Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2+ macrophages.
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ABSTRACT:
SUBMITTER: Henn D
PROVIDER: S-EPMC8635426 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:1) We analyzed the impact of vitamind D3 (cholecalciferol) treatment on transcriptional signatures of bone marrow derived macrophages 2) Moreover, we analyzed cell populations infiltrating human split-thickness skin grafts (STSG) that had been subcutaneously implanted into wild-type mice (C57BL6/J).
2021-07-09 | GSE179745 | GEO
Project description:Xenogeneic Skin Transplantation Promotes Angiogenesis and Tissue Regeneration
| PRJNA744901 | ENA
Project description:Successful regenerative medicine strategies of xenogeneic extracellular matrix need a synergistic balance among inflammation, fibrosis, and remodeling process. Adaptive macrophage subsets have been identified to modulate inflammation and orchestrate the repair of neighboring parenchymal tissues. This study fabricated PPARγ-primed CD68+CD206+ M2 phenotype (M2γ), and firstly verified their anti-inflammatory and tissue-regenerating roles in xenogeneic bioengineered organ regeneration. Our results showed that Th1-type CD3+CD8+ T cell response to xenogeneic-dentin matrix-based bioengineered root complex (xeno-complex) was significantly inhibited by M2γ macrophage in vitro. PPARγ activation also timely recruited CD68+CD206+ tissue macrophage polarization to xeno-complex in vivo. These subsets alleviated proinflammatory cytokines (TNF-α, IFN-γ) at the inflammation site and decreased CD3+CD8+ T lymphocytes in the periphery system. When translated to an orthotopic nonhuman primate model, PPARγ-primed M2 macrophages immunosuppressed IL-1β, IL-6, TNF-α, MMPs to enable xeno-complex to effectively escape immune-mediated rejection and initiate graft-host synergistic integrity. These collective activities promoted the differentiation of odontoblast-like and periodontal-like cells to guide pulp-dentin and cementum-PDLs-bone regeneration and rescued partially injured odontogenesis such as DSPP and periostin expression. Finally, the regenerated root showed structure-biomechanical and functional equivalency to the native tooth. The timely conversion of M1-to-M2 macrophage mainly orchestrated odontogenesis, fibrogenesis, and osteogenesis, which represents a potential modulator for intact parenchymal-stromal tissue regeneration of targeted organs.
| S-EPMC7567936 | biostudies-literature
Project description:BackgroundTissue expansion is a procedure that promotes skin regeneration by mechanical stretch. During the stress and relaxation cycle, the skin undergoes a repeated microtrauma which triggers an immune response leading to the recruitment of macrophages to repair the damaged tissue. Macrophages have been found to be necessary for tissue repair and wound healing, but their effects on skin regeneration during mechanical stretch remain unclear.MethodsThe dynamic changes of macrophages in the rat skin tissues undergoing expansion were quantitatively determined by immunohistochemistry staining. The area of the expanded skin, skin thickness, dermal collagen density, cell proliferation and tissue vascularization were examined to determine the effects of macrophages on the expanding skin. The phenotypes of macrophages and the growth factors related to skin regeneration were also examined to evaluate the underlying mechanisms for the involvement of macrophages in skin regeneration. As a comparison, the tissue samples of expanding skin in which the macrophages were depleted by topically utilizing clodronate liposomes were also evaluated.ResultsThe number of skin macrophages in skin maintained in the high level during the skin expansion compared to non-expanded skin. We found that a switch from an M1- to M2-dominant response during tissue expansion. After the macrophages were depleted, the skin regeneration was inhibited, as evidenced by a smaller expansion area, thinner skin layers and decreased cell proliferation rate, collagen synthesis and, skin vascularization. The secretion of epidermal growth factor (EGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) were decreased when macrophages were depleted.ConclusionsOur findings suggest that macrophages are necessary for skin regeneration during tissue expansion. Modulating inflammation may provide a key therapeutic strategy to promote skin growth under mechanical strain.
| S-EPMC6341552 | biostudies-literature
Project description:The insufficient number of cells suitable for transplantation is a long-standing problem to cell-based therapies aimed at tissue regeneration. Xenogeneic cancer cells (XCC) may be an alternative source of therapeutic cells, but their transplantation risks both immune rejection and unwanted spreading. In this study, a strategy to facilitate XCC transplantation is reported and their spreading in vivo is confined by constructing an engineering matrix that mimics the characteristics of tumor microenvironment. The data show that this matrix, a tumor homogenate-containing hydrogel (THAG), successfully creates an immunosuppressive enclave after transplantation into immunocompetent mice. XCC of different species and tissue origins seeded into THAG survive well, integrated with the host and developed the intrinsic morphology of the native tissue, without being eliminated or spreading out of the enclave. Most strikingly, immortalized human hepatocyte cells and rat ?-cells loaded into THAG exert the physiological functions of the human liver and rat pancreas islets, respectively, in the mouse body. This study demonstrates a novel and feasible approach to harness the unique features of tumor development for tissue transplantation and regenerative medicine.
| S-EPMC5867037 | biostudies-other
Project description:Extracellular matrix (ECM)-based bioinks has attracted much attention in recent years for 3D printing of native-like tissue constructs. Due to organ unavailability, human placental ECM can be an alternative source for the construction of 3D print composite scaffolds for the treatment of deep wounds. In this study, we use different concentrations (1.5%, 3% and 5%w/v) of ECM derived from the placenta, sodium-alginate and gelatin to prepare a printable bioink biomimicking natural skin. The printed hydrogels' morphology, physical structure, mechanical behavior, biocompatibility, and angiogenic property are investigated. The optimized ECM (5%w/v) 3D printed scaffold is applied on full-thickness wounds created in a mouse model. Due to their unique native-like structure, the ECM-based scaffolds provide a non-cytotoxic microenvironment for cell adhesion, infiltration, angiogenesis, and proliferation. In contrast, they do not show any sign of immune response to the host. Notably, the biodegradation, swelling rate, mechanical property, cell adhesion and angiogenesis properties increase with the increase of ECM concentrations in the construct. The ECM 3D printed scaffold implanted into deep wounds increases granulation tissue formation, angiogenesis, and re-epithelialization due to the presence of ECM components in the construct, when compared with printed scaffold with no ECM and no treatment wound. Overall, our findings demonstrate that the 5% ECM 3D scaffold supports the best deep wound regeneration in vivo, produces a skin replacement with a cellular structure comparable to native skin.
| S-EPMC10239019 | biostudies-literature
Project description:Recently, attention has been focused on the central role of TREM2 in diverse pathologies. However, the role of TREM2 signaling in the tumor microenvironment of hepatocellular carcinoma (HCC) remains poorly understood. Herein, we systematically investigated the single-cell transcriptomes of human HCC tissues and found that TREM2 was predominantly expressed by a macrophage subpopulation enriched in tumor tissues that resemble lipid-associated macrophages (LAMs). The accumulation of TREM2+ LAM-like cells in HCC was confirmed in two additional cohorts using scRNA-seq analysis and immunohistochemistry. High expression of TREM2 correlated with high infiltrating macrophage abundance and poor prognosis. Based on systematic interrogations of transcriptional profiles and cellular interactions, TREM2+ LAM-like cells were identified to mainly originate from S100A8 + monocytes and represented an immunosuppressive state. TREM2+ LAM-like cells recruited suppressive Treg cells, facilitating microenvironment remodeling. Furthermore, gene regulatory analysis and in vitro functional assays indicated that activation of LXR signaling could promote the reprogramming of TREM2 + LAM-like cells. Correlation analysis of bulk RNA-sequencing data demonstrated that the enrichment of TREM2 + LAM-like cells was an independent indicator of adverse clinical outcomes in HCC patients. Our comprehensive analyses provide deeper insights into the immunosuppressive role of TREM2+ LAM-like cells in HCC.
| S-EPMC8963870 | biostudies-literature
Project description:Gametogenesis requires close interactions between germ cells and somatic cells. Derivation of sperm from spermatogonial stem cells (SSCs) is hampered by the inefficiency of spermatogonial transplantation technique in many animal species because it requires a large number of SSCs and depletion of endogenous spermatogenesis. Here we used mouse testis primordia and organoids to induce spermatogenesis from SSCs. We microinjected mouse SSCs into embryonic gonads or reaggregated neonatal testis organoids, which were transplanted under the tunica albuginea of mature testes. As few as 1 × 104 donor cells colonized both types of transplants and produced sperm. Moreover, rat embryonic gonads supported xenogeneic spermatogenesis from mouse SSCs when transplanted in testes of immunodeficient mice. Offspring with normal genomic imprinting patterns were born after microinsemination. These results demonstrate remarkable flexibility of the germ cell-somatic cell interaction and raise new strategies of SSC manipulation for animal transgenesis and analysis of male infertility.
| S-EPMC9023780 | biostudies-literature
Project description:Rationale: Systemic sclerosis (SSc) is a chronic and incurable autoimmune disease with high mortality rates, and skin fibrosis is one of distinguishing hallmarks in the pathogenesis. However, macrophage heterogeneity regulating skin fibrosis remain largely unknown. Methods: We established mouse disease model and performed single-cell RNA-sequencing (scRNA-seq) to resolve the dynamic and heterogenous characteristics of macrophages in skin fibrosis, and the role of TREM2-dependent macrophages in the pathological process was investigated using knockout mice and intraperitoneal transferring TREM2+ macrophages combining with functional assays. Results: We show that TREM2-expressing macrophages (TREM2+ MФs) accumulate in injured skin of mice treated by bleomycin (BLM) and human SSc, and their gene signatures and functional pathways are identified in the course of disease. Genetic ablation of Trem2 in mice globally accelerates and aggravates skin fibrosis, whereas transferring TREM2hi macrophages improves and alleviates skin fibrosis. Amazingly, we found that disease-associated TREM2+ MФs in skin fibrosis exhibit overlapping signatures with fetal skin counterparts in mice and human to maintain skin homeostasis, but each has merits in skin remodeling and development respectively. Conclusion: This study identifies that TREM2 acts as a functional molecule and a major signaling by which macrophage subpopulations play a protective role against fibrosis, and disease-associated TREM2+ MФs in skin fibrosis might undergo a fetal-like reprogramming similar to fetal skin counterparts.
| S-EPMC10945340 | biostudies-literature
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.
| S-EPMC6425411 | biostudies-literature