scholarly journals Enhancing Myocardial Repair with CardioClusters

2019 ◽  
Author(s):  
Megan M. Monsanto ◽  
Bingyan J. Wang ◽  
Zach R. Ehrenberg ◽  
Oscar Echeagaray ◽  
Kevin S. White ◽  
...  
Keyword(s):  
Interstitial Cell ◽  
Cell Types ◽  
Interstitial Cells ◽  
Neonatal Rat ◽  
Cellular Interaction ◽  
Cell Populations ◽  
Protective Effects ◽  
Next Generation ◽  
3D Microenvironment

AbstractBackgroundCellular therapy to treat heart failure is an ongoing focus of intense research and development, but progress has been frustratingly slow due to limitations of current approaches. Engineered augmentation of established cellular effectors overcomes impediments, enhancing reparative activity with improved outcomes relative to conventional techniques. Such ‘next generation’ implementation includes delivery of combinatorial cell populations exerting synergistic effects. Concurrent isolation and expansion of three distinct cardiac-derived interstitial cell types from human heart tissue, as previously reported by our group, prompted design of a three-dimensional (3D) structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell losses upon delivery.MethodsThree distinct populations of human cardiac interstitial cells including mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments termed CardioClusters. Biological consequences of CardioCluster formation were assessed by multiple assays including single cells RNA-Seq transcriptional profiling. Protective effects of CardioClusters in vitro were measured using cell culture models for oxidative stress and myocardial ischemia in combination with freshly isolated neonatal rat ventricular myocytes. Long-term impact of adoptively transferred CardioClusters upon myocardial structure and function in a xenogenic model of acute infarction using NODscid mice was assessed over a longitudinal time course of 20-weeks.ResultsCardioCluster design enables control over composite cell types, cell ratios, size, and preservation of structural integrity during delivery. Profound changes for biological properties of CardioClusters relative to constituent parental cell populations include enhanced expression of stem cell-relevant factors, adhesion/extracellular-matrix molecules, and cytokines. The CardioCluster 3D microenvironment maximizes cellular interaction while maintaining a more native transcriptome similar to endogenous cardiac cells. CardioCluster delivery improves cell retention following intramyocardial injection with preservation of long-term cardiac function relative to monolayer-cultured cells when tested in an experimental murine infarction model followed for up to 20 weeks post-challenge. CardioCluster-treated hearts show increases in capillary density, preservation of cardiomyocyte size, and reduced scar size indicative of blunting pathologic infarction injury.ConclusionsCardioClusters are a novel ‘next generation’ development and delivery approach for cellular therapeutics that potentiate beneficial activity and enhance protective effects of human cardiac interstitial cell mixed populations. CardioClusters utilization in this preclinical setting establishes fundamental methodologic and biologic insights, laying the framework for optimization of CardioCluster design to provide greater efficacy in cell-based therapeutic interventions intended to mitigate cardiomyopathic damage.

Aortic Valve Interstitial Cell Viscoelasticity

2007 ◽  
Author(s):  
W. David Merryman ◽  
Paul D. Bieniek ◽  
Farshid Guilak ◽  
Michael S. Sacks
Keyword(s):  
Mechanical Properties ◽  
Aortic Valve ◽  
Recent Work ◽  
Interstitial Cell ◽  
Contractile Response ◽  
Dynamic Environment ◽  
Tissue Level ◽  
Interstitial Cells ◽  
Cell Populations

Long term tissue-level durability of the aortic valve (AV) is maintained by the cell populations residing both in the interstitium and on the epithelium. Due to the dynamic environment in which the AV interstitial cells (AVICs) function, recent work has examined the mechano-dependent, biosynthetic and contractile response of these cells [1–4]. Many idealized assumptions have been made about mechanical properties [1, 4], ECM connectivity [2], and deformations that the AVICs undergo during diastole [3]. These assumptions include that the AVICs are elastic, homogenous materials that deformation in an affine sense with the tissue.

scholarly journals The homeobox gene, TGIF1, is required for chicken ovarian cortical development and generation of the juxtacortical medulla

Development ◽  
2021 ◽  
Author(s):  
Martin Andres Estermann ◽  
Claire Elizabeth Hirst ◽  
Andrew Thomas Major ◽  
Craig Allen Smith
Keyword(s):  
Granulosa Cells ◽  
Interstitial Cell ◽  
Cell Lineage ◽  
Homeobox Gene ◽  
Cell Types ◽  
Surface Epithelium ◽  
Cell Populations ◽  
Supporting Cells ◽  
Homeobox Transcription Factor ◽  
Steroidogenic Cells

During early embryogenesis in amniotic vertebrates, the gonads differentiate into either ovaries or testes. The first cell lineage to differentiate gives rise to the supporting cells; Sertoli cells in males and pre-granulosa cells in females. These key cell types direct the differentiation of the other cell types in the gonad, including steroidogenic cells. The gonadal surface epithelium and the interstitial cell populations are less well studied, and little is known about their sexual differentiation programs. Here, we show the requirement of the homeobox transcription factor gene TGIF1 for ovarian development in the chicken embryo. TGIF1 is expressed in the two principal ovarian somatic cell populations, the cortex and the pre-granulosa cells of the medulla. TGIF1 expression is associated with an ovarian phenotype in estrogen-mediated sex reversal experiments. Targeted mis-expression and gene knockdown indicate that TGIF1 is required, but not sufficient, for proper ovarian cortex formation. In addition, TGIF1 is identified as the first known regulator of juxtacortical medulla development. These findings provide new insights into chicken ovarian differentiation and development, specifically cortical and juxtacortical medulla formation.

scholarly journals Molecular regulation of spermatogonial stem cell renewal and differentiation

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. R169-R187 ◽  
Author(s):  
Juho-Antti Mäkelä ◽  
Robin M Hobbs
Keyword(s):  
Cell Fate ◽  
Control Cell ◽  
Reproductive Function ◽  
Cell Types ◽  
Supporting Cell ◽  
Cell Populations ◽  
Cell Renewal ◽  
Cellular Interactions ◽  
Cell Fate Decisions

The intricate molecular and cellular interactions between spermatogonial stem cells (SSCs) and their cognate niche form the basis for life-long sperm production. To maintain long-term fertility and sustain sufficiently high levels of spermatogenesis, a delicate balance needs to prevail between the different niche factors that control cell fate decisions of SSCs by promoting self-renewal, differentiation priming or spermatogenic commitment of undifferentiated spermatogonia (Aundiff). Previously the SSC niche was thought to be formed primarily by Sertoli cells. However, recent research has indicated that many distinct cell types within the testis contribute to the SSC niche including most somatic cell populations and differentiating germ cells. Moreover, postnatal testis development involves maturation of somatic supporting cell populations and onset of cyclic function of the seminiferous epithelium. The stochastic and flexible behavior of Aundiff further complicates the definition of the SSC niche. Unlike in invertebrate species, providing a simple anatomical description of the SSC niche in the mouse is therefore challenging. Rather, the niche needs to be understood as a dynamic system that is able to serve the long-term reproductive function and maintenance of fertility both under steady-state and during development plus regeneration. Recent data from us and others have also shown that Aundiff reversibly transition between differentiation-primed and self-renewing states based on availability of niche-derived cues. This review focuses on defining the current understanding of the SSC niche and the elements involved in its regulation.

scholarly journals TGIF1 is required for chicken ovarian cortical development and generation of the juxtacortical medulla

2021 ◽  
Author(s):  
Martin Andres Estermann ◽  
Claire E Hirst ◽  
Andrew T Major ◽  
Craig A Smith
Keyword(s):  
Granulosa Cells ◽  
Interstitial Cell ◽  
Ovarian Development ◽  
Cell Lineage ◽  
Cell Types ◽  
Surface Epithelium ◽  
Cell Populations ◽  
Supporting Cells ◽  
Over Expression ◽  
Steroidogenic Cells

During early embryogenesis in amniotic vertebrates, the gonads differentiate into either ovaries or testes. The first cell lineage to differentiate gives rise to the supporting cells; Sertoli cells in males and pre-granulosa cells in females. These key cell types direct the differentiation of the other cell types in the gonad, including steroidogenic cells. The gonadal surface epithelium and the interstitial cell populations are less well studied, and little is known about their sexual differentiation programs. Here, we show the requirement of the transcription factor gene TGIF1 for ovarian development in the chicken embryo. TGIF1 is expressed in the two principal ovarian somatic cell populations, the cortex and the pre-granulosa cells of the medulla. TGIF1 expression is associated with an ovarian phenotype in sex reversal experiments. In addition, targeted over-expression and gene knockdown experiments indicate that TGIF1 is required for proper ovarian cortical formation. TGIF1 is identified as the first known regulator of juxtacortical medulla formation. These findings provide new insights into chicken ovarian differentiation and development, specifically in the process of cortical and juxtacortical medulla formation, a poorly understood area.

Genetic analysis of developmental mechanisms in hydra. VI. Cellular composition of chimera hydra

1979 ◽  
Vol 35 (1) ◽  
pp. 1-15
Author(s):  
T. Sugiyama ◽  
T. Fujisawa
Keyword(s):  
Epithelial Cell ◽  
Genetic Analysis ◽  
Interstitial Cell ◽  
Cell Types ◽  
Interstitial Cells ◽  
Cellular Composition ◽  
Feedback Mechanisms ◽  
Cell Lineages ◽  
Developmental Mechanisms ◽  
Homeostatic Mechanisms

The homeostatic mechanisms that maintain constant cellular ratios in hydra tissue were studied using mutant and chimeric hydra strains. Mutants having abnormal cellular compositions are isolated through sexual inbreeding of wild hydra, as described in previous papers of this series. Chimeric hydra are produced by making use of a strain (nf-I) which lacks interstitial cells, nerve cells and nematocytes in its tissue. Reintroduction of interstitial cells from other strains (both normal and mutant) into nf-I leads to creation of chimeric strains having epithelial cell lineages from one strain (nf-I) and interstitial cell lineages from others. Analyses and comparisons of the cellular compositions of all these strains revealed that the numbers of nerve or interstitial cells in the chimeras were very similar to (statistically significantly correlated with) those in their interstitial cell donors. Since chimeras and their interstitial cell donors share the same interstitial cell lineages, this suggests that interstitial cells or their derivatives (nerves and nematocytes) play major roles in determining the nerve and interstitial cell levels in the hydra tissue. It is suggested that some form of homeostatic feedback mechanisms are probably involved in regulating the levels of these cell types.

Single-cell Profiling Reveal Types of Interstitial Cells in Human and Rat Bladder

2020 ◽  
Author(s):  
Zhenxing Yang ◽  
Ye Gao ◽  
Peilin Liu ◽  
Weisheng Jia ◽  
Zhenqiang Fang ◽  
...  
Keyword(s):  
Single Cell ◽  
Interstitial Cell ◽  
Cell Types ◽  
Interstitial Cells ◽  
Rna Seq ◽  
Urothelial Cells ◽  
Bladder Disease ◽  
Rat Bladder ◽  
Single Cell Profiling ◽  
New Type

Abstract Backgrounds:The mechanism underlying bladder urination pathophysiologies has not been understood yet because the types of interstitial cells present in the bladder are still obscure. Results:Here, we classified the cell types in the bladder without bias using 10x genomics single-cell RNA-seq and identified 35,510 and 19,946 cells from human and rat bladder tissues, respectively. In addition to the major cell clusters including urothelial cells, smooth muscle cells, endothelial cells, neurons, and immune cells, three types of interstitial cells were identified in this study. Fibroblasts and myofibroblasts were shown to occupy large proportions of interstitial cells, located mainly between the epithelial strata and muscle strata. A new type of interstitial cell, Mki67+, which was found both in human and rat bladder tissues, may participate in bladder disease development. Conclusions:Our investigation thus lays the ground work for identifying the cell types in bladder tissues and provides potential clues to understand abnormal bladder functions.

scholarly journals Protocol for CardioCluster Creation

2020 ◽  
Author(s):  
Megan M Monsanto ◽  
Mark A Sussman
Keyword(s):  
Interstitial Cell ◽  
Cellular Therapy ◽  
3D Structure ◽  
Cell Loss ◽  
Cell Types ◽  
Heart Tissue ◽  
Cellular Interaction ◽  
Treat Heart Failure ◽  
Working Together ◽  
Intense Research

Abstract Cellular therapy to treat heart failure is an ongoing focus of intense research, but with limited progress. Engineered augmentation of established cellular effectors overcomes impediments, enhancing reparative activity. Such ‘next generation’ implementation includes delivery of combinatorial cell populations working together synergistically. Concurrent isolation and expansion of three distinct cardiac-derived interstitial cell types from human heart tissue prompted design of a 3D structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell loss. Here we describe a method wherein, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments termed CardioClusters.

scholarly journals Hepatotoxicity and nephrotoxicity following long-term prenatal exposure of paracetamol in the neonatal rat: is betaine protective?

2020 ◽  
Vol 45 (1) ◽  
pp. 99-107
Author(s):  
Mete Özkoç ◽  
Hadi Karimkhani ◽  
Güngör Kanbak ◽  
Dilek Burukoğlu Dönmez
Keyword(s):  
Nitric Oxide ◽  
Tissue Injury ◽  
Physiological Saline ◽  
Neonatal Rat ◽  
Protective Effects ◽  
Analgesic Drug ◽  
Tissue Samples ◽  
The World ◽  
Histological Results

AbstractBackgroundParacetamol is one of the widely used antipyretic and analgesic drug around the world. Many researchers showed that paracetamol caused to hepatotoxicity or nephrotoxicity.ObjectiveIn the present study, we aimed to determine whether betaine has protective effects on hepatotoxicity and nephrotoxicity in neonate rats, following to long term maternal paracetamol exposure.Materials and methodsRandomly chosen neonates, from the neonate pools, were divided into three groups; Control (n=13), APAP (n=13), and APAP+Betaine (n=13). Physiological saline, paracetamol (30 mg/kg/day), and paracetamol (30 mg/kg/day)+betaine (800 mg/kg/day) were orally administered to the relevant groups during the pregnancy period (approximately 21 day). Following to the birth, neonates were decapitated under anaesthesia and tissue samples were taken for biochemical and histological analyses.ResultsThe statistical analysis showed that, malondialdehyde and nitric oxide levels increase significantly in APAP group, while paraoxonase, arylesterase activity and glutathione levels decrease. After the betaine administration, glutathione levels, paraoxonase and arylesterase activities increased while malondialdehyde and nitric oxide levels decreased in APAP+betaine group. These biochemical findings also were supported by histological results.ConclusionIn this study, our biochemical and histological findings indicate that betaine can protect the tissue injury caused by paracetamol.

scholarly journals Marker Expression of Interstitial Cells in Human Skeletal Muscle: An Immunohistochemical Study

2019 ◽  
Vol 67 (11) ◽  
pp. 825-844
Author(s):  
Eva K. Hejbøl ◽  
Mohammad A. Hajjaj ◽  
Ole Nielsen ◽  
Henrik D. Schrøder
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Growth Factor ◽  
Human Skeletal Muscle ◽  
Interstitial Cell ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Interstitial Cells ◽  
Platelet Derived Growth Factor ◽  
Myogenic Stem Cells

There is a growing recognition that myogenic stem cells are influenced by their microenvironment during regeneration. Several interstitial cell types have been described as supportive for myoblasts. In this role, both the pericyte as a possible progenitor for mesenchymal stem cells, and interstitial cells in the endomysium have been discussed. We have applied immunohistochemistry on normal and pathological human skeletal muscle using markers for pericytes, or progenitor cells and found a cell type co-expressing CD10, CD34, CD271, and platelet-derived growth factor receptor α omnipresent in the endomysium. The marker profile of these cells changed dynamically in response to muscle damage and atrophy, and they proliferated in response to damage. The cytology and expression profile of the CD10+ cells indicated a capacity to participate in myogenesis. Both morphology and indicated function of these cells matched properties of several previously described interstitial cell types. Our study suggests a limited number of cell types that could embrace many of these described cell types. Our study indicate that the CD10+, CD34+, CD271+, and platelet-derived growth factor receptor α+ cells could have a supportive role in human muscle regeneration, and thus the mechanisms by which they exert their influence could be implemented in stem cell therapy.

scholarly journals Effects of Cardiotoxins on Cardiac Stem and Progenitor Cell Populations

2021 ◽  
Vol 8 ◽  
Author(s):  
Andrew J. Smith
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Kinase Inhibitors ◽  
Full Range ◽  
Cell Types ◽  
Myocardial Cell ◽  
Cell Populations ◽  
Negative Effects ◽  
Myocardial Repair

As research and understanding of the cardiotoxic side-effects of anticancer therapy expands further and the affected patient population grows, notably the long-term survivors of childhood cancers, it is important to consider the full range of myocardial cell types affected. While the direct impacts of these toxins on cardiac myocytes constitute the most immediate damage, over the longer term, the myocardial ability to repair, or adapt to this damage becomes an ever greater component of the disease phenotype. One aspect is the potential for endogenous myocardial repair and renewal and how this may be limited by cardiotoxins depleting the cells that contribute to these processes. Clear evidence exists of new cardiomyocyte formation in adult human myocardium, along with the identification in the myocardium of endogenous stem/progenitor cell populations with pro-regenerative properties. Any effects of cardiotoxins on either of these processes will worsen long-term prognosis. While the role of cardiac stem/progenitor cells in cardiomyocyte renewal appears at best limited (although with stronger evidence of this process in response to diffuse cardiomyocyte loss), there are strong indications of a pro-regenerative function through the support of injured cell survival. A number of recent studies have identified detrimental impacts of anticancer therapies on cardiac stem/progenitor cells, with negative effects seen from both long-established chemotherapy agents such as, doxorubicin and from newer, less overtly cardiotoxic agents such as tyrosine kinase inhibitors. Damaging impacts are seen both directly, on cell numbers and viability, but also on these cells' ability to maintain the myocardium through generation of pro-survival secretome and differentiated cells. We here present a review of the identified impacts of cardiotoxins on cardiac stem and progenitor cells, considered in the context of the likely role played by these cells in the maintenance of myocardial tissue homeostasis.

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