Adipose-Derived Mesenchymal Stem Cells Attenuate Immune Reactions Against Pig Decellularized Bronchi Engrafted into Rat Tracheal Defects.

IF 1.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Organogenesis Pub Date : 2023-12-31 DOI:10.1080/15476278.2023.2212582

Makoto Hisanaga, Tomoshi Tsuchiya, Hironosuke Watanabe, Koichiro Shimoyama, Mayumi Iwatake, Yukinori Tanoue, Keizaburo Maruyama, Hiroshi Yukawa, Kazuhide Sato, Yoshimi Kato, Keitaro Matsumoto, Takuro Miyazaki, Ryoichiro Doi, Koichi Tomoshige, Takeshi Nagayasu

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引用次数: 1

Abstract

Decellularized scaffolds are promising biomaterials for tissue and organ reconstruction; however, strategies to effectively suppress the host immune responses toward these implants, particularly those without chemical crosslinking, remain warranted. Administration of mesenchymal stem cells is effective against immune-mediated inflammatory disorders. Herein, we investigated the effect of isogeneic abdominal adipose-derived mesenchymal stem/stromal cells (ADMSCs) on xenogeneic biomaterial-induced immunoreactions. Peripheral bronchi from pigs, decellularized using a detergent enzymatic method, were engrafted onto tracheal defects of Brown Norway (BN) rats. BN rats were implanted with native pig bronchi (Xenograft group), decellularized pig bronchi (Decellularized Xenograft), or Decellularized Xenograft and ADMSCs (Decellularized Xenograft+ADMSC group). In the latter group, ADMSCs were injected intravenously immediately post implantation. Harvested graft implants were assessed histologically and immunohistochemically. We found that acute rejections were milder in the Decellularized Xenograft and Decellularized Xenograft+ADMSC groups than in the Xenograft group. Mild inflammatory cell infiltration and reduced collagen deposition were observed in the Decellularized Xenograft+ADMSC group. Additionally, ADMSC administration decreased CD8+ lymphocyte counts but increased CD163+ cell counts. In the Decellularized Xenograft+ADMSC group, serum levels of vascular endothelial growth factor and IL-10 were elevated and tissue deposition of IgM and IgG was low. The significant immunosuppressive effects of ADMSCs illustrate their potential use as immunosuppressive agents for xenogeneic biomaterial-based implants.

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脂肪源性间充质干细胞减弱猪脱细胞支气管移植大鼠气管缺损的免疫反应。

脱细胞支架是用于组织和器官重建的有前途的生物材料；然而，有效抑制宿主对这些植入物的免疫反应的策略，特别是那些没有化学交联的植入物，仍然是有必要的。间充质干细胞的给药对免疫介导的炎症性疾病是有效的。在此，我们研究了同种异体腹部脂肪来源的间充质干细胞/基质细胞（ADMSC）对异种生物材料诱导的免疫反应的影响。使用洗涤剂酶法脱细胞的猪外周支气管移植到Brown Norway（BN）大鼠的气管缺损上。BN大鼠植入天然猪支气管（异种移植物组）、脱细胞猪支气管（脱细胞异种移植物）或脱细胞异种移植和ADMSC（脱细胞异体移植物+ADMSC组）。在后一组中，ADMSC在植入后立即静脉注射。对采集的移植物植入物进行组织学和免疫组织化学评估。我们发现，脱细胞异种移植物和脱细胞异种移植+ADMSC组的急性排斥反应比异种移植物组轻。脱细胞异种移植物+ADMSC组观察到轻度炎症细胞浸润和胶原沉积减少。此外，ADMSC给药降低了CD8+淋巴细胞计数，但增加了CD163+细胞计数。在脱细胞异种移植物+ADMSC组中，血清血管内皮生长因子和IL-10水平升高，IgM和IgG的组织沉积较低。ADMSC的显著免疫抑制作用说明了它们作为基于异种生物材料的植入物的免疫抑制剂的潜在用途。

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来源期刊

Organogenesis BIOCHEMISTRY & MOLECULAR BIOLOGY-DEVELOPMENTAL BIOLOGY

CiteScore

4.10

自引率

4.30%

发文量

审稿时长

>12 weeks

期刊介绍： Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes. The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering. The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.