Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 475 |
| Journal | Frontiers in Pediatrics |
| Volume | 7 |
| DOIs | |
| State | Published - Nov 14 2019 |
Funding
We thank Lucy Minturn and Pap Kashireddy for their dedication to this project and assistance with patient enrollment and data collection. We are indebted to the families for their participation, and to the Labor & Delivery and Neonatal Intensive Care Unit Staff at Prentice Women's Hospital for their outstanding support and teamwork. Funding. This work was supported by an investigator-initiated research grant from Viacord (co-PIs: KM and SC). This grant provided the collection kits, lab processing, and banking services, and nursing salary support for tissue collection. The work was also supported by the National Heart Lung Blood Institute (Grant #R01 HL139798, PI: KM) for research and laboratory personnel and resources to complete the biospecimen processing, archive, and laboratory assays. This work was supported by an investigator-initiated research grant from Viacord (co-PIs: KM and SC). This grant provided the collection kits, lab processing, and banking services, and nursing salary support for tissue collection. The work was also supported by the National Heart Lung Blood Institute (Grant #R01 HL139798, PI: KM) for research and laboratory personnel and resources to complete the biospecimen processing, archive, and laboratory assays.
Keywords
- bronchopulmonary dysplasia
- cord blood
- cytokines
- neonatal outcome
- premature infant
- stem cells
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health