scholarly journals Magnetic Nanocomposite Hydrogels for Tissue Engineering: Design Concepts and Remote Actuation Strategies to Control Cell Fate

ACS Nano ◽  
2021 ◽  
Author(s):  
Alberto Pardo ◽  
Manuel Gómez-Florit ◽  
Silvia Barbosa ◽  
Pablo Taboada ◽  
Rui M. A. Domingues ◽  
...  
Polymers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1016 ◽  
Author(s):  
Géraldine Rohman ◽  
Credson Langueh ◽  
Salah Ramtani ◽  
Jean-Jacques Lataillade ◽  
Didier Lutomski ◽  
...  

Due to their elastomeric behavior, polyurethane-based scaffolds can find various applications in soft-tissue engineering. However, their relatively inert surface has to be modified in order to improve cell colonization and control cell fate. The present study focuses on porous biodegradable scaffolds based on poly(ester-urea-urethane), functionalized concomitantly to the scaffold elaboration with low-molecular-weight (LMW) fucoidan; and their bio-activation with platelet rich plasma (PRP) formulations with the aim to promote cell response. The LMW fucoidan-functionalization was obtained in a very homogeneous way, and was stable after the scaffold sterilization and incubation in phosphate-buffered saline. Biomolecules from PRP readily penetrated into the functionalized scaffold, leading to a biological frame on the pore walls. Preliminary in vitro assays were assessed to demonstrate the improvement of scaffold behavior towards cell response. The scaffold bio-activation drastically improved cell migration. Moreover, cells interacted with all pore sides into the bio-activated scaffold forming cell bridges across pores. Our work brought out an easy and versatile way of developing functionalized and bio-activated elastomeric poly(ester-urea-urethane) scaffolds with a better cell response.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yildiz Koca ◽  
Benjamin E. Housden ◽  
William J. Gault ◽  
Sarah J. Bray ◽  
Marek Mlodzik

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notch, belonging to the Nfacet class, reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the epidermal growth factor receptor (EGFR), to fine-tune the activity of EGFR signaling. Consistently, the loss-of-function defects of Nfacet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam-dependent transcription.


Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 670-673 ◽  
Author(s):  
Hao Yuan Kueh ◽  
Ameya Champhekar ◽  
Stephen L. Nutt ◽  
Michael B. Elowitz ◽  
Ellen V. Rothenberg

Regulatory gene circuits with positive-feedback loops control stem cell differentiation, but several mechanisms can contribute to positive feedback. Here, we dissect feedback mechanisms through which the transcription factor PU.1 controls lymphoid and myeloid differentiation. Quantitative live-cell imaging revealed that developing B cells decrease PU.1 levels by reducing PU.1 transcription, whereas developing macrophages increase PU.1 levels by lengthening their cell cycles, which causes stable PU.1 accumulation. Exogenous PU.1 expression in progenitors increases endogenous PU.1 levels by inducing cell cycle lengthening, implying positive feedback between a regulatory factor and the cell cycle. Mathematical modeling showed that this cell cycle–coupled feedback architecture effectively stabilizes a slow-dividing differentiated state. These results show that cell cycle duration functions as an integral part of a positive autoregulatory circuit to control cell fate.


Author(s):  
Lucy LeBlanc ◽  
Nereida Ramirez ◽  
Jonghwan Kim

AbstractHippo effectors YAP and TAZ control cell fate and survival through various mechanisms, including transcriptional regulation of key genes. However, much of this research has been marked by conflicting results, as well as controversy over whether YAP and TAZ are redundant. A substantial portion of the discordance stems from their contradictory roles in stem cell self-renewal vs. differentiation and cancer cell survival vs. apoptosis. In this review, we present an overview of the multiple context-dependent functions of YAP and TAZ in regulating cell fate decisions in stem cells and organoids, as well as their mechanisms of controlling programmed cell death pathways in cancer.


2021 ◽  
pp. ASN.2020081177
Author(s):  
Jingping Yang ◽  
Difei Zhang ◽  
Masaru Motojima ◽  
Tsutomu Kume ◽  
Qing Hou ◽  
...  

BackgroundTranscriptional programs control cell fate, and identifying their components is critical for understanding diseases caused by cell lesion, such as podocytopathy. Although many transcription factors (TFs) are necessary for cell-state maintenance in glomeruli, their roles in transcriptional regulation are not well understood.MethodsThe distribution of H3K27ac histones in human glomerulus cells was analyzed to identify superenhancer-associated TFs, and ChIP-seq and transcriptomics were performed to elucidate the regulatory roles of the TFs. Transgenic animal models of disease were further investigated to confirm the roles of specific TFs in podocyte maintenance.ResultsSuperenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Integration of transcriptome and cistrome data of FOXC1/2 in mice resolved transcriptional regulation in podocyte maintenance. FOXC1/2 regulated differentiation-associated transcription in mature podocytes. In both humans and animal models, mature podocyte injury was accompanied by deregulation of FOXC1/2 expression, and FOXC1/2 overexpression could protect podocytes in zebrafish.ConclusionsFOXC1/2 maintain podocyte differentiation through transcriptional stabilization. The genome-wide chromatin resources support further investigation of TFs’ regulatory roles in glomeruli transcription programs.


Author(s):  
Christopher A. Gosnell ◽  
Scarlett R. Miller

Engineering design idea-generation sessions often result in dozens, if not hundreds, of ideas. These ideas must be quickly evaluated and filtered in order to select a few candidate concepts to move forward in the design process. While creativity is often stressed in the conceptual phases of design, it receives little attention in these later phases — particularly during concept selection. This is largely because there are no methods for quickly rating or identifying worthwhile creative concepts during this process. Therefore, the purpose of this study was to develop and test a novel method for evaluating the creativity and feasibility of design concepts and compare this method to gold standards in our field. The SCAT method employed in this paper uses word selections and semantic similarity to quickly and effectively evaluate candidate concepts for their creativity and feasibility. This method requires little knowledge of the rating process by the evaluator. We tested this method with 10 engineering designers and three different design tasks. Our results revealed that SCAT ratings can be used as a proxy for measuring design concepts but there are modifications that could enhance its utility. This work contributes to our understanding of how to evaluate creativity after idea generation and provides a framework for further research in this field.


Author(s):  
Emma Carley ◽  
Rachel K. Stewart ◽  
Abigail Zieman ◽  
Iman Jalilian ◽  
Diane. E. King ◽  
...  

AbstractWhile the mechanisms by which chemical signals control cell fate have been well studied, how mechanical inputs impact cell fate decisions are not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmission to the nucleus regulates epidermal cell fate. Using a molecular biosensor, we find that tension on the nucleus through Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes requires integrin engagement in undifferentiated epidermal stem cells, and is released during differentiation concomitant with decreased tension on A-type lamins. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiation in vivo and in vitro and influence accessibility of epidermal differentiation genes, suggesting that force transduction from engaged integrins to the nucleus plays a role in maintaining keratinocyte progenitors. This work reveals a direct mechanotransduction pathway capable of relaying adhesion-specific signals to regulate cell fate.


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