Advantages of human umbilical vein scaffolds derived from cesarean section vs. vaginal delivery for vascular tissue engineering
Introduction
Bypassing stenoses in coronary arteries requires small caliber grafts with unique properties. In contrast to vascular reconstructions in large-diameter vessels like aorta, the antithrombotic properties of the graft surface as well as its visco-elastic properties are of critical importance. To date, there is no clinically suitable bypass material based on synthetic polymers. Although endothelial seeding greatly improves the patency of, e.g. PTFE grafts [1], the compliance mismatch between grafts and coronary arteries remains to be solved [2]. It is now widely recognized that extracellular matrix (ECM) would make an ideal scaffold for therapeutic applications [3]. De-endothelialized human umbilical vein (HUV) has recently been suggested as a living scaffold for vascular tissue engineering [4]. Umbilical cords are a cheap and abundant source of stem cells and of vascular tissue, with recruitment rates exceeding 60% of all births in an ongoing study [5]. De-endothelialized HUV contain ECM with suitable visco-elastic properties [6] along with fetal smooth muscle cells which can synthesize and remodel ECM. Turning this semi-finished biomaterial into a vascular graft will require two tissue-engineering processes. First, in order to provide a hemocompatible and non-immunogenic surface, endothelial function has to be restored by seeding recipient-derived endothelial cells (EC). Second, the graft has to mature in a pulsatile bioreactor to create a wall structure and EC alignment suitable for the pressure and shear forces of the coronary circulation [7]. The quality of a vessel replacement engineered from umbilical vessels, and the difficulties associated with the engineering process, are likely to depend on the quality of the starting material. Therefore, the current study investigated the influence of the mode of birth on the functional properties of HUV.
The influence of the birth mode on the physiology of neonates has been investigated in several studies. It is generally accepted that delivery by a planned (elective) cesarean section (PCS) is less stressful for the fetus than a spontaneous vaginal delivery (VD). There is a body of evidence that PCS causes less oxidative stress as measured by the levels of lipid peroxidation products [8], [9] and of the antioxidant glutathione [10] in the cord blood. Along the same lines, the levels of the stress indicators cortisol [11], progesterone [12], and norepinephrine [13] as well as the number of CD34+ mononuclear cells [14] in the cord blood are lower after a PCS. This study tried to address the question whether the same differences affect the performance of HUV post partum.
With the exception of PCS, the exact time of birth, and thus the time of umbilical cord sample collection, is difficult to predict. Moreover, a large proportion of births occur at times which are inconvenient for a routine tissue engineering protocol. The situation is aggravated if, as it was the case in the present study, the samples have to be processed outside of the hospitals that provide them. This warranted an investigation whether the quality of HUV depends on the duration of ischemia.
Section snippets
Materials and reagents
Calcein AM was supplied by Molecular Probes (Eugene, OR, USA). Hank's Balanced Salt Solution (HBSS) was purchased from Invitrogen (Carlsbad, CA, USA), and fetal calf serum (FCS) was obtained from PAN (Aidenbach, Germany). All other reagents were of analytical grade and were purchased from Sigma (Taufkirchen, Germany) or from Merck (Darmstadt, Germany).
Subjects and harvesting of umbilical cords
A random and unselected group of pregnant women was recruited for the study [5] when they first reported to the maternity wards in the two
Maternal and sample characteristics
Table 1 shows the maternal characteristics as well as the physiologic parameters of the neonates. All but four births occurred at gestational ages of 37+0 weeks or later. The four pre-term births were distributed evenly between VD and c-sections, and none of these pregnancies was shorter than 35+6 weeks. The duration of pregnancies terminated with a PCS was significantly shorter compared to the VD and ECS groups (ANOVA, p<0.001), and the birth weights of the newborns were lower compared to the
Discussion
To the best of our knowledge this is the first comprehensive study that investigates the impact of the different modes of birth on the function of HUV. Recent advances in tissue engineering [4] have turned HUV into a promising biomaterial. The compliance of HUV was shown to be comparable to human saphenous vein, one of the most common bypass materials [15]. Cryopreserved HUV could be combined with fresh or cryopreserved, recipient-matched ECs [16] and processed in a pulsatile bioreactor to
Conclusion
This study has shown that a simplified sample collection protocol involving a once-per-day pickup does not negatively affect the performance of HUV as a starting material for tissue engineering purposes. The data suggest that vessels obtained from c-sections provide better contractility and superior prostacyclin release rates than those obtained from VDs. In future, attention has to be paid to the mode of delivery when selecting vessels as a biomaterial for vascular tissue engineering.
Acknowledgments
The authors acknowledge the excellent technical assistance of C. Leykauf, S. Bergmann, and K. Bielenberg, as well as the help of the midwives in collecting the cord samples. We are indebted to O. Ortmann (OB/GYN, Klinik für Frauenheilkunde und Geburtshilfe, University of Regensburg) for providing additional umbilical cords. J. Burkhart (Blood Donor Service of the Bavarian Red Cross, Munich, Germany) kindly arranged the sample transports between the participating universities. We thank H.
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- 1
Current address: Department of Cardiothoracic Surgery, Klinikum Krefeld, Krefeld, Germany.
- 2
Current address: Department of Cardiac Surgery, Kerckhoff-Klinik, Bad Nauheim, Germany.