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.
Highlights
Premature infants are at risk for a wide array of health and neurodevelopmental problems
The frequency of successful cord blood (CB) collection was higher among mildly preterm births
These 2 conditions resulted in a positive predictive value of 100% in which all 6 cases of low Granulocyte-colony stimulating factor (G-CSF) with high %CD90+ predicted bronchopulmonary dysplasia (BPD). In this prospective study of 200 preterm births, we found that compositions of CD34+ hematopoietic stem cells (HPSC) and CD90+ mesenchymal stem cells (MSC) were increased in premature infants who developed BPD as compared with those who did not
Summary
Premature infants are at risk for a wide array of health and neurodevelopmental problems. The characteristics of CT-derived MSCs in a large cohort of preterm births has not been previously reported, to our knowledge. The composition of bankable cells for potential future use is not well-characterized [7, 8]. Another important knowledge gap is whether maternal or perinatal factors modify availability of stem cells. This variation is important in preterm births where exposure to intrauterine inflammation and oxidative stress are heightened due to perinatal complications such as chorioamnionitis, preeclampsia, and placental insufficiency [9,10,11,12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
