Frontiers in Stem Cell and Regenerative Medicine Research: Volume 2

Atta-ur-Rahman, Shazia Anjum

• Publisher: Bentham Science Publishers
• Year: 2016
• ISBN:
  9781681081830
• Topic: Biological Sciences
• Subtopic: Cell Biology
• Index: Biological Sciences

Stem cell and regenerative medicine research is a hot area of research which promises to change the face of medicine as it will be practiced in the years to come. Challenges in 21st century to combat diseases such as cancer, Alzheimer and related diseases may well be addressed employing stem cell therapies and tissue regeneration. Frontiers in Stem Cell and Regenerative Medicine Research is essential reading for researchers seeking updates in stem cell therapeutics and regenerative medicine.
The second volume of this series features reviews on several key topics in this field including cardiac regeneration strategies, induced pluripotent stem cell therapeutics, stem cell therapy for peripheral nerve and cutaneous injuries, dental tissue regeneration, the potential of stem cell differentiation into ovarian cells and much more.

Biological and Therapeutic Implications of Cancer Stem Cells

CANCER PATHOGENESIS: STOCHASTIC VS. CANCER STEM CELL MODEL

The majority of the cancers are composed of a variety of cell types with distinct genetic, epigenetic and morphologic features. Thus, tumors are a group of transformed cells with different phenotypes and distinct functional properties. Clinically, tumors from different patients often exhibit significant heterogeneity in terms of morphology, cell surface markers, genetic lesions, cell proliferation rate, and response to therapy. Therefore, it is necessary to understand the molecular and cellular basis of the heterogeneity to design effective and selective therapeutic approaches. Currently, this heterogeneity can be explained based on two broad models: cancer stem cell hypothesis (or hierarchy cancer model) and the clonal evolution model (or stochastic model).

Until 1970s, the cancer field was dominated by the clonal evolution model (Fig. 1b), a concept whereby each cell within a tumor has equal potential in acquiring stepwise, genetic and/or epigenetic changes, conferring growth advantages and generating new tumors [1, 2]. The intrinsic differences within tumor cells may be caused by stochastic genetic [1] and epigenetic [3] changes acquired over time. Heterogeneity can also be explained by extrinsic mechanisms in which different microenvironments within a tumor confer phenotypic and functional differences upon cancer cells in different locations [4, 5]. According to the clonal evolution cancer model, cancer initiation takes place once multiple mutations occur in a random single cell, acquiring a selective growth advantage over adjacent normal cells. As cancer progresses, genetic instability and uncontrolled proliferation allow the generation of transformed cells with additional genetic alterations and hence new behavioral characteristics. Alternatively, the new mutations may provide a growth advantage over the other cancer cells such as resistance to therapies and insensitivity to apoptotic signals [1]. Therefore, this clonal progression is an evolutionary process that is driven by selection and expansion of adapted subclones in a Darwinian fashion [6]. According to this model, all tumor cells contribute to tumor maintenance and regeneration with differing capacities. This model is supported by histopathological evidence of disease progression and metastasis [7 - 11], genetic single-cell analysis [12 - 18] and immunophenotype [19].

The clonal evolution already begins at an early stage of the disease and multiple subclones are already established at diagnosis without previous therapy. These subclones have different capabilities regarding survival, proliferation, therapy resistance and tumorigenicity. Once the therapy is started, those drug-sensitive subclones will be eradicated leading to a pharmacologic selection of drug-resistant ones, which can outgrow after a certain delay and cause the relapse. After the majority of the subclones are eliminated by the therapy, the clonal evolution and competition within the remaining resistant subclones start again producing a novel heterogeneous mixture of subclones that may resemble the primary tumor bulk population. With every treatment round, developmental bottlenecks are created leading to a clonal selection process, which in the end results in the selection of highly drug resistant and aggressive subclones. According to this model, a successful therapy will need to eradicate all subclones within the tumor as any can eventually acquire the tumorigenic capacity. Thus, cancer drugs might target specific signaling pathways highly similarly dysregulated in every transformed cell within the tumor.

The cancer stem cell (CSC) model, also known as the hierarchy model, holds that the growth and progression of cancers are driven by a distinctive subpopulation of cancer stem cells, and the tumor is a caricature of normal tissue development [20] (Fig. 1a). Therefore, cancer stem cells share with their normal counterparts (normal stem cells) their self-renewal capacity and the differentiation potential. Consequently, CSCs can not only maintain themselves, but also differentiate into non-CSC transformed cells that constitute the majority of tumor cells. The first experimental evidence that only a subpopulation of cancer cells has tumorigenic capacity was shown in murine lymphoid leukemia [21], providing experimental evidences of self-renewal capacity of cancer cells. Decades after,...

Table of contents

• Welcome
• Table Of Contents
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• PREFACE
• Contribution of Stem Cells to Dental Tissue Regene-ration: Isolation, Function, and Application
• Epidermal Stem Cells and their Use in Regenerative Applications for Severe Cutaneous Injuries
• Biological and Therapeutic Implications of Cancer Stem Cells
• Role of Stem Cells in Heart Regeneration
• Differentiation Potential of Stem Cells into Ovarian Cells
• Challenges and Opportunities in the Development of Induced Pluripotent Stem Cell Therapeutics
• Cell Cycle and Cell Cycle Regulators in the Process of Development, Pluripotency, Differentiation, and Reprogramming
• Effect of Microenvironment Modulation on Stem Cell Therapy for Peripheral Nerve Injury
• Transplantation of Umbilical Cord Blood Cells for Patients with Neonatal Hypoxic-Ischemic Encephalopathy and Cerebral Palsy: From Preclinical Studies to Ongoing Clinical Trials
• Stem Cells for Treatment of Articular Cartilage Defects and Osteoarthritis