Cellular phenotype switching and microvesicles

Abstract

Cell phenotype alteration by cell-derived vesicles presents a new aspect for consideration of cell fate. Accumulating data indicates that vesicles from many cells interact with or enter different target cells from other tissues, altering their phenotype toward that of the cell releasing the vesicles. Cells may be changed by direct interactions, transfer of cell surface receptors or epigenetic reprogramming via transcriptional regulators. Induced epigenetic changes appear to be stable and result in significant functional effects. These data force a reconsideration of the cellular context in which transcription regulates the proliferative and differentiative fate of tissues and suggests a highly plastic cellular system, which might underlay a relatively stable tissue system. The capacity of marrow to convert to non-hematopoietic cells related to vesicle cross-communication may underlie the phenomena of stem cell plasticity. Additionally, vesicles have promise in the clinical arenas of disease biomarkers, tissue restoration and control of neoplastic cell growth.

Figure 1. Cell-derived vesicles and “stem cell plasticity”

Vesicle release from a pulmonary epithelial cell (blue cell) is augmented by cellular injury. Vesicles are consumed by a marrow-derived stem cell (yellow cell) which later assumes phenotypic and functional characteristics of a pulmonary epithelial cell.

Figure 2. Vesicle-induced epigenetic alteration

Cell-derived vesicles appear capable of transferring the essential genetic phenotype of one cell to another. They may do so by a variety of mechanisms, including the transfer of mRNA, microRNA and protein-based transcription factors, which results in epigenetic alteration of target cells.

Figure 3. A model of stem cell biology

In this model, virtually any cell, given the appropriate phase of cell cycle and external influence, including interactions with cell-derived vesicles, could become a stem cell.