Abstract
Branching morphogenesis (BrM), an essential step for salivary gland development, requires epithelial-mesenchymal interactions. BrM is impaired when the surrounding mesenchyme is detached from the salivary epithelium during the pseudoglandular stage. It is believed that the salivary mesenchyme is indispensable for BrM, however, an extracellular matrix gel with exogenous EGF can be used as a substitute for the mesenchyme during BrM in the developing salivary epithelium. Stem/progenitor cells isolated from salivary glands in humans and rodents can be classified as mesenchymal stem cell-like, bone-marrow-derived, duct cell-like, and embryonic epithelium-like cells. Salivary-gland-derived progenitor (SGP) cells isolated from duct-ligated rats, mice, and swine submandibular glands share similar characteristics, including intracellular laminin and α6β1-integrin expression, similar to the embryonic salivary epithelia during the pseudoglandular stage. Progenitor cells also isolated from human salivary glands (human SGP cells) having the same characteristics differentiate into hepatocyte-like cells when transplanted into the liver. Similar to the dissociated embryonic salivary epithelium, human SGP cells aggregate to self-organize into branching organ-like structures on Matrigel plus exogenous EGF. These results suggest the possibility that tissue stem cells organize rudiment-like structures, and the embryonic cells that organize into whole tissues during development are preserved even in adult tissues.
Highlights
Salivary glands are small digestive organs that have a wide variety of functions and vary greatly in the dominant cell type in acini as well as cytodifferentiation of the acinar cells depending on the major glands
Salivary glands synthesize and secrete a large variety of polypeptides including growth factors that have systemic effects. Both epidermal growth factor (EGF) and nerve growth factor (NGF) isolation from mouse salivary gland are especially well known since researchers studying the topic were awarded a Nobel prize [1]
We discuss the evaluation of the characteristics of representative stem/ progenitor cells isolated from adult salivary glands such as mesenchymal stem cell-like cells (SGSCs), bone-marrowderived cells (BMDCs), c-kit-positive excretory duct cells, intercalated duct (ID) cells, and salivary gland-derived progenitor (SGP) cells
Summary
Salivary glands are small digestive organs that have a wide variety of functions and vary greatly in the dominant cell type in acini as well as cytodifferentiation of the acinar cells depending on the major glands. We discuss the evaluation of the characteristics of representative stem/ progenitor cells isolated from adult salivary glands such as mesenchymal stem cell-like cells (SGSCs), bone-marrowderived cells (BMDCs), c-kit-positive excretory duct cells, intercalated duct (ID) cells, and salivary gland-derived progenitor (SGP) cells. Among these candidates, SGP cells are involved in intracellular laminin production and α6β1integrin expression. We show how human SGP cells could self-organize to constitute rudiment-like structures in culture only with Matrigel plus exogenous EGF. This result suggests the possibility that tissue stem cells are capable of organizing rudiment-like structures
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