Current Stem Cell Research & Therapy - Volume 14, Issue 5, 2019

Aldehyde dehydrogenase (ALDH) is an enzyme that participates in important cellular mechanisms as aldehyde detoxification and retinoic acid synthesis; moreover, ALDH activity is involved in drug resistance, a characteristic of cancer stem cells (CSCs). Even though ALDH is found in stem cells, CSCs and progenitor cells, this enzyme has been successfully used to identify and isolate cell populations with CSC properties from several tumor origins. ALDH is allegedly involved in cell differentiation through its product, retinoic acid. However, direct or indirect ALDH inhibition, using specific inhibitors or retinoic acid, has shown a reduction in ALDH activity, along with the loss of stem cell traits, reduction of cell proliferation, invasion, and drug sensitization. For these reasons, ALDH and retinoic acid are promising therapeutic targets. This review summarizes the current evidence for ALDH as a CSCs marker in solid tumors, as well as current knowledge about the functional roles of ALDH in CSCs. We discuss the controversy of ALDH activity to maintain CSC stemness, or conversely, to promote cell differentiation. Finally, we review the advances in using ALDH inhibitors as anti-cancer drugs.

Cancer Stem Cells (CSCs) constitute a subpopulation at the top of the tumor cell hierarchy that contributes to tumor heterogeneity and is uniquely capable of seeding new tumors. Because of their biological properties, CSCs have been pointed out as therapeutic targets for the development of new therapies against breast cancer. The identification of drugs that selectively target breast CSCs requires a clear understanding of their biological functions and the experimental methods to evaluate such hallmarks. Herein, we review the methods to study breast CSCs properties and discuss their value in the preclinical evaluation of CSC-targeting drugs.

Breast cancer stem cells (BCSCs) are a small population of tumor-initiating cells that express stem cell-associated markers. In recent years, their properties and mechanisms of regulation have become the focus of intense research due to their intrinsic resistance to conventional cancer therapies. This review describes breast cancer stem cell origin, signaling pathways involved in self-renewal, such as Wnt, Notch and Hedgehog, biomarkers linked to stemness, and the role of sex steroid hormones in BCSC regulation.

Cancer Stem Cells (CSC) generally constitute a minor cellular population within tumors that exhibits some capacities of normal Stem Cells (SC). The existence of CSC, able to self-renew and differentiate, influences central aspects of tumor biology, in part because they can continue tumor growth, give rise to metastasis, and acquire drug and radioresistance, which open new avenues for therapeutics. It is well known that SC constantly interacts with their niche, which includes mesenchymal cells, extracellular ligands, and the Extra Cellular Matrix (ECM). These interactions regularly lead to homeostasis and maintenance of SC characteristics. However, the exact participation of each of these components for CSC maintenance is not clear, as they appear to be context- or cell-specific. In the recent past, surface cellular markers have been fundamental molecular tools for identifying CSC and distinguishing them from other tumor cells. Importantly, some of these cellular markers have been shown to possess functional roles that affect central aspects of CSC. Likewise, some of these markers can participate in regulating the interaction of CSC with their niche, particularly the ECM. We focused this review on the molecular mechanisms of surface cellular markers commonly employed to identify CSC, highlighting the signaling pathways and mechanisms involved in CSC-ECM interactions, through each of the cellular markers commonly used in the study of CSC, such as CD44, CD133, CD49f, CD24, CXCR4, and LGR5. Their presence does not necessarily implicate them in CSC biology.

CSCs are a population of self-renewing and tumor repopulating cells that have been observed in hematologic and solid tumors and their presence contributes to the development of drug resistance. The failure to eliminate CSCs with conventional therapy is one of major obstacles in the successful treatment of cancer. Several mechanisms have been described to contribute to CSCs chemoresistance properties that include the adoption of drug-efflux pumps, drug detoxification pathways, changes in metabolism, improved DNA repair mechanisms, and deregulated survival and pro-apoptotic pathways. Thus, CSCs are therefore an attractive target to develop new anti-cancer therapies.

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

Exosomes, small extracellular vesicles with diameters of 40-100nm, are generated through the fusion of multivessel with plasma membrane and secreted by a variety of living cells. Exosomes contain lipid bilayer membrane and releasable functionally active proteins, mRNA and microRNAs (miRNAs). This article reviews the latest progress of researches on exosomes in diseases that lead to infertility.

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.