Mesenchymal stem cells as all-round supporters in a normal and neoplastic microenvironment

Abstract

Mesenchymal stem cells (MSC) represent a heterogeneous population exhibiting stem cell-like properties which are distributed almost ubiquitously among perivascular niches of various human tissues and organs. Organismal requirements such as tissue damage determine interdisciplinary functions of resident MSC including self-renewal, migration and differentiation, whereby MSC support local tissue repair, angiogenesis and concomitant immunomodulation. However, growth of tumor cells and invasion also causes local tissue damage and injury which subsequently activates repair mechanisms and consequently, attracts MSC. Thereby, MSC exhibit a tissue-specific functional biodiversity which is mediated by direct cell-to-cell communication via adhesion molecule signaling and by a tightly regulated exchange of a multifactorial panel of cytokines, exosomes, and micro RNAs. Such interactions determine either tumor-promoting or tumor-inhibitory support by MSC. Moreover, fusion with necrotic/apoptotic tumor cell bodies contributes to re-program MSC into an aberrant phenotype also suggesting that tumor tissue in general represents different types of neoplastic cell populations including tumor-associated stem cell-like cells. The present work summarizes some functional characteristics and biodiversity of MSC and highlights certain controversial interactions with normal and tumorigenic cell populations, including associated modulations within the MSC microenvironment.

Human Mesenchymal Stroma/Stem Cells Exchange Membrane Proteins and Alter Functionality During Interaction with Different Tumor Cell Lines

“…7B). This observation indicated spontaneous cell fusion between a mesenchymal stem cell and a corresponding tumor cell as previously described for MDA-MB-231 breast cancer cell hybrids [16,26]. Further characterization of such a chimeric/hybrid cell clone revealed CD90 expression by about 90.4% compared with a parental expression of 97.1% in MSC but undetectable levels of less than 0.1% in parental MDA-MB-231 cells ( Table 1).…”

“…Thus, MSC can be detected within the adipose breast tissue and the fibroglandular tissue of the breast, thereby forming close vicinity to normal human mammary epithelial cells (HMEC) and to breast cancer cells within the tumor microenvironment [14][15][16]. Likewise, MSC are also present in tissues of the ovary and their tumorigenic counterparts.…”

Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-β/SMAD2 Pathway During Wound Healing

“…MSCbased therapies have been shown to induce a complex process of interactions among numerous types of cells, components of the extracellular matrix, and signaling molecules after injury. Such therapies have been reported to promote wound healing, maintain cutaneous homeostasis, and reduce scar formation [27,28]. Most previous studies were aimed at deciphering the mechanism of the healing promoting effects of MSC-based therapies.…”

In Vitro Characterization of the Molecular Machinery Regulating Umbilical Cord Blood Mesenchymal Stem Cell Angiogenesis: A Step Towards Multipotent Stem Cell Therapy for Vascular Regeneration

“…When implanted with fibrin in a myocardial infarct model, UCBMSCs also organized into vascular networks, reduced scar size and increased the blood vessel-occupied area in the subjacent myocardium [18]. The findings presented here contribute to a better understanding of the molecular machinery regulating angiogenesis by multipotent MSCs [43]. Notably, we highlight that Egr-3 is commonly involved regulating mature EC and multipotent MSC angiogenesis through a central PKCα/MAPK/ERK via; this knowledge may be applied to increase efficacy of cell therapies against human diseases with vascular deficit, including cardiac alterations of ischemic origin.…”