Harnessing human adipose-derived stromal cell chondrogenesis in vitro for enhanced endochondral ossification.

Endochondral ossification (ECO), the major ossification process during embryogenesis and bone repair, involves the formation of a cartilaginous template remodelled into a functional bone organ. Adipose-derived stromal cells (ASC), non-skeletal multipotent progenitors from the stromal vascular fraction (SVF) of human adipose tissue, were shown to recapitulate ECO and generate bone organs in vivo when primed into a hypertrophic cartilage tissue (HCT) in vitro. However, the reproducibility of ECO was limited and the major triggers remain unknown.

Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms.

Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes.

Comparison of Emotional Processing Between Patients with Substance Use Disorder and Those with Dual Diagnosis: Relationship with Severity of Dependence and Use During Treatment.

This study analyzed, in a Spanish sample, the differences in emotional processing in patients diagnosed with substance use disorder (SUD) and patients with a dual diagnosis (DD), and tested whether alterations in emotional regulation were related to the severity of dependence and consumption during treatment. A descriptive follow-up study was conducted with 88 adult outpatients (83% men) who were receiving treatment for alcohol and cocaine SUD. Of the sample, 43.

Engineering of immunoinstructive extracellular matrices for enhanced osteoinductivity.

The increasing recognition of the contribution of the immune system to activate and prime regeneration implies that tissue engineering strategies and biomaterials design should target regulation of early immunological processes. We previously proposed the cell-based engineering and devitalization of extracellular matrices (ECMs) as a strategy to generate implant materials delivering custom-defined signals. Here, in the context of bone regeneration, we aimed at enhancing the osteoinductivity of such ECMs by enriching their immunomodulatory factors repertoire.

Toward 3D Bioprinting of Osseous Tissue of Predefined Shape Using Single-Matrix Cell-Bioink Constructs.

Engineering living bone tissue of defined shape on-demand has remained a challenge. 3D bioprinting (3DBP), a biofabrication process capable of yielding cell constructs of defined shape, when combined with developmental engineering can provide a possible path forward. Through the development of a bioink possessing appropriate rheological properties to carry a high cell load and concurrently yield physically stable structures, printing of stable, cell-laden, single-matrix constructs of anatomical shapes is realized without the need for fugitive or support phases.

Mini- and macro-scale direct perfusion bioreactors with optimized flow for engineering 3D tissues.

Bioreactors enabling direct perfusion of cell suspensions or culture media through the pores of 3D scaffolds have long been used in tissue engineering to improve cell seeding efficiency as well as uniformity of cell distribution and tissue development. A macro-scale U-shaped bioreactor for cell culture under perfusion (U-CUP) has been previously developed. In that system, the geometry of the perfusion chamber results in rather uniform flow through most of the scaffold volume, but not in the peripheral regions.

Coping strategies in parents of children with disabilities: A case-control study.

Introduction: The aim of this article is to determine whether there are differences in the coping strategies of parents of children with disabilities (autism spectrum disorder or other disabilities) and children without disabilities, in reference to the most stressful situation they have experienced with their child in the last year.

Method: To conduct the study, a purposive sample selection based on case-control characteristics was carried out, in which a total sample of 170 participants was recruited. Participants were assigned, according to their characteristics, to the group of parents of children without disabilities, with ASD or with other disabilities.

Biomimetic human bone marrow tissues: models to study hematopoiesis and platforms for drug testing.

We propose an 3D culture system combining perfusion bioreactors, scaffolds and human primary cells to engineer fully-humanized, biomimetic and customizable bone marrow tissues. This system could serve as a model to investigate human hematopoietic stem cell niches, but also as a drug testing platform for pharmaceutical research and patient-personalized medicine.

A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.

The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sympathetic noradrenergic nerve fibers decrease bone mass, but the role of cholinergic signaling in bone has remained largely unknown. Here, we describe that early postnatally, a subset of sympathetic nerve fibers undergoes an interleukin-6 (IL-6)-induced cholinergic switch upon contacting the bone.

Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.

The sympathetic nervous system has been evolutionary selected to respond to stress and activates haematopoietic stem cells via noradrenergic signals. However, the pathways preserving haematopoietic stem cell quiescence and maintenance under proliferative stress remain largely unknown. Here we found that cholinergic signals preserve haematopoietic stem cell quiescence in bone-associated (endosteal) bone marrow niches.

Engineering of fully humanized and vascularized 3D bone marrow niches sustaining undifferentiated human cord blood hematopoietic stem and progenitor cells.

Hematopoietic stem and progenitor cells (HSPCs) are frequently located around the bone marrow (BM) vasculature. These so-called perivascular niches regulate HSC function both in health and disease, but they have been poorly studied in humans due to the scarcity of models integrating complete human vascular structures. Herein, we propose the stromal vascular fraction (SVF) derived from human adipose tissue as a cell source to vascularize 3D osteoblastic BM niches engineered in perfusion bioreactors.

Culturing patient-derived malignant hematopoietic stem cells in engineered and fully humanized 3D niches.

Human malignant hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) niches, which remain challenging to explore due to limited in vivo accessibility and constraints with humanized animal models. Several in vitro systems have been established to culture patient-derived HSPCs in specific microenvironments, but they do not fully recapitulate the complex features of native bone marrow. Our group previously reported that human osteoblastic BM niches (O-N), engineered by culturing mesenchymal stromal cells within three-dimensional (3D) porous scaffolds under perfusion flow in a bioreactor system, are capable of maintaining, expanding, and functionally regulating healthy human cord blood-derived HSPCs.

Manufacturing of Human Tissues as off-the-Shelf Grafts Programmed to Induce Regeneration.

Design criteria for tissue-engineered materials in regenerative medicine include robust biological effectiveness, off-the-shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex logistic. Here, a conceptual shift based on the manufacturing of devitalized human hypertrophic cartilage (HyC), as cell-free material inducing bone formation by recapitulating the developmental process of endochondral ossification, is reported.

Evolutionary Perspective and Expression Analysis of Intronless Genes Highlight the Conservation of Their Regulatory Role.

The structure of eukaryotic genes is generally a combination of exons interrupted by intragenic non-coding DNA regions (introns) removed by RNA splicing to generate the mature mRNA. A fraction of genes, however, comprise a single coding exon with introns in their untranslated regions or are intronless genes (IGs), lacking introns entirely. The latter code for essential proteins involved in development, growth, and cell proliferation and their expression has been proposed to be highly specialized for neuro-specific functions and linked to cancer, neuropathies, and developmental disorders.

The Autonomic Nervous System Pulls the Strings to Coordinate Circadian HSC Functions.

As for many other adult stem cells, the behavior of hematopoietic stem and progenitor cells (HSPCs) is subjected to circadian regulatory patterns. Multiple HSPC functions, such as proliferation, differentiation or trafficking exhibit time-dependent patterns that require a tight coordination to ensure daily blood cell production. The autonomic nervous system, together with circulating hormones, relay circadian signals from the central clock-the suprachiasmatic nucleus in the brain-to synchronize HSC niche physiology according to light/darkness cycles.

Extracellular Matrices to Modulate the Innate Immune Response and Enhance Bone Healing.

Extracellular matrices (ECMs) have emerged as promising off-the-shelf products to induce bone regeneration, with the capacity not only to activate osteoprogenitors, but also to influence the immune response. ECMs generated starting from living cells such as mesenchymal stromal cells (MSCs) have the potential to combine advantages of native tissue-derived ECMs (e.g.

Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging.

Hematopoietic stem cells (HSCs) residing in the bone marrow (BM) accumulate during aging but are functionally impaired. However, the role of HSC-intrinsic and -extrinsic aging mechanisms remains debated. Megakaryocytes promote quiescence of neighboring HSCs.

Dual cholinergic signals regulate daily migration of hematopoietic stem cells and leukocytes.

Hematopoietic stem and progenitor cells (HSPCs) and leukocytes circulate between the bone marrow (BM) and peripheral blood following circadian oscillations. Autonomic sympathetic noradrenergic signals have been shown to regulate HSPC and leukocyte trafficking, but the role of the cholinergic branch has remained unexplored. We have investigated the role of the cholinergic nervous system in the regulation of day/night traffic of HSPCs and leukocytes in mice.

Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance.

Hematopoietic stem and progenitor cells (HSPCs) tightly couple maintenance of the bone marrow (BM) reservoir, including undifferentiated long-term repopulating hematopoietic stem cells (LT-HSCs), with intensive daily production of mature leukocytes and blood replenishment. We found two daily peaks of BM HSPC activity that are initiated by onset of light and darkness providing this coupling. Both peaks follow transient elevation of BM norepinephrine and TNF secretion, which temporarily increase HSPC reactive oxygen species (ROS) levels.

A Linked List-Based Algorithm for Blob Detection on Embedded Vision-Based Sensors.

Blob detection is a common task in vision-based applications. Most existing algorithms are aimed at execution on general purpose computers; while very few can be adapted to the computing restrictions present in embedded platforms. This paper focuses on the design of an algorithm capable of real-time blob detection that minimizes system memory consumption.

BMSCs and hematopoiesis.

Recent discoveries have significantly expanded our previous knowledge about the role of bone marrow mesenchymal stem cells (BMSCs) in hematopoiesis. BMSCs and their derivatives modulate blood production and immunity at different levels but a prominent role has emerged for BMSCs in the regulation of hematopoietic stem and progenitor cells (HSPCs). Additionally, BMSC-like cells regulate B and T cell lymphopoiesis and also probably myelopoiesis.

Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis.

Estrogens are potent regulators of mature hematopoietic cells; however, their effects on primitive and malignant hematopoietic cells remain unclear. Using genetic and pharmacological approaches, we observed differential expression and function of estrogen receptors (ERs) in hematopoietic stem cell (HSC) and progenitor subsets. ERα activation with the selective ER modulator (SERM) tamoxifen induced apoptosis in short-term HSCs and multipotent progenitors.

Failure to find symmetry in pigeons after multiple exemplar training.

Background: An experiment with pigeons was conducted for 46 months in order to test the multiple-exemplar training (MET) hypothesis of symmetry derivation. According to this hypothesis, symmetry is progressively derived after an extensive training of multiple examples of direct and inverse relations among arbitrary stimuli.

Method: Four pigeons were given extensive training in direct (e.

The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.

Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions.

The influence of the parents' educational level and participants' age in the derivation of equivalence-equivalence.

Background: The objective of this work was the study of analogical reasoning from the perspective of the equivalence-equivalence phenomenon.

Method: The variables studied consisted of the age of the participants and the educational level of the parents, in relation to performance on a reasoning task. The task utilized a sample size of 64 participants and an instrument based on conditional discriminations using the matching-to-sample procedure.