Recent investigations have indicated that hematopoietic stem cells (HSCs) have the potential to differentiate into multiple non-blood cell lineages and contribute to the cellular regeneration of various tissues and multiple organs. Most studies to date on HSC potential have examined the adult, focusing on their potential to repair tissue under pathological conditions (e.g., ischemic injury, organ failure). Comparatively little is known about the physiological role of HSCs in normal tissue homeostasis in the adult, and even less of their contribution to organogenesis during prenatal development. This study reports the contribution of blood-borne cells to various organ systems of the developing embryo using a quail-chick parabiosis model. Under these conditions, the developing circulatory systems fuse between ED6-ED8, resulting in free exchange of circulating cells. Cells of quail origin, identified by quail-specific antibodies at ED15, were found in numerous organs of the parabiotic chick embryo. Circulating cells contributed to developing vasculature, where they differentiated into endothelial, smooth muscle, and adventitial tissues. In the heart, differentiation of circulating cells into cardiomyocytes was demonstrated using double immunolabeling for QCPN and sarcomeric actin or myosin. These results were confirmed by intramyocardial injection of quail bone marrow cells that were found to express markers of myocytes, coronary smooth muscle, and epicardium. Experiments using lacZ-transgenic chick embryos for a second positive cellular marker showed that fusion between chick and quail cells was a rare event. These results suggest that during development, multipotent cells are present in the embryonic circulation and home into different organs where they undergo tissue-specific differentiation. Moreover, the demonstration that blood-borne cells contribute to the development of various organs lends credence to claims that hematopoietic stem cells have utility for treating diseased or damaged tissues in the adult.

The extracellular matrix plays a critical role in the development and maintenance of the vertebrate heart. Changes in the accumulation, composition, or organization of the extracellular matrix are known to deleteriously affect heart function. Mast cells are thought to stimulate collagen expression and fibroblast proliferation accompanying fibrosis in some organs; however, the effects of mast cells on the heart interstitium are largely unexplored. The present studies were carried out to determine the effects of mast cells on isolated heart fibroblasts. Several in vitro assays were used including collagen gel contraction to examine the effects of mast cells on the function of isolated fibroblasts. Neonatal heart fibroblasts were cultured either with mast cells, mast cell-conditioned medium, or mast cell extracts, and their ability to contract collagen gels measured. Results from these experiments indicated that mast cells inhibit heart fibroblast migration and contraction of 3-dimensional collagen gels. Further experiments indicated that incubation of neonatal heart fibroblasts with extracts of mast cells altered the expression of collagen, matrix metalloproteases, and matrix receptors of the integrin family. These studies suggest that mast cells play an important role in the regulation of the cardiac interstitial matrix. Further studies are warranted to determine the mechanisms whereby mast cells modulate fibroblast activity.