Smooth Muscle  - Development and Stem Cells

Embryonic and Postnatal Development of the Smooth Muscle:

The vascular smooth muscle cells (SMCs) which populate different vessels arise from several lineages within the developing embryo. Recent fate mapping analysis primarily performed in mouse and in surgical removal/and or transplantation experiments in chick, show that distinct embryonic populations which arise from germ layer derivatives, such as lateral plate/paraxial mesoderm and cranial (head) neural crest, contribute to the smooth muscle components of the blood vasculature. It was also shown that at postnatal and adult stages, stem cells from specific niches can contribute to normal and damaged smooth muscle tissue.  As such, molecular signatures of the different smooth muscle cell origins are unique and respond rather differently to the same secreted cues.

The smooth muscles in the pharyngeal arch arteries are contributed by a sub cranial neural crest (CNC) population termed the cardiac neural crest. These cells migrate from the anterior part of the embryo (e.g., head region), accumulate and differentiate at the walls of these vessels to become part of the vascular system. The neural crest contributes SMCs to the ascending and arch portions of the aorta, the ductus arteriosus, the innominate and right subclavian arteries, as well as the right and left common carotid arteries.

The secondary heart field contributes SMCs to the elongating aorta and pulmonary trunk. The growth of these vessels results in two kinds of closures in the arterial pole, namely the myocardial junction with secondary heart field-derived SMCs, and secondary heart field SMCs with neural crest-derived SMCs.

During development, the dorsal aorta is developed in a close proximity to the somites. Various works have shown that both sclerotome and myotome progenitor cells within the somite contribute to the SMCs of the descending aorta in a region-specific manner. Specific progenitor cells termed mesangioblasts (which give rise to skeletal, smooth muscle and other mesenchymal cell types), originating from the hypaxial dermomyotome, has also been shown to contribute, to some extent, to the developing aorta.  

In the coronary vasculature of the heart, the proepicardium cells (i.e., early cells derived from the splanchnic mesoderm) are the progenitor cells of the coronary smooth muscles.

Several different sources of progenitor and stem cells have been indicated to contribute to SMCs of various vessel walls in the adult, including a side population (SP) from the intima–media region and progenitor cells from the adventitia. Other sources of multipotential cells that have been reported to differentiate into SMCs include human adipose tissue, multipotential cardiac progenitor cells, amniotic fluid-derived mesenchymal stem cells, bone marrow–derived stromal cells, and follicular dendritic cells.

Anatomical Structure and Function of the Smooth Muscle:

Smooth muscle is an involuntary, non-striated muscle which can contract and relax but differs from skeletal and cardiac muscle in both structure and functions.  Smooth muscles are categorized as single unit (unitary) or multiunit smooth muscle. Within single-unit smooth muscle type, which are the most common smooth muscles (e.g., blood vasculature ), the autonomic nervous system innervates a single cell within a bundle and the action potential is spread by gap junctions to neighboring cells, allowing the entire bundle to contract as a syncytium. In contrast, in multiunit smooth muscles (e.g., iris), individual cells are innervated, to allow fine control and gradual response.

Smooth muscle is found within the walls of blood vessels (i.e., vascular smooth muscle) of large (i.e., aorta and pulmonary trunk) and small arteries, arterioles and veins. They are also found in lymphatic vessels, urinary bladder, uterus, reproductive tract, gastrointestinal tract (GI tract), respiratory tract, skin, ciliary muscle, and iris of the eye.

The vascular smooth muscle cells (SMCs) are highly specialized cells which contract and regulate blood vessel diameter, blood pressure, and blood flow distribution.  Incorporation of SMCs or SMC-like pericytes within blood vessels is necessary for proper vascular maturation during embryogenesis, along with vascular repair in the adult.