脐血来源干细胞治疗早产儿疾病临床研究进展与挑战

doi:10.12372/jcp.2023.23e0634

临床儿科杂志 ›› 2023, Vol. 41 ›› Issue (10): 646-653.doi: 10.12372/jcp.2023.23e0634

脐血来源干细胞治疗早产儿疾病临床研究进展与挑战

李芳, 王利

重庆医科大学附属妇女儿童医院儿科（重庆 401120）

收稿日期:2023-07-11 出版日期:2023-10-15 发布日期:2023-10-08
作者简介:李芳，儿科学博士，主任医师，重庆医科大学硕士研究生导师，重庆市中青年医学高端人才。现任重庆市妇幼保健院（重庆医科大学附属妇女儿童医院）副院长。兼任中国医师协会新生儿科医师分会生命支持专委会副主任委员、中华医学会围产医学专委会产房安全与助产学组委员、重庆医学会围产医学分会副主任委员等学术任职。先后在丹麦哥本哈根大学和美国奥古斯塔大学儿童医学中心担任访问学者。主持国家自然科学基金、省部级重点课题等6项，十四五科技部重大专项骨干成员，以第一作者或通信作者在Lancet Network Open、Advanced Science等权威杂志上发表SCI论文10余篇，执笔制定指南/专家共识5篇，获得重庆市科技进步二等奖1项，中国妇幼健康科学技术三等奖1项，参编专著3部。担任BMC Pediatrics、《临床儿科杂志》青年编委，《中南大学学报（医学版）》《检验医学与临床》等杂志审稿专家。ORCID：0000-0001-9038-4877
基金资助:
国家重点研发计划(2022YFC2704801);重庆市自然科学基金(cstc2021jcyj-msxmX0257);重庆市科卫联合重点项目(2023ZDXM024);重庆市科卫联合青年项目(2023QNXM037)

Progress and challenges in clinical research of umbilical cord blood transplantation for the treatment of premature infant diseases

LI Fang, WANG Li

Department of Pediatrics, Women and Children’s Hospital of Chongqing Medical University, Chongqing 401120, China

Received:2023-07-11 Online:2023-10-15 Published:2023-10-08

摘要/Abstract

摘要：

尽管新生儿疾病治疗技术取得了巨大进步，早产儿疾病如支气管肺发育不良、围生期脑损伤和坏死性小肠结肠炎等疾病仍是我国新生儿死亡的重要原因，也严重影响存活早产儿远期生存质量。探寻更有效的防治手段，是新生儿领域关注的焦点。过去20年来，干细胞治疗特别是脐血来源的干细胞作为多种早产疾病的新型治疗策略，取得了鼓舞人心的临床前研究和临床研究结果，现就脐血来源干细胞治疗在早产儿疾病治疗中的临床研究与应用进展作一介绍，分别就脐血来源干细胞治疗的研究现状、存在问题及挑战进行探讨。

关键词: 细胞治疗, 脐血来源干细胞, 早产儿, 临床研究

Abstract:

Despite great progress in the treatment of neonatal diseases, complications of preterm infants such as bronchopulmonary dysplasia, perinatal brain injury and necrotizing enterocolitis are still leading causes of neonatal mortality and long term morbidity. Exploring more effective therapies for the prevention or treatment for the complications of preterm infants are the concerns in neonatology. Stem cell therapy especially umbilical cord blood transplantation, have been explored as a new therapeutic option in premature infant diseases, with very promising preclinical and clinical results over the past 20 years. This article outlined the clinical progress, prospects and challenges of stem cells derived from umbilical cord blood in preterm diseases.

Key words: cell therapy, umbilical cord blood-derived stem cell, preterm infant, clinical research

李芳, 王利. 脐血来源干细胞治疗早产儿疾病临床研究进展与挑战[J]. 临床儿科杂志, 2023, 41(10): 646-653.

LI Fang, WANG Li. Progress and challenges in clinical research of umbilical cord blood transplantation for the treatment of premature infant diseases[J]. Journal of Clinical Pediatrics, 2023, 41(10): 646-653.

图/表 1

表1

UCBT在新生儿疾病的临床研究"

疾病	研究阶段	移植途径及时机	干细胞类型/来源	结论	参考文献
BPD	I期	气管内、生后7~14 d	同种异体hUCB-MSCs、单次、低剂量（1×10⁷/kg）或高剂量（2×10⁷/kg）	近期（移植后84 d）、远期（校正GA 2岁）安全	Chang等^[29]
	I期	气管内、生后5~14 d	同种异体hUCB-MSCs、单次、低剂量（1×10⁷/kg）或高剂量（2×10⁷/kg）	移植后84 d内无移植相关不良事件	Powell等^[30]
	I期	静脉、诊断BPD后	同种异体hUCB-MSCs、单次、6例低剂量组（1×10⁶/kg）、7例高剂量组（5×10⁶/kg）	移植后28 d内无移植相关不良事件	Xia等^[31]
	I期	静脉、诊断BPD后	同种异体hUCB-MSCs、2剂（每剂1×10⁶/kg）	移植后1年无移植相关不良事件	Nguyen等^[32]
	II期	气管内、生后（11.8± 2.0）d	同种异体hUCB-MSCs、单次1×10⁷/kg	干细胞组炎症因子水平较低、死亡/中重度BPD无显著差异；亚组分析23~24周组重度BPD较低	Ahn等^[33]
	II期	静脉、生后8 h内	自体脐带血单个核细胞、单次5×10⁷ /kg	干细胞组机械通气和需氧治疗时间显著减少	Ren等^[34]
	II期	静脉、生后24 h内	自体脐带血单个核细胞、单次5×10⁷ /kg	干细胞组存活者的中重度BPD发病率显著降低、呼吸机拔管率更高、校正18~24月龄发育迟缓更低	Zhu xiao等^[35]
IVH	I期	脑室内、诊断重度IVH后7 d内	同种异体hUCB-MSCs、单次、低剂量（5×10⁶/kg）或高剂量（2×10⁷/kg）	近期结果：安全可行；计划随访至2岁	Ahn等^[38]
HIE	I期	静脉、生后最初72（48）h内最多输注4次	（1~5）×10⁷ /kg自体脐带血	住院结局相似、干细胞移植组1岁Bayley III评分更好	Cotton等^[39]
HIE	I期	静脉、生后12~72 h内共接受3次	自体脐带血	随访至18月龄安全可行	Tsuji等^[40]
NEC	个案报道	静脉、NEC术后	同种异体hUCB-MSCs 1×10⁷/kg	1岁的体格和神经发育和同龄儿童相当	Akduman等^[42]
早产儿贫血	I期	静脉	5例、自体脐带血移植	安全可行	Rudnicki等^[28]
早产儿贫血	I期	静脉	5例、自体脐带血移植	安全可行	Kotowski等^[43]
左心发育不良综合征	I期	心肌内注射、接受II期手术时	自体脐带血单个核细胞（1~3）×10⁶	随访6个月：安全可行	Burkhar等^[44]

表1

参考文献 58

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脐血来源干细胞治疗早产儿疾病临床研究进展与挑战

Progress and challenges in clinical research of umbilical cord blood transplantation for the treatment of premature infant diseases

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