经肛直肠环肌间肛瘘治疗中无应答者和应答者脂肪间充质干细胞的分子差异。
Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas.
机构信息
Molecular Endocrinology and Stem Cell Research Unit, Department of Endocrinology and Metabolism, Odense University Hospital and Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Molecular Physiology of Bone, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic.
出版信息
Stem Cell Res Ther. 2021 Nov 24;12(1):586. doi: 10.1186/s13287-021-02644-8.
BACKGROUND
Injection of autologous adipose tissue (AT) has recently been demonstrated to be an effective and safe treatment for anal fistulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fistula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process.
METHODS
27 patients (age 45 ± 2 years) diagnosed with perianal fistula were enrolled in the study and treated with autologous AT injected around the anal fistula tract. AT-MSCs were isolated for cellular and molecular analyses. The fistula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fistula healing.
RESULTS
52% of all patients exhibited clinical healing of the fistulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast differentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte differentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of inflammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1.
CONCLUSION
Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, differentiation capacity and secretion of proinflammatory molecules may provide a possible mechanism underlying fistula healing. Furthermore, these biomarkers may be useful to predict a positive fistula healing outcome.
TRIAL REGISTRATION
NTC04834609, Registered 6 April 2021. https://clinicaltrials.gov/ct2/show/NCT04834609.
背景
自体脂肪组织（AT）注射最近已被证明是治疗肛瘘的有效且安全的方法。脂肪间充质干细胞（AT-MSCs）介导愈合过程，但注射 AT 中 AT-MSCs 的分子特征与瘘管愈合之间的关系尚未得到充分研究。因此，我们旨在表征从自体注射 AT 中分离的 AT-MSCs 的分子和功能特性，将这些发现与愈合过程相关联。
方法
研究纳入了 27 名（年龄 45±2 岁）诊断为肛门瘘的患者，并接受了自体 AT 注射治疗。对 AT-MSCs 进行细胞和分子分析。在治疗 6 个月后，通过 MRI 扫描评估瘘管愈合情况。根据瘘管愈合情况，比较了 responder 和 non-responder 患者的 AT-MSC 表型。
结果
52%的患者在最后一次注射后 6 个月评估时表现出瘘管的临床愈合。在 responder 组中，与 non-responder AT-MSCs 相比，培养的 AT-MSCs 具有较低的短期增殖率和较高的成骨细胞分化潜能。另一方面，non-responder 组的脂肪细胞分化潜能更高。有趣的是，responder 组的 AT-MSCs 表现出较低的炎症和衰老相关基因（如 IL1B、NFKB、CDKN2A、TPB3、TGFB1）的表达。
结论
我们的数据表明，注射的 AT-MSCs 的细胞质量，包括细胞增殖、分化能力和促炎分子的分泌，可能为瘘管愈合提供了一种潜在的机制。此外，这些生物标志物可能有助于预测瘘管愈合的积极结果。
试验注册
NTC04834609，注册于 2021 年 4 月 6 日。https://clinicaltrials.gov/ct2/show/NCT04834609。
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