宫内干细胞治疗多种胎儿遗传性疾病的可能性

doi:10.12307/2021.147

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (31): 5034-5039.doi: 10.12307/2021.147

• 干细胞综述 stem cell review • 上一篇下一篇

宫内干细胞治疗多种胎儿遗传性疾病的可能性

揭秋玲1，2，3，4，孙菲1，2，3，4

1南方医科大学南方医院妇产科，广东省广州市 510515；2海南医学院第一附属医院海南省人类生殖与遗传重点实验室，生殖医学科，海南省地方病(地中海贫血)临床医学研究中心，海南省海口市 570102；3海南医学院热带转化医学教育部重点实验室，海南省海口市 570102；4海南医学院第一附属医院海口市人类遗传资源保藏重点实验室，海南省海口市 570102

收稿日期:2020-06-18 修回日期:2020-06-24 接受日期:2020-08-13 出版日期:2021-11-08 发布日期:2021-04-25
通讯作者: 孙菲，博士，博士后，南方医科大学南方医院妇产科，广东省广州市 510515；海南医学院第一附属医院海南省人类生殖与遗传重点实验室，生殖医学科，海南省地方病(地中海贫血)临床医学研究中心，海南省海口市 570102；海南医学院热带转化医学教育部重点实验室，海南省海口市 570102；海南医学院第一附属医院海口市人类遗传资源保藏重点实验室，海南省海口市 570102
作者简介:揭秋玲，女，1991年生，广西壮族自治区博白县人，汉族，2016年中国医科大学毕业，主要从事妊娠相关疾病研究。
基金资助:
广东省基础与应用基础研究基金面上项目(2019A1515010019)，项目负责人：孙菲；南方医科大学南方医院院长基金(2018Z014，2017C001)，项目负责人：孙菲；国家自然科学基金(81660433)，项目参与人：孙菲

Possibility of in utero stem cell therapy for multiple fetal genetic diseases

Jie Qiuling1, 2, 3, 4, Sun Fei1, 2, 3, 4

Received:2020-06-18 Revised:2020-06-24 Accepted:2020-08-13 Online:2021-11-08 Published:2021-04-25
Contact: Sun Fei, MD, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China; Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Department of Reproductive Medicine, Hainan Provincial Clinical Research Center for Thalassemia, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China; Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 570102, Hainan Province, China; Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
About author:Jie Qiuling, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China; Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Department of Reproductive Medicine, Hainan Provincial Clinical Research Center for Thalassemia, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China; Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University, Haikou 570102, Hainan Province, China; Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China
Supported by:
the General Project of Basic and Applied Basic Research Fund of Guangdong Province, No. 2019A1515010019 (to SF); Presidential Foundation of Nanfang Hospital, Southern Medical University, No. 2018Z014 (to SF), No. 2017C001 (to SF); the National Natural Science Foundation of China, No. 81660433 (to SF)

摘要/Abstract

摘要：

文题释义：

宫内干细胞治疗：利用自体或同种异体干细胞进行宫内疾病的治疗。目前宫内干细胞治疗只在严重联合免疫缺陷症中取得成功，其他疾病仍处于研究探索阶段。宫内干细胞治疗将胎儿医学推向细胞及分子水平，应用前景广阔。
造血干细胞：是指具有自我更新和分化为多系血细胞的一类祖细胞，具有在胎儿时期和成人时期维持造血功能的能力。造血干细胞最早应用于宫内干细胞移植治疗，也是目前关于宫内干细胞移植治疗研究最为广泛的细胞。
背景：产前诊断筛查技术的发展使得产前治疗成为可能。对于多种胎儿遗传性疾病，宫内干细胞治疗具有显著的优势。
目的：通过目前已有的实验研究和临床资料分析宫内干细胞治疗产前胎儿疾病的可行性。
方法：应用计算机检索中国知网、万方医学网、PubMed 数据库中的相关文献，检索时间从建库至2020-06-16，检索中文关键词为“宫内干细胞治疗，胎儿”，英文关键词为“in utero stem cell therapy，fetal”。
结果与结论：随着产前诊断筛查技术和干细胞治疗技术的发展，宫内干细胞在多种胎儿遗传性疾病治疗中具有显著的优势。胎儿自身发育的生理特点也为宫内干细胞移植提供了条件。临床前动物实验研究从嵌合体植入水平和免疫耐受等方面为宫内干细胞移植治疗的临床应用奠定了基础。近年来，产前诊断筛查技术的发展，伴随高通量分子检测、微创手术等方法，可在妊娠早期检测出多种胎儿疾病，也使得产前宫内治疗成为可能。
https://orcid.org/0000-0002-1338-0888 (揭秋玲)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 宫内干细胞, 免疫, 遗传性疾病, 严重联合免疫缺陷症, 造血干细胞, 间充质干细胞, 羊水干细胞, 治疗, 综述

Abstract: BACKGROUND: The development of prenatal diagnosis and screening technology has made prenatal treatment possible. For a variety of fetal genetic diseases, in utero stem cell therapy has significant advantages.
OBJECTIVE: To analyze the feasibility of in utero stem cell therapy in prenatal fetal diseases through the existing experimental research and clinical data.
METHODS: Databases of PubMed, Wanfang and CNKI were searched for the articles published from the inception to June 16, 2020. The keywords were “in utero stem cells, fetal” in English and Chinese, respectively.
RESULTS AND CONCLUSION: With the development of prenatal diagnosis screening technology and stem cell therapy technology, in utero stem cell therapy has a significant advantage in the treatment of various fetal genetic diseases. The physiological characteristics of fetal development also provide conditions for in utero stem cell transplantation. The preclinical animal experiment research has laid the foundation for the clinical application of in utero stem cell transplantation treatment from the aspects of chimera implantation level and immune tolerance. In recent years, the development of prenatal diagnosis and screening technology, along with high-throughput molecular testing and minimally invasive surgery, can detect a variety of fetal diseases in early pregnancy, and also makes prenatal intrauterine treatment possible.

Key words: in utero stem cell therapy, immunity, hereditary diseases, severe combined immunodeficiency, hematopoietic stem cell therapy, mesenchymal stem cell therapy, amniotic fluid stem cell, therapy, review

中图分类号:

揭秋玲, 孙菲. 宫内干细胞治疗多种胎儿遗传性疾病的可能性[J]. 中国组织工程研究, 2021, 25(31): 5034-5039.

Jie Qiuling, Sun Fei. Possibility of in utero stem cell therapy for multiple fetal genetic diseases[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(31): 5034-5039.

参考文献

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引言

目前，针对胎儿疾病开展的治疗方法多为外科手术。早在1982年，HARRISON等[1]报道了第1例宫内外科手术成功治疗先天性肾盂积水。此后，在胎儿开放性手术和胎儿镜方面有长足的进展，如开放性手术修复脊髓脊膜突出、脑积水、先天性肺损伤，以及利用胎儿镜进行双胎输血综合征、膈疝造成的气管闭塞等治疗[2-4]。目前胎儿手术多为纠正胎儿解剖学异常，而对于多种基因遗传病，宫内干细胞治疗具有显著的优势。
基因疾病对胚胎和胎儿发育具有不可逆转的重要损伤和影响。多种遗传代谢性疾病与神经系统发育损伤密切相关，如Lesch-Nyhan综合征、Tay Sachs病和Gaucher’s病急性神经病变等，由于无法逆转发育过程中疾病的损伤，这些患儿产后利用目前最先进的治疗手段也仅仅能够达到非常有限的治疗效果[5-6]。宫内干细胞有可能在早期治疗这些影响胚胎和胎儿发育的疾病，避免进一步的产后损伤。许多疾病如先天遗传性基因疾病、血红蛋白病、免疫缺陷和代谢疾病等发病率较低，但是这些疾病却带来较重的社会负担。对于那些即使能够产后治愈的疾病，如能够产前治愈，也具有明显的优势和减轻社会负担。
分娩一个健康的婴儿，不仅对胎儿发育具有多种生理上的益处，对整个社会来说也有显著的优势。胎儿发育的独特条件，使得在其发育过程中进行干细胞移植，将比产后治疗更为经济有效，而胎儿外科手术、产前早期超声诊断、产前早期分子诊断，都为宫内干细胞移植提供了有利的条件。
随着再生医学的发展，多种干细胞研究取得了瞩目的成果。虽然理论上多种干细胞都具有自我更新和分化的潜能，但是考虑到安全性和伦理等问题，目前关于宫内干细胞治疗的研究还是以宫内造血干细胞移植治疗(in utero
hematopoietic stem cell transplantation，IUHSCT)为主。该文章对宫内干细胞治疗胎儿疾病进行了综述，以造血干细胞移植治疗为主，就目前宫内干细胞治疗的原理、动物实验、临床试验、障碍和风险的发展历程和进展进行论述，并对将来临床应用和广阔的治疗前景进行展望。
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

宫内干细胞治疗多种胎儿遗传性疾病的可能性

Possibility of in utero stem cell therapy for multiple fetal genetic diseases

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