Department of Clinical Sciences Lund, Paediatrics, Lund University, Skåne University Hospital, Lund, Sweden.
Pediatrics, Division of Neonatology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Cochrane Database Syst Rev. 2023 Feb 15;2(2):CD013201. doi: 10.1002/14651858.CD013201.pub3.
Germinal matrix-intraventricular haemorrhage (GMH-IVH) and encephalopathy of prematurity (EoP) remain substantial issues in neonatal intensive care units worldwide. Current therapies to prevent or treat these conditions are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal studies. This is an update of the 2019 review, which did not include EoP.
To evaluate the benefits and harms of stem cell-based interventions for prevention or treatment of GM-IVH and EoP in preterm infants.
We used standard, extensive Cochrane search methods. The latest search was April 2022.
We attempted to include randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing 1. stem cell-based interventions versus control; 2. mesenchymal stromal cells (MSCs) of type or source versus MSCs of other type or source; 3. stem cell-based interventions other than MSCs of type or source versus stem cell-based interventions other than MSCs of other type or source; or 4. MSCs versus stem cell-based interventions other than MSCs. For prevention studies, we included extremely preterm infants (less than 28 weeks' gestation), 24 hours of age or less, without ultrasound diagnosis of GM-IVH or EoP; for treatment studies, we included preterm infants (less than 37 weeks' gestation), of any postnatal age, with ultrasound diagnosis of GM-IVH or with EoP.
We used standard Cochrane methods. Our primary outcomes were 1. all-cause neonatal mortality, 2. major neurodevelopmental disability, 3. GM-IVH, 4. EoP, and 5. extension of pre-existing non-severe GM-IVH or EoP. We planned to use GRADE to assess certainty of evidence for each outcome.
We identified no studies that met our inclusion criteria. Three studies are currently registered and ongoing. Phase 1 trials are described in the 'Excluded studies' section.
AUTHORS' CONCLUSIONS: No evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment or prevention of GM-IVH or EoP in preterm infants. We identified three ongoing studies, with a sample size range from 20 to 200. In two studies, autologous cord blood mononuclear cells will be administered to extremely preterm infants via the intravenous route; in one, intracerebroventricular injection of MSCs will be administered to preterm infants up to 34 weeks' gestational age.
脑室内出血（GMH-IVH）和早产儿脑病（EoP）仍然是全球新生儿重症监护病房的重要问题。目前预防或治疗这些疾病的治疗方法有限。基于干细胞的治疗方法为修复、恢复或再生受损脑组织提供了一种潜在的治疗方法。这些临床前发现现在已经促成了正在进行的新生儿人体研究。这是对 2019 年审查的更新，其中不包括 EoP。
评估基于干细胞的干预措施预防或治疗早产儿 GM-IVH 和 EoP 的益处和危害。
我们使用了标准的、广泛的 Cochrane 搜索方法。最新的搜索是在 2022 年 4 月进行的。
我们试图纳入随机对照试验、准随机对照试验和群组试验，比较 1. 基于干细胞的干预措施与对照；2. 同种类型或来源的间充质基质细胞（MSCs）与其他类型或来源的 MSCs；3. 除 MSCs 以外的基于干细胞的干预措施与除 MSCs 以外的其他类型或来源的基于干细胞的干预措施；或 4. MSCs 与除 MSCs 以外的基于干细胞的干预措施。对于预防研究，我们纳入了极早产儿（胎龄不足 28 周），24 小时或以下，没有 GM-IVH 或 EoP 的超声诊断；对于治疗研究，我们纳入了胎龄不足 37 周的早产儿，任何出生后年龄，有 GM-IVH 的超声诊断或有 EoP。
我们使用了标准的 Cochrane 方法。我们的主要结局是 1. 全因新生儿死亡率，2. 主要神经发育障碍，3. GM-IVH，4. EoP，和 5. 先前存在的非严重 GM-IVH 或 EoP 的扩展。我们计划使用 GRADE 来评估每个结局的证据确定性。
我们没有发现符合纳入标准的研究。目前有三项研究正在注册和进行中。阶段 1 试验在“排除研究”部分进行了描述。
目前尚无证据可评估基于干细胞的干预措施在治疗或预防早产儿 GM-IVH 或 EoP 方面的益处和危害。我们确定了三项正在进行的研究，样本量范围为 20 至 200。在两项研究中，将通过静脉途径向极早产儿输注自体脐带血单核细胞；在一项研究中，将向胎龄达 34 周的早产儿脑室内注射 MSCs。
