Saima Rajabali

Lung injury in preterm neonates: the role and therapeutic potential of stem cells.

Continuous improvements in perinatal care have allowed the survival of ever more premature infants, making the task of protecting the extremely immature lung from injury increasingly challenging. Premature infants at risk of developing chronic lung disease or bronchopulmonary dysplasia (BPD) are now born at the late canalicular stage of lung development, just when the airways become juxtaposed to the lung vasculature and when gas-exchange becomes possible. Readily available strategies, including improved antenatal management (education, regionalization, steroids, and antibiotics), together with exogenous surfactant and exclusive/early noninvasive ventilatory support, will likely decrease the incidence/severity of BPD over the next few years. Nonetheless, because of the extreme immaturity of the developing lung, the extent to which disruption of lung growth after prematurity and neonatal management lead to an earlier or more aggravated decline in respiratory function in later life is a matter of concern. Consequently, much more needs to be learned about the mechanisms of lung development, injury, and repair. Recent insight into stem cell biology has sparked interest for stem cells to repair damaged organs. This review summarizes the exciting potential of stem cell-based therapies for lung diseases in general and BPD in particular.

Functional Differences Between Placental Micro- and Macrovascular Endothelial Colony-Forming Cells

Alterations in the development of the placental vasculature can lead to pregnancy complications, such as preeclampsia. Currently, the cause of preeclampsia is unknown, and there are no specific prevention or treatment strategies. Further insight into the placental vasculature may aid in identifying causal factors. Endothelial colony‐forming cells (ECFCs) are a subset of endothelial progenitor cells capable of self‐renewal and de novo vessel formation in vitro. We hypothesized that ECFCs exist in the micro‐ and macrovasculature of the normal, term human placenta. Human placentas were collected from term pregnancies delivered by cesarean section (n = 16). Placental micro‐ and macrovasculature was collected from the maternal and fetal side of the placenta, respectively, and ECFCs were isolated and characterized. ECFCs were CD31+, CD105+, CD144+, CD146+, CD14−, and CD45−, took up 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethyl‐indocarbocyanine perchlorate‐labeled acetylated low‐density lipoprotein, and bound Ulex europaeus agglutinin 1. In vitro, macrovascular ECFCs had a greater potential to generate high‐proliferative colonies and formed more complex capillary‐like networks on Matrigel compared with microvascular ECFCs. In contrast, in vivo assessment demonstrated that microvascular ECFCs had a greater potential to form vessels. Macrovascular ECFCs were of fetal origin, whereas microvascular ECFCs were of maternal origin. ECFCs exist in the micro‐ and macrovasculature of the normal, term human placenta. Although macrovascular ECFCs demonstrated greater vessel and colony‐forming potency in vitro, this did not translate in vivo, where microvascular ECFCs exhibited a greater vessel‐forming ability. These important findings contribute to the current understanding of normal placental vascular development and may aid in identifying factors involved in preeclampsia and other pregnancy complications.

The Emerging Role of Stem/Progenitor Cells in Pulmonary Vascular Disease

Pulmonary hypertension is a severe disease characterized by small pulmonary artery obstruction from vascular proliferation and remodeling leading to elevated mean pulmonary arterial pressure, increased pulmonary vascular resistance, right ventricular failure and death. Current treatments include prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors, which largely address mechanisms of endothelial dysfunction that were identified over 2 decades ago. Despite advances in understanding the disease mechanisms and the development of new pharmacological therapies, the prognosis of pulmonary hypertension remains poor. Recent advances in stem cell biology have unraveled the potential of stem/progenitor cells to repair damaged organs and offer the possibility for cell-based treatment for intractable diseases. This review summarizes the emerging role of stem/progenitor cells in the pathophysiology and the treatment of pulmonary hypertension.