scholarly journals Polymeric sheet actuators with programmable bioinstructivity

2020 ◽  
Vol 117 (4) ◽  
pp. 1895-1901 ◽  
Author(s):  
Zijun Deng ◽  
Weiwei Wang ◽  
Xun Xu ◽  
Oliver E. C. Gould ◽  
Karl Kratz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Shape Change ◽  
Cell Lineage ◽  
Fundamental Principle ◽  
Signaling Cascades ◽  
Specific Cell ◽  
Polymer Actuator ◽  
Intracellular Ca ◽  
Functional Biomaterials ◽  
Biochemical Signals

Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSCs). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSCs are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.

scholarly journals Timing of induction of cardiomyocyte differentiation for in vitro cultured mesenchymal stem cells: a perspective for emergenciesThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).

2009 ◽  
Vol 87 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Zeynep Tokcaer-Keskin ◽  
A. Ruchan Akar ◽  
Fatma Ayaloglu-Butun ◽  
Ece Terzioglu-Kara ◽  
Serkan Durdu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Troponin I ◽  
Cell Lineage ◽  
Specific Cell ◽  
Cardiomyocyte Differentiation ◽  
Time Period ◽  
Intracellular Ca ◽  
Colony Forming Capacity

Mesenchymal stem cells (MSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and cardiomyocytes. Several established methods are presently available for in vitro isolation of MSCs from bone marrow. However, the duration necessary to culture them can be a major handicap to cell-based therapies needed for such urgent cardiovascular conditions as acute myocardial infarction and acute hindlimb ischemia. The best timing of cardiomyocyte differentiation induction after MCS isolation and expansion is still an unresolved issue. Our goal was to investigate the possibility of obtaining functional cardiomyocytes from rat MSC within a shorter time period. We examined MSCs’ colony-forming capacity, CD90 and CD34 immunoreactivity during the 14 days of culturing. Cardiomyocyte differentiation was induced by 5-azacytidine. Immunohistochemic staining, together with intracellular Ca2+ measurement experiments, revealed that MSCs do not differentiate into any specific cell lineage but show the characteristics of MSCs on both the 9th and 14th days of the culture. To check the potential for differentiation into cardiomyocytes, experiments with caffeine application and depolarization with KCl were performed. The cells possessed some of the specific biochemical features of contracting cells, with slightly higher capacities on the 14th day. Cells from 9th and 14th days of the culture that were treated with 5-azacytidine had a higher expression of cardiac-specific markers such as troponin I, α-sarcomeric actin, and MEF2D compared with the control groups. This study illustrates that it is possible to get functional cardiomyocytes from in vitro MSC culture in a shorter time period than previously achieved. This reduction in time may provide emergency cases with access to cell-based therapies that may have previously been unavailable.

scholarly journals Analyzing Impetus of Regenerative Cellular Therapeutics in Myocardial Infarction

2020 ◽  
Vol 9 (5) ◽  
pp. 1277 ◽  
Author(s):  
Ming-Long Chang ◽  
Yu-Jui Chiu ◽  
Jian-Sing Li ◽  
Khoot-Peng Cheah ◽  
Hsiu-Hu Lin
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Cardiac Fibroblasts ◽  
Cell Lineage ◽  
Specific Cell ◽  
Paracrine Factors ◽  
Differentiation Potential ◽  
Cell Based Therapy ◽  
Organ Specific ◽  
Made In

Both vasculature and myocardium in the heart are excessively damaged following myocardial infarction (MI), hence therapeutic strategies for treating MI hearts should concurrently aim for true cardiac repair by introducing new cardiomyocytes to replace lost or injured ones. Of them, mesenchymal stem cells (MSCs) have long been considered a promising candidate for cell-based therapy due to their unspecialized, proliferative differentiation potential to specific cell lineage and, most importantly, their capacity of secreting beneficial paracrine factors which further promote neovascularization, angiogenesis, and cell survival. As a consequence, the differentiated MSCs could multiply and replace the damaged tissues to and turn into tissue- or organ-specific cells with specialized functions. These cells are also known to release potent anti-fibrotic factors including matrix metalloproteinases, which inhibit the proliferation of cardiac fibroblasts, thereby attenuating fibrosis. To achieve the highest possible therapeutic efficacy of stem cells, the other interventions, including hydrogels, electrical stimulations, or platelet-derived biomaterials, have been supplemented, which have resulted in a narrow to broad range of outcomes. Therefore, this article comprehensively analyzed the progress made in stem cells and combinatorial therapies to rescue infarcted myocardium.

scholarly journals Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo

2020 ◽  
Vol 21 (12) ◽  
pp. 4350
Author(s):  
Iria Samper Agrelo ◽  
Jessica Schira-Heinen ◽  
Felix Beyer ◽  
Janos Groh ◽  
Christine Bütermann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Neural Stem Cells ◽  
Cell Lineage ◽  
Underlying Mechanism ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Specific Cell ◽  
Secretome Analysis

Mesenchymal stem cell (MSC)-secreted factors have been shown to significantly promote oligodendrogenesis from cultured primary adult neural stem cells (aNSCs) and oligodendroglial precursor cells (OPCs). Revealing underlying mechanisms of how aNSCs can be fostered to differentiate into a specific cell lineage could provide important insights for the establishment of novel neuroregenerative treatment approaches aiming at myelin repair. However, the nature of MSC-derived differentiation and maturation factors acting on the oligodendroglial lineage has not been identified thus far. In addition to missing information on active ingredients, the degree to which MSC-dependent lineage instruction is functional in vivo also remains to be established. We here demonstrate that MSC-derived factors can indeed stimulate oligodendrogenesis and myelin sheath generation of aNSCs transplanted into different rodent central nervous system (CNS) regions, and furthermore, we provide insights into the underlying mechanism on the basis of a comparative mass spectrometry secretome analysis. We identified a number of secreted proteins known to act on oligodendroglia lineage differentiation. Among them, the tissue inhibitor of metalloproteinase type 1 (TIMP-1) was revealed to be an active component of the MSC-conditioned medium, thus validating our chosen secretome approach.

scholarly journals Reorganization of Metabolism during Cardiomyogenesis Implies Time-Specific Signaling Pathway Regulation

2021 ◽  
Vol 22 (3) ◽  
pp. 1330
Author(s):  
María Julia Barisón ◽  
Isabela Tiemy Pereira ◽  
Anny Waloski Robert ◽  
Bruno Dallagiovanna
Keyword(s):  
Stem Cells ◽  
Embryoid Body ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Cardiac Differentiation ◽  
Lipid Homeostasis ◽  
Specific Cell ◽  
Regulatory Pathways ◽  
Time Specific

Understanding the cell differentiation process involves the characterization of signaling and regulatory pathways. The coordinated action involved in multilevel regulation determines the commitment of stem cells and their differentiation into a specific cell lineage. Cellular metabolism plays a relevant role in modulating the expression of genes, which act as sensors of the extra-and intracellular environment. In this work, we analyzed mRNAs associated with polysomes by focusing on the expression profile of metabolism-related genes during the cardiac differentiation of human embryonic stem cells (hESCs). We compared different time points during cardiac differentiation (pluripotency, embryoid body aggregation, cardiac mesoderm, cardiac progenitor and cardiomyocyte) and showed the immature cell profile of energy metabolism. Highly regulated canonical pathways are thoroughly discussed, such as those involved in metabolic signaling and lipid homeostasis. We reveal the critical relevance of retinoic X receptor (RXR) heterodimers in upstream retinoic acid metabolism and their relationship with thyroid hormone signaling. Additionally, we highlight the importance of lipid homeostasis and extracellular matrix component biosynthesis during cardiomyogenesis, providing new insights into how hESCs reorganize their metabolism during in vitro cardiac differentiation.

scholarly journals Topography: A Biophysical Approach to Direct the Fate of Mesenchymal Stem Cells in Tissue Engineering Applications

Nanomaterials ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 2070 ◽  
Author(s):  
Xingli Cun ◽  
Leticia Hosta-Rigau
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Surface Topography ◽  
Cell Lineage ◽  
Specific Cell ◽  
Multipotent Stem Cells ◽  
Nano Fabrication ◽  
Tremendous Amount ◽  
Biophysical Approach

Tissue engineering is a promising strategy to treat tissue and organ loss or damage caused by injury or disease. During the past two decades, mesenchymal stem cells (MSCs) have attracted a tremendous amount of interest in tissue engineering due to their multipotency and self-renewal ability. MSCs are also the most multipotent stem cells in the human adult body. However, the application of MSCs in tissue engineering is relatively limited because it is difficult to guide their differentiation toward a specific cell lineage by using traditional biochemical factors. Besides biochemical factors, the differentiation of MSCs also influenced by biophysical cues. To this end, much effort has been devoted to directing the cell lineage decisions of MSCs through adjusting the biophysical properties of biomaterials. The surface topography of the biomaterial-based scaffold can modulate the proliferation and differentiation of MSCs. Presently, the development of micro- and nano-fabrication techniques has made it possible to control the surface topography of the scaffold precisely. In this review, we highlight and discuss how the main topographical features (i.e., roughness, patterns, and porosity) are an efficient approach to control the fate of MSCs and the application of topography in tissue engineering.

scholarly journals Ionomycin Ameliorates Hypophosphatasia via Rescuing Alkaline Phosphatase Deficiency-mediated L-type Ca2+ Channel Internalization in Mesenchymal Stem Cells

2019 ◽  
Author(s):  
Bei Li ◽  
Xiaoning He ◽  
Zhiwei Dong ◽  
Kun Xuan ◽  
Wei Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Cell Lineage ◽  
Bone Homeostasis ◽  
Loss Of Function ◽  
Channel Trafficking ◽  
Lineage Differentiation ◽  
Promising Therapeutic Approach ◽  
Intracellular Ca

AbstractLoss-of-function mutations in ALPL result in hypophosphatasia (HPP), an inborn error of metabolism that causes skeletal mineralization defect. In adults, main clinical involvement includes early loss of primary or secondary teeth, osteoporosis, bone pain, chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused reduction of intracellular Ca2+ influx resulting in osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse BMSCs. To elevate intracellular level of calcium in bone marrow mesenchymal stem cells (BMSCs) by ionomycin treatment rescues the osteoporotic phenotype in alpl+/- mice and BMSC-specific (Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL is required to maintain intracellular Ca2+ influx by regulating L-type Ca2+ channel trafficking via binding to the α2δ subunits, which regulates the internalization of L-type Ca2+ channel. Decreased Ca2+ flux inactivates Akt/GSK3β/β-catenin signaling pathway that regulates lineage differentiation of BMSCs. This study identifies a previous unknown role of ectoenzyme ALPL in maintenance of calcium channel trafficking to keep stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channel by ionomycin treatment may be a promising therapeutic approach for adult HPP patients.One Sentence SummaryALP regulates internalization of L-Type Ca2+ Channel of BMSCs in Hypophosphatasia.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

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