Cell-based therapies in preclinical models of necrotizing enterocolitis: a systematic review and meta-analysis.

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING
Camille Maltais-Bilodeau, Ewa Henckel, Marc-Olivier Deguise, Flore Lesage, Kelly D Cobey, Nadera Ahmadzai, Becky Skidmore, Emanuela Ferretti, Bernard Thébaud
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Abstract

Necrotizing enterocolitis (NEC) remains an incurable gut complication of prematurity with significant morbidity and mortality. Cell therapies, including mesenchymal stromal cells (MSCs), may be a promising treatment given their anti-inflammatory and regenerative potential. We assessed the effect of MSCs and other cell therapies (not classified as MSCs) on incidence, severity, and mortality in preclinical models of NEC. Bibliographic and gray literature searches yielded 17 371 records with 107 full-text articles assessed and ultimately 16 studies were included. These studies featured only rodents NEC models via combination of hyperosmolar feeds, hypoxia, hypothermia, or lipopolysaccharides. Ten studies used interventions with MSCs. Only 2 met the minimal criteria to define MSCs proposed by the International Society for Cell & Gene Therapy (ISCT). The overall risk of bias was assessed as high partly due to paucity of data with important gaps in reporting, reinforcing the importance of rigorous research framework, appropriate cell-therapy and outcome reporting in preclinical research. A reduction in the incidence of NEC (odds ratio [OR] 0.32, 95% CI [0.17, 0.62]), severe NEC (OR 0.30, 95% CI [0.18, 0.50]), and mortality (OR 0.30, 95% CI [0.16, 0.55]) was noted with MSCs treatment, seemingly more pronounced for ISCT-defined (ISCT+) MSCs. Amniotic fluid stem cells, neural stem cells, and placenta stem cells also showed a reduction in these measures. Given their accessibility (ie, umbilical cord) and proven safety profile in extremely preterm infants, our analysis provides a foundation for considering MSCs as promising candidate that requires further evaluation for the treatment of NEC.

细胞治疗坏死性小肠结肠炎的临床前模型:系统回顾和荟萃分析。
坏死性小肠结肠炎(NEC)仍然是一种无法治愈的早产儿肠道并发症,具有显著的发病率和死亡率。细胞疗法,包括间充质基质细胞(MSCs),可能是一种很有前途的治疗方法,因为它们具有抗炎和再生的潜力。我们评估了MSCs和其他细胞疗法(未归类为MSCs)对NEC临床前模型的发病率、严重程度和死亡率的影响。参考书目和灰色文献检索产生了17 371条记录,评估了107篇全文文章,最终纳入了16项研究。这些研究仅通过高渗饲料、低氧、低温或脂多糖的组合来研究啮齿动物NEC模型。10项研究使用了MSCs干预。只有2个符合国际细胞与基因治疗学会(ISCT)提出的定义间充质干细胞的最低标准。偏倚的总体风险被评估为高,部分原因是数据缺乏,报告存在重大空白,这加强了严格的研究框架、适当的细胞治疗和临床前研究结果报告的重要性。MSCs治疗降低了NEC(比值比[OR] 0.32, 95% CI[0.17, 0.62])、严重NEC(比值比[OR] 0.30, 95% CI[0.18, 0.50])和死亡率(比值比[OR] 0.30, 95% CI[0.16, 0.55])的发生率,似乎在ISCT定义的(ISCT+) MSCs中更为明显。羊水干细胞、神经干细胞和胎盘干细胞也显示出这些指标的降低。鉴于MSCs的可及性(即脐带)和在极早产儿中已证实的安全性,我们的分析为考虑MSCs作为有希望的候选物提供了基础,需要进一步评估其用于NEC的治疗。
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来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
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