Yu Na-Hee, Chun So Young, Ha Yun-Sok, Kim Hyun Tae, Lih Eugene, Kim Dae Hwan, Kim Jeongshik, Chung Jae-Wook, Song Phil Hyun, Yoo Eun Sang, Chung Sung Kwang, Han Dong Keun, Kim Bum Soo, Kwon Tae Gyun
1BioMedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Republic of Korea.
2Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Republic of Korea.
Tissue Eng Regen Med. 2018 Oct 11;16(1):81-92. doi: 10.1007/s13770-018-0162-6. eCollection 2019 Feb.
Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated .
For renal regeneration, transported AFSCs were seeded on a poly(lactide--glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery.
The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of pro-inflammatory cytokines and fibrotic factors; enhanced expression of the genes , , , and ; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells.
This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, safety, and tissue regeneration potency.
尽管干细胞治疗取得了重大进展,但我们对长期运输细胞的特性和组织再生能力的了解仍不足。在之前的一项研究中,我们确定了羊水干细胞(AFSCs)的最佳细胞运输条件。在本研究中,对长期运输细胞的靶组织再生进行了验证。
为了实现肾脏再生,将运输后的AFSCs接种在聚(丙交酯-乙交酯)支架上,并植入部分切除的肾脏中。从形态重建、组织学微观结构重塑、免疫细胞浸润、诱导细胞的存在、向远处器官的迁移、炎症/纤维化/肾分化相关因子的表达以及功能恢复等方面,将运输细胞的靶组织再生与新鲜收获的细胞进行比较。
植入运输细胞的肾脏在40周的观察期内显示出总肾体积的恢复、肾小球/肾小管的再生、低CD4/CD8浸润,且未发生癌症。AFSCs逐渐消失,未迁移至肝脏、肺或脾脏。我们观察到促炎细胞因子和纤维化因子的低表达水平;基因、、和的表达增强;以及血尿素氮和肌酐值显著降低。新鲜收获的细胞与运输细胞的表现之间没有统计学差异。
本研究表明,在优化条件下长期运输的细胞可用于细胞治疗,而不会对干细胞特性、安全性和组织再生能力产生不利影响。