Development of goal-directed action selection guided by intrinsic motivations: an experiment with children

Action selection is extremely important, particularly when the accomplishment of competitive tasks may require access to limited motor resources. the spontaneous exploration of the world plays a fundamental role in the development of this capacity, providing subjects with an increasingly diverse set of opportunities to acquire, practice and refine the understanding of action-outcome connection. the computational modeling literature proposed a number of specific mechanisms for autonomous agents to discover and target interesting outcomes: intrinsic motivations hold a central importance among those mechanisms. Unfortunately, the study of the acquisition of action-outcome relation was mostly carried out with experiments involving extrinsic tasks, either based on rewards or on predefined task goals. this work presents a new experimental paradigm to study the effect of intrinsic motivation on action-outcome relation learning and action selection during free exploration of the world. three- and four-year-old children were observed during the free exploration of a new toy: half of them were allowed to develop the knowledge concerning its functioning; the other half were not allowed to learn anything. the knowledge acquired during the free exploration of the toy was subsequently assessed and compared

Functional scaffold for chondrogenic differentiation of human mesenchymal stem cells

L'ingegneria tissutale è un campo multidisciplinare in rapida crescita che si avvale delle scienze fisiche, ingegneristiche e della vita per sviluppare ed ottenere cellule funzionali, tessuti ed organi per riparare, sostituire o migliorare le funzioni biologiche perse a causa di anomalie congenite, traumi, malattie o invecchiamento. Nell’ambito della ricostruzione della cartilagine articolare sono stati fatti notevoli passi in avanti ma la soluzione per il ripristino completo del tessuto sembra ancora essere lontana. Nella prima parte di questo lavoro è stata valutata la capacità di uno scaffold a base di gelatina di indirizzare le ADSCs verso un differenziamento in senso condrogenico. Successivamente, con lo scopo di migliorare il grado differenziamento e diminuire i costi associati all’utilizzo di fattori differenziativi, l’attenzione è stata posta sullo sviluppo di un biomateriale a base di alginato e ioni cobalto in modo da mimare e sfruttare le caratteristiche fisiche della cartilagine piuttosto che il suo intorno chimico. In ultimo, è stato sviluppato un sistema low cost per la produzione di chip microfluidici sfruttabili per la realizzazione di sistemi micrometrici per incapsulazione cellulare.Tissue engineering is an interdisciplinary and multidisciplinary field that aims at the developmentof biological substitutes that restore, mantain, or improve tissue function. Concerning the articular cartilage many improvments were made, but the complete tissue restoration approach still lacking. In the first part of this work, it was evaluated the ability of a gelatin scaffold to promote the condrogenic differentiation of ADSCs. Successively, in order to obtain a low cost sistem, a based alginate/Cobalt scaffold was designed with the aim to take advantage of the physical features of the cartilage tissue. Finally, it was developted a cost effective method to produce microfluidic chips with the aim to obtain micro-systems for cell encapsulation

Calcium/Cobalt Alginate Beads as Functional Scaffolds for Cartilage Tissue Engineering

Articular cartilage is a highly organized tissue with complex biomechanical properties. However, injuries to the cartilage usually lead to numerous health concerns and often culminate in disabling symptoms, due to the poor intrinsic capacity of this tissue for self-healing. Although various approaches are proposed for the regeneration of cartilage, its repair still represents an enormous challenge for orthopedic surgeons. The field of tissue engineering currently offers some of the most promising strategies for cartilage restoration, in which assorted biomaterials and cell-based therapies are combined to develop new therapeutic regimens for tissue replacement. The current study describes the in vitro behavior of human adipose-derived mesenchymal stem cells (hADSCs) encapsulated within calcium/cobalt (Ca/Co) alginate beads. These novel chondrogenesis-promoting scaffolds take advantage of the synergy between the alginate matrix and Co+2 ions, without employing costly growth factors (e.g., transforming growth factor betas (TGF-βs) or bone morphogenetic proteins (BMPs)) to direct hADSC differentiation into cartilage-producing chondrocytes

Performance of Motor Sequences in Children at Heightened vs. Low Risk for ASD: A Longitudinal Study from 18 to 36 Months of Age

Recent research shows that motor difficulties are a prominent component of the behavioral profile of autism spectrum disorder (ASD) and are also apparent from early in development in infants who have an older sibling with ASD (High Risk; HR). Delays have been reported for HR infants who do and who do not receive an eventual diagnosis of ASD. A growing body of prospective studies has focused on the emergence of early motor skills primarily during the first year of life. To date, however, relatively little work has examined motor skills in the second and third years. Thus, the present research was designed to investigate motor performance in object transport tasks longitudinally in HR and LR (Low Risk) children between the ages of 18 and 36 months. Participants (15 HR children and 14 LR children) were observed at 18, 24, and 36 months. Children completed two motor tasks, the Ball Task and the Block Task, each of which included two conditions that varied in terms of the precision demands of the goal action. Kinematic data were acquired via two magneto inertial sensors worn on each wrist. In the Block Task, HR children reached more slowly (i.e., mean acceleration was lower) compared to LR children. This finding is in line with growing evidence of early delays in fine motor skills in HR children and suggests that vulnerabilities in motor performance may persist into the preschool years in children at risk for ASD

The hypoxia-mimetic agent cobalt chloride differently affects human mesenchymal stem cells in their chondrogenic potential

Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1\ue1), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 \uecM. Cell viability, HIF-1\ue1 protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from different sources, in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies

Gelatin crosslinked with dehydroascorbic acid as a novel scaffold for tissue regeneration with simultaneous antitumor activity

A porous scaffold was developed to support normal tissue regeneration in the presence of residual tumor disease. It was prepared by gelatin crosslinked with dehydroascorbic acid (DHA). A physicochemical characterization of the scaffold was carried out. SEM and mercury porosimetry revealed a high porosity and interconnection of pores in the scaffold. Enzymatic degradation provided 56% weight loss in ten days. The scaffold was also evaluated in vitro for its ability to support the growth of normal cells while hindering tumor cell development. For this purpose, primary human fibroblasts and osteosarcoma tumor cells (MG-63) were seeded on the scaffold. Fibroblasts attached the scaffold and proliferated, while the tumor cells, after an initial attachment and growth, failed to proliferate and progressively underwent cell death. This was attributed to the progressive release of DHA during the scaffold degradation and its cytotoxic activity towards tumor cells

The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1α), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 μM. Cell viability, HIF-1α protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from different sources, in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies

Increased MG-63s invasion potential mediated by HFs

During a malignant transformation, the crosstalk between the stroma and the cancer cells is described as a growing network of physical and paracrine signals, and it seems to have a direct influence on the phenotypic, genetic and epigenetic changes that affect the cells (1). In order to invade and metastasize to distant tissues, cancer cells transform themselves via ECM, induce tumor angiogenesis as well as undergo proliferation, detachment, migration, and invasion through secretion of various tumor derived factors (2). In this study we decided to analyze morphological and molecular aspects due to the coexistence between tumor cells MG-63s and fibroblasts HFs, verifying in particular the ability of MG-63s of invasion and microenvironment modulation. Monolayers of co-cultured cells were morphologically analyzed in time-laps by HR-SEM microscopy and a trans-well migration assay was performed over 24 h, 48 h, 72 h, and 96 h. The expression of several proteins, focusing on those involved in cancer cell invasion, inflammatory responses, and angiogenesis (TNF alpha, IL-6, YKL-40, MMP-1, MMP-9, and VEGF) was validated by Western blotting analysis. The images in time-laps for HR - SEM showed that fibroblasts in contact with MG-63 lost their spatial orientation, while the MG-63 quickly reached the confluence advancing towards HF cells, invading their space and overlying them. The increased MG-63s invasion mediated by the coexistence with HFs was confirmed by invasion assays in transwell co-culture. The protein levels of TNF-alpha, IL-6, YKL-40 and VEGF confirmed that tumor cells can regulate the development of a “tumor-stroma” via the aberrant expression of growth factors in the stromal compartment. Our results showed how tumor-stroma interactions play a significant role in tumor development and progression

A synergic effect of alginate and hypoxia-inducing ions on chondrogenic differentiation in adipose derived mesenchymal stem cells

Cartilage is a highly organized tissue with complex biomechanical properties, but since it has a poor intrinsic capacity of self-healing, injuries at this site usually lead to several problems, often ending in disabling symptoms. Although, different approach- es have been proposed, even now cartilage repair represents a great challenge for orthopaedic surgeons (1, 2). One of the promising approach is given from tissue engineering, employing the combination of biomaterials and cell therapy to develop new therapeutic strategies. In this paper, we describe the behaviour of human adipose derived mesenchymal stem cells encapsulated into Ca/Co alginate beads as potential chondrogenic inducing biomaterial tacking advance on the synergy between alginate matrix and Co+2 ions without employing other expensive growth factors such as TGFbs or BMPs. Cells were cultured up to 3 weeks into alginate beads at different Ca/Co ratio, Calcein/Ethidium assay was performed to evaluate cell viability, light, and transmis- sion electron microscopy were carried out to check the cells behaviour. The expression of chondrogenic markers such as sox9, collagen type II, and versican was investigated by Real Time PCR. The expression of hif1mRNA was investigated to check the capability of Co+2 ions to induce a chemical hypoxia. Results showed an high cell viability at high Ca/Co ratio value of alginate beads. Real Time PCR data reveal a different cells behaviour on chondrogenic marker expression. In conclusion, the synergic effect of alginate and Co+2 ions can represent a valid strategy for chondrogenic differentiation of stem cells

A synergic effect of alginate and hypoxia-inducing ions on chondrogenic differentiation in adipose derived mesenchymal stem cells

Cartilage is a highly organized tissue with complex biomechanical properties, but since it has a poor intrinsic capacity of self-healing, injuries at this site usually lead to several problems, often ending in disabling symptoms. Although, different approach- es have been proposed, even now cartilage repair represents a great challenge for orthopaedic surgeons (1, 2). One of the promising approach is given from tissue engineering, employing the combination of biomaterials and cell therapy to develop new therapeutic strategies. In this paper, we describe the behaviour of human adipose derived mesenchymal stem cells encapsulated into Ca/Co alginate beads as potential chondrogenic inducing biomaterial tacking advance on the synergy between alginate matrix and Co+2 ions without employing other expensive growth factors such as TGFbs or BMPs. Cells were cultured up to 3 weeks into alginate beads at different Ca/Co ratio, Calcein/Ethidium assay was performed to evaluate cell viability, light, and transmis- sion electron microscopy were carried out to check the cells behaviour. The expression of chondrogenic markers such as sox9, collagen type II, and versican was investigated by Real Time PCR. The expression of hif1mRNA was investigated to check the capability of Co+2 ions to induce a chemical hypoxia. Results showed an high cell viability at high Ca/Co ratio value of alginate beads. Real Time PCR data reveal a different cells behaviour on chondrogenic marker expression. In conclusion, the synergic effect of alginate and Co+2 ions can represent a valid strategy for chondrogenic differentiation of stem cells