <40 kg/m2). Histological sections from thigh skin and fat were stained with H&E. Adipocyte area and blood vessel size and number were quantified using ImageJ software. Markers for macrophages (CD68), mast cells (CD117), T cells (CD3), endothelial cells (CD31), blood (SMA), and lymphatic (D2-40 and Lyve-1) vessels were investigated by IHC and IF.ResultsNon-Obese Lipedema adipocyte area was larger than Non-Obese Controls (p=0.005) and similar to Obese Lipedema and Obese Controls. Macrophage numbers were significantly increased in Non-Obese (p < 0.005) and Obese (p < 0.05) Lipedema skin and fat compared to Control groups. No differences in T lymphocytes or mast cells were observed when comparing Lipedema to Control in both groups. SMA staining revealed increased dermal vessels in Non-Obese Lipedema patients (p < 0.001) compared to Non-Obese Controls. Lyve-1 and D2-40 staining showed a significant increase in lymphatic vessel area but not in number or perimeter in Obese Lipedema participants (p < 0.05) compared to Controls (Obese and Non-Obese). Areas of angiogenesis were found in the fat in 30% of lipedema participants but not controls.ConclusionHypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh tissue of non-obese women with lipedema suggest inflammation, and angiogenesis occurs independent of obesity and demonstrates a role of altered vasculature in the manifestation of the disease.

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Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2⁺ macrophages.

Publications

Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2<sup>+</sup> macrophages.

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Dataset Information

Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2+ macrophages.

Publications

Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2<sup>+</sup> macrophages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2⁺ macrophages.