Abo-Aziza Faten A M, Zaki Abdel Kader A, Abo El-Maaty Amal M
Department of Parasitology and Animal Diseases, Veterinary Research Division, National Research Centre, Cairo, Egypt.
Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia.
Cell Regen. 2019 Nov 21;8(2):58-71. doi: 10.1016/j.cr.2019.11.001. eCollection 2019 Dec.
This study aimed to clarify the potentiality of bone marrow mesenchymal stem cells (BM-MSC) transplantation with albendazole (ABZ) on the modulation of immune responses against hydatid cyst antigens and the regeneration of injured livers in experimentally infected rats. Three different antigens of hydatid cyst fluid (HCF), hydatid cyst protoscolex (HCP) and hydatid cyst germinal layer (HCG) were isolated and their antigenic potencies were determined. The ultrasound, immunological and pathological criteria were investigated. Counting of 80% confluence BM-MSC was 4.68 × 10 cells/cm with 92.24% viability. Final population doublings score was 65.31 that indicated proliferation and self-renewability. Phenotyping of BM-MSC showed expression of CD73 and CD29 without exhibition of CD34 and CD14. Ultrasound examination showed multiple hydatid cysts in liver with low blood flow and spleenomegaly 8 weeks' post infection. No significant differences were noted in cystic diameter in uni-cyst liver at 2nd and 4th weeks following ABZ treatment while it was significantly decreased (P < 0.05) following transplantation of BM-MSC + ABZ treatment comparing to experimentally infected untreated group. Igs and IgG responses to the three antigens were significantly elevated while elevation in IgM response was only to HCG (P < 0.05). ABZ treatment accompanied with significant decrease in Igs and IgG titers against HCF and HCG only at 4th week post treatment (P < 0.05). However, Igs titer against HCF, HCP and HCG was significantly decreased at the 4th week following transplantation of BM-MSC + ABZ. Interestingly, the combination of BM-MSC + ABZ treatment resulted in reduction of Igs response to HCP to normal level as that of healthy control. Experimental infection resulted in elevation of TNF-α and IL-6 (P < 0.05) while, IL-4 and IL-10 decreased (P < 0.01). After transplantation of BM-MSC + ABZ treatment, serum TNF-α and IL-6 concentrations were reduced (P < 0.05) at both the 2nd and 4th weeks. However, IL-4 and IL-10 concentrations were significantly elevated (P < 0.05) only at 4th week following transplantation of BM-MSC + ABZ treatment. In conclusion, BM-MSC transplantation following ABZ administration can regenerate injured liver tissue without complete disappearance of hydatid cyst. In addition, it can modulate host protective humeral and cell mediated immune responses against hydatid cyst antigens. Therefore, the current study encourages to move to the step of performing clinical trials in humans.
本研究旨在阐明阿苯达唑（ABZ）联合骨髓间充质干细胞（BM-MSC）移植对实验性感染大鼠针对包虫囊肿抗原的免疫反应调节及损伤肝脏再生的潜力。分离出包虫囊肿液（HCF）、包虫囊肿原头节（HCP）和包虫囊肿生发层（HCG）的三种不同抗原，并测定其抗原效力。研究了超声、免疫学和病理学标准。80%汇合的BM-MSC计数为4.68×10个细胞/cm，活力为92.24%。最终群体倍增分数为65.31，表明其具有增殖和自我更新能力。BM-MSC的表型分析显示CD73和CD29表达阳性，而CD34和CD14未表达。超声检查显示感染8周后肝脏有多个包虫囊肿，血流低，脾脏肿大。ABZ治疗后第2周和第4周，单囊肿肝脏的囊肿直径无显著差异，而与未治疗的实验感染组相比，BM-MSC + ABZ治疗后囊肿直径显著减小（P < 0.05）。对三种抗原的Ig和IgG反应显著升高，而IgM反应仅对HCG升高（P < 0.05）。ABZ治疗仅在治疗后第4周使针对HCF和HCG的Ig和IgG滴度显著降低（P < 0.05）。然而，BM-MSC + ABZ移植后第4周，针对HCF、HCP和HCG的Ig滴度显著降低。有趣的是，BM-MSC + ABZ治疗组合使针对HCP的Ig反应降低至健康对照的正常水平。实验性感染导致TNF-α和IL-6升高（P < 0.05），而IL-4和IL-10降低（P < 0.01）。BM-MSC + ABZ治疗移植后第2周和第4周，血清TNF-α和IL-6浓度降低（P < 0.05）。然而，仅在BM-MSC + ABZ治疗移植后第4周，IL-4和IL-10浓度显著升高（P < .05）。总之，ABZ给药后进行BM-MSC移植可使损伤的肝组织再生，而包虫囊肿不会完全消失。此外，它可以调节宿主针对包虫囊肿抗原的保护性体液免疫和细胞介导的免疫反应。因此，本研究鼓励进入在人类中进行临床试验的阶段。
