Dataset Information

Endothelial colony-forming cells from preterm infants are increased and more susceptible to hyperoxia.

ABSTRACT:

Rationale

Preterm birth and hyperoxic exposure increase the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by impaired vascular and alveolar growth. Endothelial progenitor cells, such as self-renewing highly proliferative endothelial colony-forming cells (ECFCs), may participate in vascular repair. The effect of hyperoxia on ECFC growth is unknown.

Objectives

We hypothesize that umbilical cord blood (CB) from premature infants contains more ECFCs with greater growth potential than term CB. However, preterm ECFCs may be more susceptible to hyperoxia.

Methods

ECFC colonies were quantified by established methods and characterized by immunohistochemistry and flow cytometry. Growth kinetics were assessed in room air and hyperoxia (FI(O(2)) = 0.4).

Measurements and main results

Preterm CB (28-35 wk gestation) yielded significantly more ECFC colonies than term CB. Importantly, we found that CD45(-)/CD34(+)/CD133(+)/VEGFR-2(+) cell number did not correlate with ECFC colony count. Preterm ECFCs demonstrated increased growth compared with term ECFCs. Hyperoxia impaired growth of preterm but not term ECFCs. Treatment with superoxide dismutase and catalase enhanced preterm ECFC growth during hyperoxia.

Conclusions

Preterm ECFCs appear in increased numbers and proliferate more rapidly but have an increased susceptibility to hyperoxia compared with term ECFCs. Antioxidants protect preterm ECFCs from hyperoxia.

SUBMITTER: Baker CD

PROVIDER: S-EPMC2742761 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Publications

Endothelial colony-forming cells from preterm infants are increased and more susceptible to hyperoxia.

Baker Christopher D CD Ryan Sharon L SL Ingram David A DA Seedorf Gregory J GJ Abman Steven H SH Balasubramaniam Vivek V

American journal of respiratory and critical care medicine 20090529 5

<h4>Rationale</h4>Preterm birth and hyperoxic exposure increase the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by impaired vascular and alveolar growth. Endothelial progenitor cells, such as self-renewing highly proliferative endothelial colony-forming cells (ECFCs), may participate in vascular repair. The effect of hyperoxia on ECFC growth is unknown.<h4>Objectives</h4>We hypothesize that umbilical cord blood (CB) from premature infants contains more ECFCs w ...[more]

PMID: 19483112

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Project description:Angiogenesis is a complicated process in which perivascular cells play important roles. Multipotent mesenchymal stem/stromal cells (MSCs) from distinct tissues have been proved to be proangiogenic and share functional properties and gene expression profiles with perivascular cells. However, different tissues derived MSCs may exhibit different potential for clinical applications. Accordingly, comparative studies on different MSCs are essential. Here, we characterized MSCs from adipose (ADSCs), umbilical cord (UCMSCs), and endometrium (EMSCs) in terms of the surface antigen expression, differentiation ability, and the ability of angiogenesis promotion on endothelial colony-forming cells (ECFCs) both in vitro and in vivo. No significant differences in immunophenotype and differentiation were observed. In addition, three types of MSCs all located around tubular-like structures formed by ECFCs in coculture system on matrigel. But ECFCs seeded on ADSCs monolayer formed more organized capillary-like network than that on UCMSCs or EMSCs. When suspended with ECFCs in matrigel and implanted into nude mice, ADSCs promoted more functional vessel formation after 7 days. Moreover, in murine hindlimb ischemia model, cotransplantation of ECFCs with ADSCs was significantly superior to UCMSCs and EMSCs in promoting perfusion recovery and limb salvage. Furthermore, ADSC-conditioned medium (CM) contained more proangiogenic factors (such as vascular endothelial growth factor-A, platelet-derived growth factor BB, and basic fibroblast growth factor) and less inhibitory factor (such as thrombospondin-1), when compared with UCMSC-CM and EMSC-CM. And ADSC-CM more durably stabilized the vascular-like structures formed by ECFCs on matrigel and promoted ECFCs migration more efficiently. In summary, MSCs from adipose show significantly efficient promotion on angiogenesis both in vitro and in vivo than UCMSCs and EMSCs. Hence, ADSCs may be recommended as a more suitable source for treating hindlimb ischemia.

Project description:Artificial small-diameter vascular grafts remain an unmet need in modern medicine, due to the thrombosis and neointimal hyperplasia that plague currently available synthetic devices. Tissue engineering techniques, including in vitro endothelialization, could offer a solution to this problem. A potential minimally invasive source of patient autologous endothelium is endothelial colony-forming cells (ECFCs), endothelial-like outgrowth products of circulating progenitors. While ECFCs respond to shear stress similar to mature endothelial cells (ECs), their response to luminal topographic micropatterning (TMP), a biomaterial modification with the potential to flow-independently, enhance the attachment, migration, gene expression, and function of mature ECs, remains unstudied. In this study, case-matched carotid endothelial cells (CaECs) and blood-derived ECFCs are statically cultured on polyurethane substrates with micropatterned pitches (pitch = peak to peak distance) ranging from 3-to 14 μm. On all pattern pitches tested, both CaECs and ECFCs showed significant and robust alignment to the angle of the micropatterns. Using a novel cell-by-cell image analysis technique, it was found that actin fibers similarly and significantly aligned to the angle of micropatterned features on all pitches tested. Microtubules analyzed through the same novel approach showed significant alignment on most pitches examined, with a greater variation in fiber angle overall. Interestingly, only CaECs showed significant cellular elongation, and notably to a lower degree than previously seen either in vivo due to flow or in vitro due to spatial growth restriction micropatterning, but consistent with earlier studies of TMP. Neither cell type displayed any significant micropattern-driven changes in the expression of KLF-2 or the downstream adhesion molecules it regulates. These results demonstrate that TMP flow-independently affects ECFC morphology, but that alignment alone is insufficient to drive protective changes in EC and ECFC function.

Dataset Information

Endothelial colony-forming cells from preterm infants are increased and more susceptible to hyperoxia.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Endothelial colony-forming cells from preterm infants are increased and more susceptible to hyperoxia.

Similar Datasets

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