Karaoz Erdal, Tepekoy Filiz, Yilmaz Irem, Subasi Cansu, Kabatas Serdar
Department of Histology & Embryology, Faculty of Medicine, İstinye University, İstanbul, Turkey.
Center for Stem Cell and Tissue Engineering Research & Practice, İstinye University, İstanbul, Turkey.
J Korean Neurosurg Soc. 2019 Mar;62(2):153-165. doi: 10.3340/jkns.2018.0035. Epub 2019 Feb 27.
Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestinpositive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI.
rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100β, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-β, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors.
rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), β3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined.
Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.
脊髓损伤（SCI）是一个非常严重的健康问题，通常由外伤引起，并伴有炎症指标升高。基于干细胞的治疗为其功能恢复提供了一些有价值的策略。从胰岛（PI）中分离出的巢蛋白阳性祖细胞和/或干细胞（SC）具有间充质干细胞（MSC）的特征。因此，我们旨在分析大鼠胰岛来源干细胞（rPI-SC）移植对SCI后功能恢复的影响以及炎症因子水平。
分离培养rPI-SC，并通过流式细胞术和免疫荧光分析确定其MSC特征。将实验大鼠分为三组：1）椎板切除术和创伤组，2）椎板切除术、创伤和磷酸盐缓冲盐水（PBS）组，3）椎板切除术+创伤+干细胞组。将绿色荧光蛋白（GFP）标记的rPI-SC移植到受伤大鼠的脊髓中。用Basso、Beattie和Bresnahan（BBB）评分评估其运动能力。4周后，分析脊髓切片中GFP标记的干细胞，并对波形蛋白、S100β、脑源性神经营养因子（BDNF）、2',3'-环核苷酸3'-磷酸二酯酶（CNPase）、血管内皮生长因子（VEGF）以及促炎因子（白细胞介素[IL]-6、转化生长因子[TGF]-β、巨噬细胞炎性蛋白[MIP]-2、髓过氧化物酶[MPO]）和抗炎因子（IL-1受体拮抗剂）进行染色。
rPI-SC显示出MSC特征，并表达神经和胶质细胞标志物，包括BDNF、胶质纤维酸性蛋白（GFAP）、纤连蛋白、微管相关蛋白-2a、b（MAP2a、b）、β3-微管蛋白和巢蛋白以及抗炎前列腺素E2受体EP3。BBB评分显示第3组有显著的运动恢复。GFP标记的细胞定位于损伤部位。此外，还检测到促炎因子水平降低，抗炎因子强度增加。
PI-SC移植可能是改善脊髓创伤后功能恢复的有效策略。
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