Current molecular biology reports最新文献

Purpose of review: The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT.

Recent findings: Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe.

Summary: We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

The tumor microenvironment (TME) has been recognized as an integral component of malignancies in breast and prostate tissues, contributing in confounding ways to tumor progression, metastasis, therapy resistance and disease recurrence. Major components of the TME are immune cells, fibroblasts, pericytes, endothelial cells, mesenchymal stroma/stem cells (MSCs), and extracellular matrix (ECM) components. Herein, we discuss the molecular and cellular heterogeneity within the TME and how this presents unique challenges and opportunities for treating breast and prostate cancers.

This review highlights the recent advances in our understanding of adipocyte contributions to carcinogenesis or cancer disease progression for cancers in the bone.

Purpose: In this review, we aim to describe bone marrow adipose tissue and discuss the soluble adipocyte-derived cytokines (adipokines) or endocrine factors, adipocyte-derived lipids, and the actual or putative juxtacrine signaling between bone marrow adipocytes and tumor cells in the bone marrow. This relationship likely affects tumor cell initiation, proliferation, metastasis, and/or drug resistance.

Recent findings: Bone marrow adipose may affect tumor proliferation, drug resistance, or cancer-induced bone disease and hence may be a new target in the fight against cancer.

Summary: Overall, evidence is mixed regarding the role of bone marrow adipose and adipocytes in cancer progression, and more research in this arena is necessary to determine how these bone marrow microenvironmental cells contribute to malignancies in the marrow to identify novel, potentially targetable pathways.

Purpose: This report defines new concepts of hematopoietic stem cell biology.

Recent findings: We have utilized 3 different approaches which show that long-term repopulating hematopoietic stem cells are actively cycling and always changing phenotype. In addition this is reversible. This indicates that the stem cell cannot be purified by current epitope selection approaches. The vast bulk of hematopoietic stem cells are discarded in different populations when stem cells are purified to lineage negative c-kit positive and Sca-1 positive cells. Studies to define the hematopoietic niche have been largely carried out on these irrelevant purified cells and thus are not definitive. Studies have indicated the presence of baseline stem cells which function during the normal lifetime of mice. Baseline hematopoiesis appears to be run by thousands of relatively short lived clones with limited differentiation capacity. Thus there appear to be two basic hematopoietic stem cell modes; emergency and baseline.

Purpose of review: Progress in stem cell research for blinding diseases over the past decade is now being applied to patients with retinal degenerative diseases and soon perhaps, glaucoma. However, the field still has much to learn about the conversion of stem cells into various retinal cell types, and the potential delivery methods that will be required to optimize the clinical efficacy of stem cells delivered into the eye.

Recent findings: Recent groundbreaking human clinical trials have demonstrated both the opportunities and current limitations of stem cell transplantation for retinal diseases. New progress in developing in vitro retinal organoids, coupled with the maturation of bio-printing technology, and non-invasive high-resolution imaging have created new possibilities for repairing and regenerating the diseased retina and rigorously validating its clinical impact in vivo.

Summary: While promising progress is being made, meticulous clinical trials with cells derived using good manufacturing practice, novel surgical methods, and improved methods to derive all of the neuronal cell types present in the retina will be indispensable for developing stem cell transplantation as a paradigm shift for the treatment of blinding diseases.

Purpose of review: Cancer is a major public health problem worldwide. In aggressive cancers, which are heterogeneous in nature, there exists a paucity of targetable molecules that can be used to predict outcome and response to therapy in patients, especially those in the high risk category with a propensity to relapse following chemotherapy. This review addresses the challenges pertinent to treating aggressive cancer cells with inherent stem cell properties, with a special focus on triple-negative breast cancer (TNBC).

Recent findings: Plasticity underlies the cancer stem cell (CSC) phenotype in aggressive cancers like TNBC. Progenitors and CSCs implement similar signaling pathways to sustain growth, and the convergence of embryonic and tumorigenic signaling pathways has led to the discovery of novel oncofetal targets, rigorously regulated during normal development, but aberrantly reactivated in aggressive forms of cancer.

Summary: Translational studies have shown that Nodal, an embryonic morphogen, is reactivated in aggressive cancers, but not in normal tissues, and underlies tumor growth, invasion, metastasis and drug resistance. Front-line therapies do not inhibit Nodal, but when a combinatorial approach is used with an agent such as doxorubicin followed by anti-Nodal antibody therapy, significant decreases in cell growth and viability occur. These findings are of special interest in the development of new therapeutic interventions that target the stem cell properties of cancer cells to overcome drug resistance and metastasis.

Purpose of review: Ischemic heart disease and stroke lead to the greatest number of deaths worldwide. Despite decreased time to intervention and improvements in the standard of care, 1 out of 5 patients that survive a myocardial infarction (MI) still face long-term chronic heart failure and a 5-year mortality rate of about 50%. Based on their multi-potency for differentiation and paracrine activity, epicardial cells and their derivatives have potential to rescue jeopardized tissue and/or promote cardiac regeneration. Here we review the diagnosis and treatment of MI, basic epicardial cell biology, and potential treatment strategies designed to harness the reparative properties of epicardial cells.

Recent findings: During cardiac development, epicardial cells covering the surface of the heart generate migratory progenitor cells that contribute to the coronary vasculature and the interstitial fibroblasts. Epicardial cells also produce paracrine signals required for myocardial expansion and cardiac growth. In adults with myocardial infarction, epicardial cells and their derivatives provide paracrine factors that affect myocardial remodeling and repair. At present, the intrinsic mechanisms and extrinsic signals that regulate epicardial cell fate and paracrine activity in adults remain poorly understood.

Summary: Human diseases that result in heart failure due to negative remodeling or extensive loss of viable cardiac tissue require new, effective treatments. Improved understanding of epicardial cell function(s) and epicardial-mediated secretion of growth factors, cytokines and hormones during cardiac growth, homeostasis and injury may lead to new ways to treat patients with myocardial infarction.

Purpose of review: The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here.

Recent findings: The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and myofibroblast cells secrete factors that regulate ISC proliferation. Finally, several studies indicate that the microbiome metabolites regulate ISC growth.

Summary: ISC cells can be plastic and integrate a complexity of environmental/niche cues to trigger or suppress proliferation as needed.