Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (7): 1012-1019.doi: 10.12307/2022.137
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Zhou Ying1, Zhang Huan2, Liao Song3, Hu Fanqi3, Yi Jing1, Liu Yubin1, Jin Jide1
Received:
2021-03-30
Revised:
2021-04-01
Accepted:
2021-04-19
Online:
2022-03-08
Published:
2021-10-29
Contact:
Jin Jide, MD, Associate researcher, Institute of Radiation Medicine, Academy of Military Medical Science, Academy of military Sciences, Beijing 100850, China
About author:
Zhou Ying, Master, Institute of Radiation Medicine, Academy of Military Medical Science, Academy of military Sciences, Beijing 100850, China
Supported by:
CLC Number:
Zhou Ying, Zhang Huan, Liao Song, Hu Fanqi, Yi Jing, Liu Yubin, Jin Jide. Immunomodulatory effects of deferoxamine and interferon gamma on human dental pulp stem cells[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(7): 1012-1019.
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2.3 去铁胺和干扰素γ对人牙髓干细胞相关基因表达的影响 由图3可知,血管内皮生长因子在去铁胺处理后24 h表达开始升高,并持续到48 h;在干扰素γ处理后仅在4 h时表达高于对照组;而联合处理后24 h表达明显高于对照组,并持续到48 h。白细胞介素6的表达在4 h时各预处理组均高于对照组,并持续到48 h(但在24 h去铁胺组显著降低)。肝细胞生长因子和吲哚胺2,3-双加氧酶的表达只有干扰素γ预处理组和联合预处理组高于对照组,由4 h持续到48 h。转化生长因子β1、环氧合酶2、白细胞介素4和白细胞介素10的表达则只有去铁胺预处理组和联合预处理组在24 h和48 h高于对照组。肿瘤坏死因子α诱导蛋白6的表达在处理后4 h和48 h高于对照组(但在24 h去铁胺预处理组显著降低),而联合预处理组在3个时间段均高于对照组。人类白细胞抗原G的表达在24 h只有联合预处理组高于对照组,48 h 3个预处理组均高于对照组。 相比其他组,去铁胺预处理组对血管内皮生长因子、白细胞介素6、转化生长因子β1、环氧合酶2、人类白细胞抗原G、白细胞介素4和白细胞介素10等基因的表达上调作用较显著;干扰素γ预处理组对白细胞介素6、肝细胞生长因子、吲哚胺2,3-双加氧酶和肿瘤坏死因子α诱导蛋白6等基因的表达上调较显著,而二者联合预处理后血管内皮生长因子、白细胞介素6、转化生长因子β1、环氧合酶2、白细胞介素10、肿瘤坏死因子α诱导蛋白6、人类白细胞抗原G等基因的表达均出现显著上调,但肝细胞生长因子与吲哚胺2,3-双加氧酶基因的表达在干扰素γ预处理组上调更显著。"
2.5 去铁胺联合干扰素γ对人牙髓干细胞抑制淋巴细胞增殖的影响 不同预处理的人牙髓干细胞与CFSE预染的小鼠脾淋巴细胞共培养3 d后,通过流式细胞术检测脾淋巴细胞的增殖。如图5所示,与抗CD3抗体活化的脾细胞共培养后,去铁胺或干扰素γ预处理人牙髓干细胞均抑制了脾淋巴细胞的增殖,且去铁胺联合干扰素γ预处理人牙髓干细胞抑制脾淋巴细胞的增殖作用最强。 2.6 小鼠异体移植皮片的存活时间 空白对照组小鼠移植皮片在术后7 d即开始有动物出现脱落,至观察期14 d结束所有小鼠的移植皮肤均发生脱落,平均存活时间仅为(9.25±3.20) d;单纯干细胞治疗组移植皮片的存活时间较空白对照组有所延长,平均存活时间为(11.75±2.21) d;去铁胺联合干扰素γ预处理干细胞治疗组至观察期14 d结束,仅有1只小鼠的移植皮肤在第14天发生脱落。结果表明,人牙髓干细胞可以延长小鼠异体移植皮肤的存活时间,但去铁胺联合干扰素γ预处理人牙髓干细胞的作用更为明显。"
2.8 移植皮片苏木精-伊红染色结果 如图7所示,移植后第3天,空白对照组小鼠移植皮片出现大量炎细胞浸润,出现急性脓肿,炎症反应显著,表皮和真皮均出现坏死,评分为4级;单纯干细胞治疗组移植皮片可见局灶性炎细胞浸润,有轻微表皮变性,评分为2级;去铁胺联合干扰素γ预处理干细胞治疗组移植皮片的皮肤附属器尚存完好,仅有少量炎细胞浸润,评分为1级。移植后第7天,空白对照组皮片仍显示大量炎细胞浸润,组织水肿,表皮、真皮坏死,出现慢性肉芽肿,评分为3级;单纯干细胞治疗组移植皮片可见局灶性炎性细胞浸润,有轻微表皮变性,评分为2级:去铁胺联合干扰素γ预处理干细胞治疗组移植皮片没有发现表皮变性,但可见局灶炎症细胞浸润,皮肤附属器尚存完好,评分为1级。移植后第14天,空白对照组和单纯干细胞治疗组小鼠移植皮片已完全脱落;去铁胺联合干扰素γ预处理干细胞治疗组移植皮片仅有少许炎细胞浸润,表皮、真皮结构完整,附属器尚存完好,瘢痕修复好,评分为1级。尽管在皮肤移植后,3组动物所有的移植皮片均出现被排斥现象,但人牙髓干细胞治疗减轻了对移植皮片的排斥作用,而这种作用在联合处理组更加明显,这提示去铁胺联合干扰素γ预处理促进了人牙髓干细胞诱导免疫耐受。"
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