Arkenbosch J H C, Becker M A J, Buskens C J, Witjes C, de Vries A C, van der Woude C J, Fuhler G, Wildenberg M E, van Ruler O
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology & Metabolism, Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Stem Cell Res. 2023 Mar;67:103039. doi: 10.1016/j.scr.2023.103039. Epub 2023 Feb 2.
New cell-based therapies are under investigation to improve perianal fistulizing Crohn's disease (pCD) healing. Autologous stromal vascular fraction combined with platelet-rich plasma (referred to as platelet-rich stroma [PRS]) is a new adipose-derived stromal therapy. The effect of Crohn's disease (CD) on adipose tissue, and adipose-derived therapies, is largely unknown. We characterized the cellular composition of subcutaneous lipoaspirate and PRS of pCD patients and non-Inflammatory Bowel Disease (IBD) controls.
Consecutive pCD patients (≥18 years) and non-IBD controls, who underwent liposuction for the purpose of autologous PRS therapy, were included (October 2020 and March 2021). Mechanically fractionated lipoaspirate and the combined PRS product were analyzed for cell surface marker expression using fluorescence-activated cell sorting analysis.
Twenty-three patients (37.8 [IQR 30.7-45.0] years; 9 [39.1 %] male; 11CD patients) were included. Similar total number of cells were found in CD and non-IBD lipoaspirate (CD 8.23 ± 1.6210 cells/mL versus non-IBD 12.20 ± 3.3910). Presence of stromal cells, endothelial like cells, immune cells, T-cells, myeloid cells and M2/M1 macrophage ratio were similar in CD and non-IBD lipoaspirate. In PRS samples, more cells/mL were seen in CD patients (P = 0.030). Myeloid cells were more abundant in CD PRS samples (P = 0.007), and appeared to have a higher regulatory M2/M1 ratio. Interdonor variation was observed between lipoaspirate and PRS samples.
The composition of CD and non-IBD lipoaspirate were found to be similar and interdonor variation was observed. However, PRS from CD patients showed more myeloid cells with a regulatory phenotype. Crohn's disease does not appear to alter the immunological composition of adipose-derived products.
新型细胞疗法正在研究中,以改善肛周瘘管型克罗恩病(pCD)的愈合情况。自体基质血管成分联合富血小板血浆(称为富血小板基质[PRS])是一种新型脂肪源性基质疗法。克罗恩病(CD)对脂肪组织及脂肪源性疗法的影响在很大程度上尚不清楚。我们对pCD患者和非炎症性肠病(IBD)对照者的皮下抽脂物及PRS的细胞组成进行了表征。
纳入了连续的pCD患者(≥18岁)和非IBD对照者,他们因自体PRS治疗目的而接受了抽脂手术(2020年10月至2021年3月)。使用荧光激活细胞分选分析对机械分离的抽脂物和联合的PRS产品进行细胞表面标志物表达分析。
共纳入23例患者(年龄37.8[四分位间距30.7 - 45.0]岁;男性9例[39.1%];11例CD患者)。CD患者和非IBD患者的抽脂物中细胞总数相似(CD患者为8.23±1.62×10⁶细胞/mL,非IBD患者为12.20±3.39×10⁶细胞/mL)。CD患者和非IBD患者的抽脂物中基质细胞、内皮样细胞、免疫细胞、T细胞、髓样细胞以及M2/M1巨噬细胞比例相似。在PRS样本中,CD患者每毫升的细胞数更多(P = 0.030)。CD患者的PRS样本中髓样细胞更丰富(P = 0.007),且似乎具有更高的调节性M2/M1比例。在抽脂物和PRS样本之间观察到供体间差异。
发现CD患者和非IBD患者的抽脂物组成相似,并观察到供体间差异。然而,CD患者的PRS显示出更多具有调节表型的髓样细胞。克罗恩病似乎并未改变脂肪源性产品的免疫组成。