Comparing Circadian Dynamics in Primary Derived Stem Cells from Different Sources of Human Adult Tissue

Optimising cell/tissue constructs so that they can be successfully accepted and integrated within a host body is essential in modern tissue engineering. To do this, adult stem cells are frequently utilised, but there are many aspects of their environment in vivo that are not completely understood. There is evidence to suggest that circadian rhythms and daily circadian temporal cues have substantial effects on stem cell activation, cell cycle, and differentiation. It was hypothesised that the circadian rhythm in human adult stem cells differs depending on the source of tissue and that different entraining signals exert differential effects depending on the anatomical source. Dexamethasone and rhythmic mechanical stretch were used to synchronise stem cells derived from the bone marrow, tooth dental pulp, and abdominal subcutaneous adipose tissue, and it was experimentally evidenced that these different stem cells differed in their circadian clock properties in response to different synchronisation mechanisms. The more primitive dental pulp-derived stem cells did not respond as well to the chemical synchronisation but showed temporal clock gene oscillations following rhythmic mechanical stretch, suggesting that incorporating temporal circadian information of different human adult stem cells will have profound implications in optimising tissue engineering approaches and stem cell therapies.

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Macrophage modulation of dental pulp stem cell activity during tertiary dentinogenesis

Scientific Reports ◽

10.1038/s41598-020-77161-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Vitor C. M. Neves ◽

Val Yianni ◽

Paul T. Sharpe

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Immune Cells ◽

Dental Pulp ◽

Cell Activation ◽

Cell Activity ◽

Stem Cell Differentiation ◽

Dental Pulp Stem Cell ◽

Anti Inflammatory

AbstractThe interaction between immune cells and stem cells is important during tissue repair. Macrophages have been described as being crucial for limb regeneration and in certain circumstances have been shown to affect stem cell differentiation in vivo. Dentine is susceptible to damage as a result of caries, pulp infection and inflammation all of which are major problems in tooth restoration. Characterising the interplay between immune cells and stem cells is crucial to understand how to improve natural repair mechanisms. In this study, we used an in vivo damage model, associated with a macrophage and neutrophil depletion model to investigate the role of immune cells in reparative dentine formation. In addition, we investigated the effect of elevating the Wnt/β-catenin pathway to understand how this might regulate macrophages and impact upon Wnt receiving pulp stem cells during repair. Our results show that macrophages are required for dental pulp stem cell activation and appropriate reparative dentine formation. In addition, pharmacological stimulation of the Wnt/β-catenin pathway via GSK-3β inhibitor small molecules polarises macrophages to an anti-inflammatory state faster than inert calcium silicate-based materials thereby accelerating stem cell activation and repair. Wnt/β-catenin signalling thus has a dual role in promoting reparative dentine formation by activating pulp stem cells and promoting an anti-inflammatory macrophage response.

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Stem Cell Based Tissue Engineering and Regenerative Medicine: A Review Focusing on Adult Stem Cells

Current Tissue Engineering ◽

10.2174/2211542011201010075 ◽

2012 ◽

Vol 1 (1) ◽

pp. 75-82

Author(s):

Jordan Greenberg ◽

Veronica Fortino ◽

Daniel Pelaez ◽

Herman S. Cheung

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Adult Stem Cells

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Perivascular-Derived Mesenchymal Stem Cells

Journal of Dental Research ◽

10.1177/0022034519862258 ◽

2019 ◽

Vol 98 (10) ◽

pp. 1066-1072 ◽

Cited By ~ 4

Author(s):

V. Yianni ◽

P.T. Sharpe

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Dental Pulp ◽

Molecular Mechanisms ◽

Lineage Tracing ◽

Specific Gene ◽

Genetic Lineage ◽

Differentiation Potential

Cells have been identified in postnatal tissues that, when isolated from multiple mesenchymal compartments, can be stimulated in vitro to give rise to cells that resemble mature mesenchymal phenotypes, such as odontoblasts, osteoblasts, adipocytes, and myoblasts. This has made these adult cells, collectively called mesenchymal stem cells (MSCs), strong candidates for fields such as tissue engineering and regenerative medicine. Based on evidence from in vivo genetic lineage–tracing studies, pericytes have been identified as a source of MSC precursors in vivo in multiple organs, in response to injury or during homeostasis. Questions of intense debate and interest in the field of tissue engineering and regenerative studies include the following: 1) Are all pericytes, irrespective of tissue of isolation, equal in their differentiation potential? 2) What are the mechanisms that regulate the differentiation of MSCs? To gain a better understanding of the latter, recent work has utilized ChIP-seq (chromatin immunoprecipitation followed by sequencing) to reconstruct histone landscapes. This indicated that for dental pulp pericytes, the odontoblast-specific gene Dspp was found in a transcriptionally permissive state, while in bone marrow pericytes, the osteoblast-specific gene Runx2 was primed for expression. RNA sequencing has also been utilized to further characterize the 2 pericyte populations, and results highlighted that dental pulp pericytes are already precommitted to an odontoblast fate based on enrichment analysis indicating overrepresentation of key odontogenic genes. Furthermore, ChIP-seq analysis of the polycomb repressive complex 1 component RING1B indicated that this complex is likely to be involved in inhibiting inappropriate differentiation, as it localized to a number of loci of key transcription factors that are needed for the induction of adipogenesis, chondrogenesis, or myogenesis. In this review, we highlight recent data elucidating molecular mechanisms that indicate that pericytes can be tissue-specific precommitted MSC precursors in vivo and that this precommitment is a major driving force behind MSC differentiation.

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Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function

Science ◽

10.1126/science.aax1694 ◽

2019 ◽

Vol 366 (6466) ◽

pp. 734-738 ◽

Cited By ~ 11

Author(s):

Antoine de Morree ◽

Julian D. D. Klein ◽

Qiang Gan ◽

Jean Farup ◽

Andoni Urtasun ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Messenger Rna ◽

Adult Stem Cells ◽

Alternative Polyadenylation ◽

Quiescent State ◽

Stem Cell Fate ◽

Activation Rate

Adult stem cells are essential for tissue homeostasis. In skeletal muscle, muscle stem cells (MuSCs) reside in a quiescent state, but little is known about the mechanisms that control homeostatic turnover. Here we show that, in mice, the variation in MuSC activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. We further show that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1. Isoforms of the Pax3 messenger RNA that differ in their 3′ untranslated regions are differentially susceptible to regulation by microRNA miR206, which results in varying levels of the Pax3 protein in vivo. These findings highlight a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species.

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Realistic Prospects for Stem Cell Therapeutics

Hematology ◽

10.1182/asheducation-2003.1.398 ◽

2003 ◽

Vol 2003 (1) ◽

pp. 398-418 ◽

Cited By ~ 52

Author(s):

George Q. Daley ◽

Margaret A. Goodell ◽

Evan Y. Snyder

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Cell Biology ◽

Adult Stem Cells ◽

Stem Cell Biology ◽

Cell Therapies ◽

The Media ◽

New Treatment ◽

Definition Of

Abstract Studies of the regenerating hematopoietic system have led to the definition of many of the fundamental principles of stem cell biology. Therapies based on a range of tissue stem cells have been widely touted as a new treatment modality, presaging an emerging new specialty called regenerative medicine that promises to harness stem cells from embryonic and somatic sources to provide replacement cell therapies for genetic, malignant, and degenerative conditions. Insights borne from stem cell biology also portend development of protein and small molecule therapeutics that act on endogenous stem cells to promote repair and regeneration. Much of the newfound enthusiasm for regenerative medicine stems from the hope that advances in the laboratory will be followed soon thereafter by breakthrough treatments in the clinic. But how does one sort through the hype to judge the true promise? Are stem cell biologists and the media building expectations that cannot be met? Which diseases can be treated, and when can we expect success? In this review, we outline the realms of investigation that are capturing the most attention, and consider the current state of scientific understanding and controversy regarding the properties of embryonic and somatic (adult) stem cells. Our objective is to provide a framework for appreciating the promise while at the same time understanding the challenges behind translating fundamental stem cell biology into novel clinical therapies.

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A New Role for Marine Skeletal Proteins in Regenerative Orthopaedics

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.529-530.654 ◽

2012 ◽

Vol 529-530 ◽

pp. 654-659

Author(s):

David W. Green ◽

Matthew Padula ◽

Jerran Santos ◽

Joshua Chou ◽

Bruce Milthorpe ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Marine Sponge ◽

Adult Stem Cells ◽

Cell Activation ◽

Bone Growth ◽

Early Stage ◽

Organic Matrix ◽

Evolutionary Relatedness ◽

Organic Matrices

Use of ready-made marine skeletons is one of the simplest possible remedies to major problems hindering the future development of regenerative orthopaedics- such as, providing a richness of framework designs and now a potentially rich, accessible source of osteopromotive analogues and biomineralisation proteins. It has already been shown that coral and marine sponge skeletons can support self-sustaining musculoskeletal tissues and that extracts of spongin collagen and nacre seashell organic matrices promote bone mineralisation. This should not be surprising given that the pivotal biomineralisation proteins, which orchestrate bone morphogenesis are also found in the earliest calcifying marine organisms. This is because they are representatives of the first molecular components established for calcification, morphogenesis and wound healing. In support of this notion, it has emerged that BMP molecules- the main cluster of bone growth factors for human bone morphogenesis- are secreted by endodermal cells into the developing skeleton. In addition, the regenerative signalling proteins, TGF-b and Wnt-prime targets in bone therapeutics- are also present in early marine sponge development and instrumental to stem cell activation in Cnidarians. Based on this match between vertebrate and invertebrate main developmental proteins, we review the nature and extent of this evolutionary relatedness and use it to support the development of a new strategy, which is to mine selected marine origin organic matrices for novel metabolic, signalling and structural proteins/peptides and protein analogues to apply in regenerative orthopaedics, particularly when using adult stem cells. To support such a proposal we show early stage evidence-gathered in our own laboratory- of the presence of fibrinogen fragments and early osteopromotive effects of a coral organic matrix extract on stem cells. In practice the discovery of new osteopromotive and osteo-accelerant protein analogues will require use of traditional chromatography techniques, osteoactivity assays to hone in on potential proteins of significance and advanced proteomic tools to provide accurate sequencing, determine the mechanisms and molecular pathways involved in osteoactivation and determine the efficiency and effectiveness of marine skeleton-derived protein modulation of the stem cell (MSC) proteome. As more analogues are discovered using proteomic tools, skeletal organic matrices may have ever increasing utility for regenerative orthopaedics.

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Adipose Tissue Engineering from Human Adult Stem Cells: Clinical Implications in Plastic and Reconstructive Surgery

Yearbook of Plastic and Aesthetic Surgery ◽

10.1016/s1535-1513(08)70688-x ◽

2008 ◽

Vol 2008 ◽

pp. 224-225

Author(s):

S.H. Miller

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Adipose Tissue ◽

Reconstructive Surgery ◽

Adult Stem Cells ◽

Clinical Implications ◽

Plastic And Reconstructive Surgery ◽

Adipose Tissue Engineering ◽

Human Adult

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Multifunctional silica-coated iron oxide nanoparticles: a facile four-in-one system for in situ study of neural stem cell harvesting

Faraday Discussions ◽

10.1039/c4fd00132j ◽

2014 ◽

Vol 175 ◽

pp. 13-26 ◽

Cited By ~ 15

Author(s):

Yung-Kang Peng ◽

Cathy N. P. Lui ◽

Tsen-Hsuan Lin ◽

Chen Chang ◽

Pi-Tai Chou ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Iron Oxide ◽

Magnetic Resonance ◽

Neural Stem Cells ◽

Neural Stem Cell ◽

Cell Therapies ◽

Bimodal Imaging

Neural stem cells (NSCs), which generate the main phenotypes of the nervous system, are multipotent cells and are able to differentiate into multiple cell types via external stimuli from the environment. The extraction, modification and re-application of NSCs have thus attracted much attention and raised hopes for novel neural stem cell therapies and regenerative medicine. However, few studies have successfully identified the distribution of NSCs in a live brain and monitored the corresponding extraction processes both in vitro and in vivo. To address those difficulties, in this study multi-functional uniform nanoparticles comprising an iron oxide core and a functionalized silica shell (Fe3O4@SiO2(FITC)-CD133, FITC: a green emissive dye, CD133: anti-CD133 antibody) have been strategically designed and synthesized for use as probe nanocomposites that provide four-in-one functionality, i.e., magnetic agitation, dual imaging (both magnetic resonance and optical) and specific targeting. It is shown that these newly synthesized Fe3O4@SiO2(FITC)-CD133 particles have clearly demonstrated their versatility in various applications. (1) The magnetic core enables magnetic cell collection and T2 magnetic resonance imaging. (2) The fluorescent FITC embedded in the silica framework enables optical imaging. (3) CD133 anchored on the outermost surface is demonstrated to be capable of targeting neural stem cells for cell collection and bimodal imaging.

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