Variations in Umbilical Cord Hematopoietic and Mesenchymal Stem Cells With Bronchopulmonary Dysplasia
Variations in Umbilical Cord Hematopoietic and Mesenchymal Stem Cells With Bronchopulmonary Dysplasia
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DOI：
10.3389/fped.2019.00475
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发表时间：
2019-11-14
影响因子：
2.6
通讯作者：
Mestan, Karen K.
中科院分区：
文献类型：
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作者：
Chaudhury, Sonali;Saqibuddin, Juanita;Mestan, Karen K.
目的：目的：探讨脐血来源的CD 34+造血干细胞（HPSC）、脐带组织来源的CD 90+和CD 105+间充质干细胞（MSC）在支气管肺发育不良（BPD）中的表达差异。方法：我们在一家大型分娩中心（芝加哥的普伦蒂斯妇女医院）进行了一项前瞻性纵向研究。早产儿（N = 200）根据胎龄（GA）以2：1：1的比例入组：轻度早产（31-32周）、中度早产（29-30周）和极重度早产（23-28周）。使用商业银行试剂盒在出生时采集脐带血（CB）和脐带组织（CT），并分析采集血量、组织质量、CD 34+、CD 90+、CD 105+计数和浓度。采用多重免疫分析法检测74例慢性乙型肝炎患者血浆中12种细胞因子和生长因子。根据NIH共识定义定义BPD严重程度。单变量和多变量回归模型用于确定围产期协变量，并评估干细胞浓度，细胞因子和BPD结果之间的关联。结果：在入组的200例患者中（平均GA = 30 +/- 2周），30例出现轻度BPD，24例出现中度BPD，19例出现重度BPD。HPSC和MSC的浓度（通过总细胞的%CD34+、%CD90+和%CD105+测量）随早产程度增加而增加。采集参数随GA、出生体重（BW）、性别、胎膜破裂时间延长、分娩方式、绒毛膜炎和多胎妊娠而变化。中重度BPD或死亡随着GA、BW、Apgar评分降低和记录的延迟脐带夹紧而增加。CD 34+和CD 90+随着BPD的增加而增加，并与BPD的严重程度直接相关。校正协变量后，重度BPD与%CD34+（β系数= 0.9; 95%CI = 0.4-1.5; P < 0.01）和%CD90+（β系数= 0.4; 95%CI = 0.2-0.6; P < 0.001）呈正相关。CB血浆粒细胞集落刺激因子（G-CSF）与%CD90+呈负相关，并随BPD降低。低于中位G-CSF结合升高的%CD90+预测BPD（阳性预测值= 100%）。结论：CB和CT采集在BPD婴儿中产生高浓度的HPSC和MSC，伴有低循环G-CSF。这些变化表明干细胞分化和功能预测BPD的可能机制。
Objective: To test the hypothesis that umbilical cord blood-derived CD34+ hematopoietic stem cells (HPSC), cord tissue-derived CD90+ and CD105+ mesenchymal stem cells (MSC) vary with bronchopulmonary dysplasia (BPD). Methods: We conducted a prospective longitudinal study at a large birth center (Prentice Women's Hospital in Chicago, IL). Premature infants (N = 200) were enrolled in 2:1:1 ratio based on gestational age (GA): mildly preterm (31-32 weeks), moderately preterm (29-30 weeks), and extremely preterm (23-28 weeks). Cord blood (CB) and cord tissues (CT) were collected at birth using commercial banking kits, and analyzed for collection blood volume, tissue mass, CD34+, CD90+, CD105+ counts, and concentrations. Multiplex immunoassay was used to measure 12 cytokines and growth factors in CB plasma of 74 patients. BPD severity was defined according to NIH consensus definitions. Univariate and multivariate regression models were used to identify perinatal covariates and assess associations between stem cell concentrations, cytokines, and BPD outcomes. Results: Of 200 patients enrolled (mean GA = 30 +/- 2 weeks), 30 developed mild, 24 moderate, and 19 severe BPD. Concentrations of HPSC and MSC, as measured by %CD34+, %CD90+, and %CD105+ of total cells, increased with degree of prematurity. Collection parameters varied with GA, birth weight (BW), gender, prolonged rupture of membranes, mode of delivery, chorioamnionitis, and multiple gestation. Moderate-severe BPD or death was increased with lower GA, BW, Apgar scores, and documented delayed cord clamping. %CD34+ and %CD90+ were increased with BPD and directly correlated with BPD severity. Severe BPD was positively associated with %CD34+ (beta-coefficient = 0.9; 95% CI = 0.4-1.5; P < 0.01) and %CD90+ (beta-coefficient = 0.4; 95% CI = 0.2-0.6; P < 0.001) after adjustment for covariates. CB plasma granulocyte-colony stimulating factor (G-CSF) was inversely associated with %CD90+, and decreased with BPD. Below median G-CSF combined with elevated %CD90+ predicted BPD (positive predictive value = 100%). Conclusions: CB and CT collections yielded high concentrations of HPSCs and MSCs in BPD infants, accompanied by low circulating G-CSF. These variations suggest possible mechanisms by which stem cell differentiation and function predict BPD.