Lesage F, Pranpanus S, Bosisio F M, Jacobs M, Ospitalieri S, Toelen J, Deprest J
Department of Development and Regeneration, KU Leuven-University of Leuven, Leuven, Belgium.
Department of Obstetrics and Gynecology, Prince of Songkla University, Songkhla, Thailand.
Hernia. 2017 Dec;21(6):973-982. doi: 10.1007/s10029-017-1635-6. Epub 2017 Jul 27.
Surgical restoration of soft tissue defects often requires implantable devices. The clinical outcome of the surgery is determined by the properties inherent to the used matrix. Mesenchymal stem cells (MSC) modulate the immune processes after in vivo transplantation and their addition to matrices is associated with constructive remodeling. Herein we evaluate the potential of MSC derived from the amniotic fluid (AF-MSC), an interesting MSC source for cell therapeutic applications in the perinatal period, for immune modulation when added to a biomaterial.
We implant cell free small intestinal submucosa (SIS) or SIS seeded with AF-MSC at a density of 1 × 10/cm subcutaneously at the abdominal wall in immune competent rats. The host immune response is evaluated at 3, 7 and 14 days postoperatively.
The matrix-specific or cellular characteristics are not altered after 24 h of in vitro co-culture of SIS with AF-MSC. The host immune response was not different between animals implanted with cell free or AF-MSC-seeded SIS in terms of cellular infiltration, vascularity, macrophage polarization or scaffold replacement. Profiling the mRNA expression level of inflammatory cytokines at the matrix interface shows a significant reduction in the expression of the pro-inflammatory marker Tnf-α and a trend towards lower iNos expression upon AF-MSC-seeding of the SIS matrix. Anti-inflammatory marker expression does not alter upon cell seeding of matrix implants.
We conclude that SIS is a suitable substrate for in vitro culture of AF-MSC and fibroblasts. AF-MSC addition to SIS does not significantly modulate the host immune response after subcutaneous implantation in rats.
软组织缺损的外科修复通常需要植入式装置。手术的临床结果取决于所用基质的固有特性。间充质干细胞(MSC)在体内移植后可调节免疫过程,将其添加到基质中与建设性重塑相关。在此,我们评估了羊水来源的间充质干细胞(AF-MSC)的潜力,AF-MSC是围产期细胞治疗应用中一种有趣的MSC来源,当添加到生物材料中时对免疫调节的作用。
我们在免疫健全的大鼠腹壁皮下植入无细胞小肠黏膜下层(SIS)或接种密度为1×10⁶/cm³的AF-MSC的SIS。在术后3、7和14天评估宿主免疫反应。
SIS与AF-MSC体外共培养24小时后,基质特异性或细胞特性未改变。在细胞浸润、血管形成、巨噬细胞极化或支架置换方面,植入无细胞或接种AF-MSC的SIS的动物之间的宿主免疫反应没有差异。对基质界面处炎性细胞因子的mRNA表达水平进行分析显示,促炎标志物Tnf-α的表达显著降低,并且在SIS基质接种AF-MSC后iNos表达有降低趋势。基质植入物接种细胞后抗炎标志物表达未改变。
我们得出结论,SIS是AF-MSC和成纤维细胞体外培养的合适底物。在大鼠皮下植入后,向SIS中添加AF-MSC不会显著调节宿主免疫反应。