Single-cell mass cytometry reveals in vivo immunological response to surgical biomaterials

Wu, Haoyu; Han, Shan; Wu, Bowen; Du, Xiaotian; Sheng, Zhaohan; Lin, Junxin; Chen, Xuri; Zhao, Kun; Bunpetch, Varitsara; Chen, Yishan; Zeng, Mengfeng; Alakpa, Enateri V.; Ma, Yihua; Lei, Xiaoyue; Huang, Jichao; Zou, Xiaohui; Ouyang, Hongwei

doi:10.1016/j.apmt.2019.05.007

Cited by 18 publications

(20 citation statements)

References 37 publications

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“…An overview of different immune cells in the microenvironment will aid in the comprehensive understanding of the immune responses elicited by scaffolds. Technological advances, such as single-cell RNA sequencing (scRNA-seq) ( 14 , 15 ), have enabled cell population, cell function, and the nuances of their phenotypes in vivo to be studied at a high resolution. By changing the collector, we developed poly(lactic- co -glycolic acid)–fish collagen (PLGA-FC) hybrid electrospun scaffolds with three types of surface topography, i.e., groups with randomly oriented fibers (random group), mesh-like topography and randomly oriented fibers in microscale (latticed group), and aligned fibers (aligned group).…”

Section: Introductionmentioning

confidence: 99%

Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

Chu

Liu

et al. 2021

Sci. Adv.

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The structural properties of biomaterials play crucial roles in guiding cell behavior and influencing immune responses against the material. We fabricated electrospun membranes with three types of surface topography (random, aligned, and latticed), introduced them to dorsal skin excisional wounds in mice and rats, and evaluated their effects on wound healing and immunomodulatory properties. An overview of different immune cells in the microenvironment with the help of single-cell RNA sequencing revealed diverse cellular heterogeneity in vivo. The time course of immune response was advanced toward an adaptive immunity–dominant stage by the aligned scaffold. In mice without mature T lymphocytes, lack of wound-induced hair neogenesis indicated a regulatory role of T cells on hair follicle regeneration. The microenvironment around scaffolds involved an intricate interplay of immune and cutaneous cells.

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Section: Introductionmentioning

confidence: 99%

Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

Chu

Liu

et al. 2021

Sci. Adv.

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“…An overview of different immune cells in the microenvironment will aid in comprehensive understanding of the immune responses elicited by scaffolds. Technological advances such as single-cell RNA sequencing (scRNA-seq) (18,19) have significantly advanced the knowledge of the immune system. (20) Heterogeneity of cell populations, functions, and the nuances of their phenotypes in vivo can be revealed at a high resolution.…”

Section: Introductionmentioning

confidence: 99%

“…An overview of different immune cells in the microenvironment will aid in comprehensive understanding of the immune responses elicited by scaffolds. Technological advances such as single-cell RNA sequencing (scRNA-seq) (13, 14) have enabled cell populations, functions, and the nuances of their phenotypes in vivo to be studied at a high resolution. By changing the collector, we developed poly(lactic-co-glycolic acid)-fish collagen (PLGA-FC) hybrid electrospun scaffolds with three types of surface topography, i.e.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

Hu¹,

Chu²,

Liu

et al. 2020

Preprint

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Structural properties of biomaterials play critical roles in guiding cell behaviors and influence the immune response against them. In this study, we fabricated electro-spun membranes with three types of surface topography (Random, Aligned, and Latticed). The aligned membranes showed immunomodulatory ability, and led to faster wound healing, reduced fibrotic response and enhanced regeneration of cutaneous appendages. Based on that, we performed single-cell RNA sequencing analysis on cells of wounded mouse skin in the presence/absence of the Aligned scaffold. We identified 45 cell populations. Keratinocytes, fibroblasts, and immune cells including neutrophils, monocytes, macrophages, dendritic cells, and T cells showed diverse cellular heterogeneity. We found more inner root sheath cells (anagen-related) in the Aligned group, which corresponded to the improved regeneration of hair follicles in the presence of scaffold. The immune microenvironment around the biomaterial involved intricate interplay of immune cells from both innate and adaptive immune system. Immune responses in tissue around scaffold significantly differed from that of saline control. In aligned samples, infiltrated macrophages and neutrophils were reduced, whereas more effector T cells were recruited. The time course of immune response might be advanced towards an adaptive immunity-dominant stage by scaffolds.

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“…Decreased expression of IL-1β was found when cells were cultured on aligned PCL scaffold, as compared to those cultured on random PCL scaffold [34] . Wu et al compared the immune responses of two biomaterials (silk and polypropylene) after implantation and found that silk induced less recruitment of neutrophils and macrophages, less fibrosis formation, and better tissue healing [35] . In our current study, the biomimetic silk scaffold with aligned structure significantly increased the expression of anti-inflammatory phenotype marker CD206, as compared to the random silk scaffold (Fig.…”

Section: Discussionmentioning

confidence: 99%

The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration

Chen

Sheng

et al. 2021

Stem Cell Res Ther

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Background With the development of tissue engineering, enhanced tendon regeneration could be achieved by exploiting suitable cell types and biomaterials. The accessibility, robust cell amplification ability, superior tendon differentiation potential, and immunomodulatory effects of human periodontal ligament stem cells (hPDLSCs) indicate their potential as ideal seed cells for tendon tissue engineering. Nevertheless, there are currently no reports of using PDLSCs as seed cells. Previous studies have confirmed the potential of silk scaffold for tendon tissue engineering. However, the biomimetic silk scaffold with tendon extracellular matrix (ECM)-like structure has not been systematically studied for in situ tendon regeneration. Therefore, this study aims to evaluate the effects of hPDLSCs and biomimetic silk scaffold on in situ tendon regeneration. Methods Human PDLSCs were isolated from extracted wisdom teeth. The differentiation potential of hPDLSCs towards osteo-, chondro-, and adipo-lineage was examined by cultured in different inducing media. Aligned and random silk scaffolds were fabricated by the controlled directional freezing technique. Scaffolds were characterized including surface structure, water contact angle, swelling ratio, degradation speed and mechanical properties. The biocompatibility of silk scaffolds was evaluated by live/dead staining, SEM observation, cell proliferation determination and immunofluorescent staining of deposited collagen type I. Subsequently, hPDLSCs were seeded on the aligned silk scaffold and transplanted into the ruptured rat Achilles tendon. Scaffolds without cells served as control groups. After 4 weeks, histology evaluation was carried out and macrophage polarization was examined to check the repair effects and immunomodulatory effects. Results Human PDLSCs were successfully isolated, and their multi-differentiation potential was confirmed. Compared with random scaffold, aligned silk scaffold had more elongated and aligned pores and promoted the proliferation and ordered arrangement of hPDLSCs. After implantation into rat Achilles tendon defect, hPDLSCs seeded aligned silk scaffold enhanced tendon repair with more tendon-like tissue formation after 4 weeks, as compared to the scaffold-only groups. Higher expression of CD206 and lower expression of iNOS, IL-1β and TNF-α were found in the hPDLSCs seeded aligned silk scaffold group, which revealed its modulation effect of macrophage polarization from M1 to M2 phenotype. Conclusions In summary, this study demonstrates the efficacy of hPDLSCs as seed cells and aligned silk scaffold as a tendon-mimetic scaffold for enhanced tendon tissue engineering, which may have broad implications for future tendon tissue engineering and regenerative medicine researches.

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Single-cell mass cytometry reveals in vivo immunological response to surgical biomaterials

Cited by 18 publications

References 37 publications

Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

The application of human periodontal ligament stem cells and biomimetic silk scaffold for in situ tendon regeneration

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