Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
Inflamm Bowel Dis. 2018 Jul 12;24(8):1755-1767. doi: 10.1093/ibd/izy130.
Mesenchymal stromal cells (MSCs) are a potential therapeutic modality in inflammatory bowel diseases (IBDs) because of their immunomodulatory and regenerative properties. However, when injected systemically, only a small portion of the cells, if any, reach the inflamed colon. In this study, we assessed whether endoscopic injections of MSCs into the intestinal wall of the inflamed colon affect the course of experimental colitis. Furthermore, we investigated if injection of aggregated MSCs in spheroids could enhance their therapeutic ability.
Expression levels of in vivo MSC aggregates and in vitro MSC spheroids were compared with monolayer cultured MSCs for both anti-inflammatory and pro-regenerative factors. Subsequently, MSCs and MSC spheroids were injected endoscopically in mice with established dextran sulfate sodium (DSS)-induced colitis.
Endoscopically injected MSCs and MSC spheroids both alleviated DSS-induced colitis. Furthermore, both in vivo and in vitro MSC spheroids showed increased expression of factors important for immunomodulation and tissue repair, compared with monolayer cultured MSCs. Despite differential expression of these factors, MSC spheroids showed similar clinical efficacy in vivo as single-cell suspension MSCs. Analysis of serum samples and colon homogenates showed that local MSC therapy resulted in increased levels of interferon-γ, indoleamine 2,3-dixoygenase, and interleukin-10.
Endoscopic injections of MSCs and MSC spheroids in the inflamed colon attenuate DSS-induced colitis. Our data show that endoscopic injection can be a feasible and effective novel application route for MSC therapy in patients with luminal IBD.
间充质基质细胞（MSCs）因其具有免疫调节和再生特性，是炎症性肠病（IBD）的潜在治疗方法。然而，当全身注射时，只有一小部分细胞（如果有的话）到达发炎的结肠。在这项研究中，我们评估了将 MSCs 内镜注射到发炎的结肠肠壁中是否会影响实验性结肠炎的进程。此外，我们研究了将聚集的 MSC 注射到球体中是否可以增强其治疗能力。
比较了单层培养的 MSC 用于抗炎和促再生因子的体内 MSC 聚集物和体外 MSC 球体的表达水平。随后，在建立的葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠中，内镜注射 MSC 和 MSC 球体。
内镜注射的 MSC 和 MSC 球体均缓解了 DSS 诱导的结肠炎。此外，与单层培养的 MSC 相比，体内和体外 MSC 球体均显示出免疫调节和组织修复重要因子的表达增加。尽管这些因子的表达存在差异，但 MSC 球体在体内显示出与单细胞悬浮 MSC 相似的临床疗效。对血清样本和结肠匀浆的分析表明，局部 MSC 治疗导致干扰素-γ、吲哚胺 2,3-二氧酶和白细胞介素-10 的水平升高。
将 MSCs 和 MSC 球体内镜注射到发炎的结肠中可减轻 DSS 诱导的结肠炎。我们的数据表明，内镜注射可能是 IBD 患者 MSC 治疗的一种可行且有效的新应用途径。
