A Novel View of Umbilical Cord Blood Versus Maternal Peripheral Blood — Evidence for an Increase in the Number of Circulating Stem Cells on Both Sides of the Fetal–Maternal Circulation Barrier.

Background. Umbilical cord blood (UCB) is a rich source of stem cells, including hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitors cells (EPCs), and very small embryonic-like stem cells (VSELs). We envision that these cells are mobilized into UCB in response to hypoxia and increases in the levels of pro-mobilizing factors released in response to delivery stress. We have hypothesized that these stem cells may play a role in repairing tissue/organ injuries that occur in the newborn child after delivery and that mobilization of these cells into newborn peripheral blood could be a kind of autologous, physiological stem cell therapy that all newborns experience after delivery. Aim of the study. Interestingly, in contrast to the intensive research on stem cells present in UCB, parallel research on stem cells released into maternal blood has been lacking. This is despite the fact that, like the newborn child, the mother is exposed to several types of injuries related to delivery, such as damage due to passage of the fetus through the reproductive tract, hypoxia, and the release of pro-mobilizing cytokines and bioactive lipids. Hypothesis. We hypothesized that the number of circulating stem cells also increases in the maternal circulation due to stress related to delivery as part of an autologous regeneration mechanism.Materials and Methods. To evaluate the possibility of a parallel increase in the number of circulating stem cells in the maternal circulation, we analyzed the number of circulating HSCs, MSCs, EPCs, and VSELs in maternal peripheral blood 12-24 hours before and 24 hours after normal delivery (n=17). Specifically, we analyzed CD133⁺/Lin^-/CD45⁺ or CD34⁺/Lin^-/CD45⁺ cells enriched for hematopoietic SCs (HSCs), the CD34⁺/CD133⁺/KDR⁺ population of endothelial progenitor cells (EPCs), the CD45^-/CD105⁺/CD90⁺/CD29⁺ population of mesenchymal SCs (MSCs), and the CD34⁺ and CD133⁺ populations of Lin⁻CD45⁻ very small embryonic-like stem cells (VSELs). We also employed standard clonogenic assays to enumerate the number of hematopoietic progenitors circulating in maternal blood. Results. We observed that the number of HSCs, MSCs, EPCs, VSELs and clonogenic progenitors increases significantly in maternal blood at 24 hours after normal delivery (n=17). Conclusions. Based on this observation, we propose that delivery stress is associated with an increase in the number of circulating stem cells, not only on the fetal side but also on the maternal side of the fetal-maternal circulatory barrier. We propose that, most likely, the increase in the number of circulating stem cells in maternal blood indicates that these cells play a role in repairing small tissue/organ injuries that occur in the mother's body due to delivery. Currently, we are determining whether these changes correspond with other clinical parameters, such as the extent of the mother's internal injuries or the Apgar status of the newborn child, and whether there are changes in the number of circulating stem cells in maternal blood after planned C-sections. We propose that this phenomenon of maternally circulating stem cells could potentially be harnessed to accelerate the recovery of the mother following delivery.