Review

Abstract

Oocytes play a pivotal role in the cycle of human life. As we discuss here, after emerging from germline stem cells in the fetus, they grow in a follicular niche in which development is harmonized for timely ovulation and hormone secretion after puberty. Most human oocytes have poor developmental competence and are peculiarly vulnerable to chromosomal malsegregation, especially as women pass the optimal years of fertility and may begin to turn to assisted reproductive technologies (ARTs) and egg donation. Research needs to focus on the molecular factors involved and the environmental niche required for optimal development of oocytes, with the aim of increasing their numbers and quality for ARTs, since these are the factors that so often limit human fertility.

Authors

Roger Gosden, Bora Lee

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Abstract

The ability to create new functional cardiomyocytes is the holy grail of cardiac regenerative medicine. From studies using model organisms, new insights into the fundamental pathways that drive heart muscle regeneration have begun to arise as well as a growing knowledge of the distinct families of multipotent cardiovascular progenitors that generate diverse lineages during heart development. In this Review, we highlight this intersection of the “pregenerative” biology of heart progenitor cells and heart regeneration and discuss the longer term challenges and opportunities in moving toward a therapeutic goal of regenerative cardiovascular medicine.

Authors

B. Alexander Yi, Oliver Wernet, Kenneth R. Chien

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Abstract

Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of somatic cells through the exogenous expression of transcription factors. These cells, just like embryonic stem cells, are likely to have a major impact on regenerative medicine, because they self-renew and retain the potential to be differentiated into all cell types of the human body. In this Review, we describe the current state of iPS cell technology, including approaches by which they are generated and what is known about their biology, and discuss the potential applications of these cells for disease modeling, drug discovery, and, eventually, cell replacement therapy.

Authors

Evangelos Kiskinis, Kevin Eggan

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Abstract

Cancer stem cells (CSCs) are a subpopulation of tumor cells that selectively possess tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of nontumorigenic cancer cell progeny through differentiation. As we discuss here, they have been prospectively identified in several human malignancies, and their relative abundance in clinical cancer specimens has been correlated with malignant disease progression in human patients. Furthermore, recent findings suggest that clinical cancer progression driven by CSCs may contribute to the failure of existing therapies to consistently eradicate malignant tumors. Therefore, CSC-directed therapeutic approaches might represent translationally relevant strategies to improve clinical cancer therapy, in particular for those malignancies that are currently refractory to conventional anticancer agents directed predominantly at tumor bulk populations.

Authors

Natasha Y. Frank, Tobias Schatton, Markus H. Frank

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Abstract

Over the last decade, a remarkable number of papers have been published in which the biology of stem cells is introduced with words and phrases such as “promise,” “rapid progress,” and “future therapies.” To separate myth and hype from reality, the articles in this Stem Cells Review series comprise a rich resource on the state of this fast-paced field and provide a balanced perspective on some of the major advances. They recount what the field has achieved over the past decade and where the field is headed. They also highlight the challenges to be faced in translating what is indeed highly promising science into proven therapies that will regenerate and repair diseased tissues.

Authors

George Q. Daley

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Abstract

Discussion of the bioethics of human stem cell research has transitioned from controversies over the source of human embryonic stem cells to concerns about the ethical use of stem cells in basic and clinical research. Key areas in this evolving ethical discourse include the derivation and use of other human embryonic stem cell–like stem cells that have the capacity to differentiate into all types of human tissue and the use of all types of stem cells in clinical research. Each of these issues is discussed as I summarize the past, present, and future bioethical issues in stem cell research.

Authors

Insoo Hyun

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Abstract

Skeletal muscle damaged by injury or by degenerative diseases such as muscular dystrophy is able to regenerate new muscle fibers. Regeneration mainly depends upon satellite cells, myogenic progenitors localized between the basal lamina and the muscle fiber membrane. However, other cell types outside the basal lamina, such as pericytes, also have myogenic potency. Here, we discuss the main properties of satellite cells and other myogenic progenitors as well as recent efforts to obtain myogenic cells from pluripotent stem cells for patient-tailored cell therapy. Clinical trials utilizing these cells to treat muscular dystrophies, heart failure, and stress urinary incontinence are also briefly outlined.

Authors

Francesco Saverio Tedesco, Arianna Dellavalle, Jordi Diaz-Manera, Graziella Messina, Giulio Cossu

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Abstract

Stem cell–based approaches have received much hype as potential treatments for neurodegenerative disorders. Indeed, transplantation of stem cells or their derivatives in animal models of neurodegenerative diseases can improve function by replacing the lost neurons and glial cells and by mediating remyelination, trophic actions, and modulation of inflammation. Endogenous neural stem cells are also potential therapeutic targets because they produce neurons and glial cells in response to injury and could be affected by the degenerative process. As we discuss here, however, significant hurdles remain before these findings can be responsibly translated to novel therapies. In particular, we need to better understand the mechanisms of action of stem cells after transplantation and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment.

Authors

Olle Lindvall, Zaal Kokaia

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Abstract

Enabling stem cell–targeted therapies requires an understanding of how to create local microenvironments (niches) that stimulate endogenous stem cells or serve as a platform to receive and guide the integration of transplanted stem cells and their derivatives. In vivo, the stem cell niche is a complex and dynamic unit. Although components of the in vivo niche continue to be described for many stem cell systems, how these components interact to modulate stem cell fate is only beginning to be understood. Using the HSC niche as a model, we discuss here microscale engineering strategies capable of systematically examining and reconstructing individual niche components. Synthetic stem cell–niche engineering may form a new foundation for regenerative therapies.

Authors

Raheem Peerani, Peter W. Zandstra

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Abstract

Inflammation is the coordinated immune response to harmful stimuli that appear during infections or after tissue damage. Cells of the innate immune system are the central players in mediating inflammatory tissue responses. These cells are equipped with an array of signaling receptors that detect foreign molecular substances or altered endogenous molecules that appear under situations of stress. This review provides an overview of recent progress in elucidating the molecular mechanisms that lead to inflammatory reactions. We discuss the current knowledge of the mechanisms leading to the activation of cytoplasmic, multimolecular protein complexes, termed “inflammasomes,” which regulate the activity of caspase-1 and the maturation and release of IL-1β.

Authors

Andrea Stutz, Douglas T. Golenbock, Eicke Latz

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