Current Stem Cell Reports最新文献

Purpose of review: Neural stem cells (NSCs) have the potential to proliferate and differentiate into functional neurons, heightening their potential use for therapeutic applications. This review explores bioengineered systems which recapitulate NSC niche cell-cell and cell-matrix interactions.

Recent findings: Delivery of NSCs to the cytotoxic injured brain is limited by low cell survival rates post-transplantation and poor maintenance of native niche bioactive components. The use of biomaterial platforms can mimic in vivo the environment of the two germinal areas of the adult brain in which NSCs thrive. An environmental mimic that includes extracellular proteins and moieties, along with appropriate biomechanical cues has recently demonstrated promising results in enhancing neurogenesis, aiding the production of a bioengineered niche.

Summary: Biocomposition, biomechanics, and biostructure can be manipulated through engineered platforms to re-create the biofunctionality of an NSC niche. Upon transplantation and delivery with biomimetic scaffolds, NSCs show potential to promote functional recovery and rebuild neural circuitry post neurological trauma.

The purpose of review: Mobilized peripheral blood is the predominant source of stem and progenitor cells for hematologic transplantation. Successful transplant requires sufficient stem cells of high enough quality to recapitulate lifelong hematopoiesis, but in some patients and normal donors, reaching critical threshold stem cell numbers are difficult to achieve. Novel strategies, particularly those offering rapid mobilization and reduced costs, remains an area of interest.This review summarizes critical scientific underpinnings in understanding the process of stem cell mobilization, with a focus on new or improved strategies for their efficient collection and engraftment.

Recent findings: Studies are described that provide new insights into the complexity of stem cell mobilization. Agents that target new pathways such HSC egress, identify strategies to collect more potent competing HSC and new methods to optimize stem cell collection and engraftment are being evaluated.

Summary: Agents and more effective strategies that directly address the current shortcomings of hematopoietic stem cell mobilization and transplantation and offer the potential to facilitate collection and expand use of mobilized stem cells have been identified.

Purpose of review: The hematopoietic stem cell (HSC) compartment is the cornerstone of a lifelong blood cell production but also contributes to the ability of the hematopoietic system to dynamically respond to environmental challenges. This review summarizes our knowledge about the interaction between HSCs and its inflammatory environment during life and questions how its disruption could affect the health of the hematopoietic system.

Recent findings: The latest research demonstrates the direct role of inflammatory signals in promoting the emergence of the HSCs during development and in setting their steady-state activity in adults. They indicate that inflammatory patho-physiological conditions or immunological history could shape the structure and biology of the HSC compartment, therefore altering its overall fitness.

Summary: Through instructive and/or selective mechanisms, the inflammatory environment seems to provide a key homeostatic signal for HSCs. Although the mechanistic basis of this complex interplay remains to be fully understood, its dysregulation has broad consequences on HSC physiology and the development of hematological diseases. As such, developing experimental models that fully recapitulate a normal basal inflammatory state could be essential to fully assess HSC biology in native conditions.

Purpose of review: Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition characterized by the acquisition of somatic mutations. This concise review explores our current understanding of the mechanisms that influence the development of clonality with aging and its potential malignant and non-malignant clinical implications.

Recent findings: Aging of the hematopoietic system results in phenotypic changes that favor clonal dominance. Cell-extrinsic factors provide additional selective pressures that further shape clonal architecture. Even so, small clones with candidate driver mutations appear to be ubiquitous with age and largely benign in the absence of strong selective pressures. Benign clonal expansion may compensate for the loss of regenerative HSC capacity as we age.

Summary: CHIP is a marker of aging that reflects the biologic interplay between HSC aging and cell-extrinsic factors. The clinical significance of CHIP is highly variable and dependent on clinical context. Distinguishing the causal relationships and confounding factors that regulate clonal behavior will be essential to define the mechanistic role of CHIP in aging and potentially mitigate its clinical consequences.

Purpose of review: Hematopoietic stem cells (HSC) reside in a specialized microenvironment called the HSC niche. While key components of the niche have been known for several years, recent advances have identified several additional cell types that regulate HSC in the bone marrow (BM). Here we review our current understanding of the components and dynamics of the HSC niche.

Recent findings: While the niche has been considered a stable structure, recent advances clearly show that the niche is regulated in a dynamic manner to control HSC traffic and function. Moreover the niche can rapidly remodel in response to insults to the BM in a process controlled by positive and negative regulators.

Summary: Multiple niche cells have been shown to be dynamically regulated by systemic and local signals to influence how the niche controls HSC function. Elucidating how different components of the niche coordinate to orchestrate HSC behavior is essential to understand how the hematopoietic system adjusts blood cell production to the demands of the body.