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Pushp P, Nogueira DES, Rodrigues CAV, Ferreira FC, Cabral JMS, Gupta MK. A Concise Review on Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Personalized Regenerative Medicine. Stem Cell Rev Rep 2021; 17:748-776. [PMID: 33098306 DOI: 10.1007/s12015-020-10061-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2020] [Indexed: 02/07/2023]
Abstract
The induced pluripotent stem cells (iPSCs) are derived from somatic cells by using reprogramming factors such as Oct4, Sox2, Klf4, and c-Myc (OSKM) or Oct4, Sox2, Nanog and Lin28 (OSNL). They resemble embryonic stem cells (ESCs) and have the ability to differentiate into cell lineage of all three germ-layer, including cardiomyocytes (CMs). The CMs can be generated from iPSCs by inducing embryoid bodies (EBs) formation and treatment with activin A, bone morphogenic protein 4 (BMP4), and inhibitors of Wnt signaling. However, these iPSC-derived CMs are a heterogeneous population of cells and require purification and maturation to mimic the in vivo CMs. The matured CMs can be used for various therapeutic purposes in regenerative medicine by cardiomyoplasty or through the development of tissue-engineered cardiac patches. In recent years, significant advancements have been made in the isolation of iPSC and their differentiation, purification, and maturation into clinically usable CMs. Newer small molecules have also been identified to substitute the reprogramming factors for iPSC generation as well as for direct differentiation of somatic cells into CMs without an intermediary pluripotent state. This review provides a concise update on the generation of iPSC-derived CMs and their application in personalized cardiac regenerative medicine. It also discusses the current limitations and challenges in the application of iPSC-derived CMs. Graphical abstract.
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Affiliation(s)
- Pallavi Pushp
- Department of Biotechnology, Institute of Engineering and Technology (IET), Bundelkhand University, Jhansi, Uttar Pradesh, 284128, India
- Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha, 769 008, India
| | - Diogo E S Nogueira
- Department of Bioengineering, and iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
| | - Carlos A V Rodrigues
- Department of Bioengineering, and iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
| | - Frederico C Ferreira
- Department of Bioengineering, and iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
| | - Joaquim M S Cabral
- Department of Bioengineering, and iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
| | - Mukesh Kumar Gupta
- Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha, 769 008, India.
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Li Calzi S, Cook T, Della Rocca DG, Zhang J, Shenoy V, Yan Y, Espejo A, Rathinasabapathy A, Jacobsen MH, Salazar T, Sandusky GE, Shaw LC, March K, Raizada MK, Pepine CJ, Katovich MJ, Grant MB. Complementary Embryonic and Adult Cell Populations Enhance Myocardial Repair in Rat Myocardial Injury Model. Stem Cells Int 2019; 2019:3945850. [PMID: 31781239 PMCID: PMC6875168 DOI: 10.1155/2019/3945850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 04/09/2019] [Accepted: 10/01/2019] [Indexed: 11/18/2022] Open
Abstract
We compared the functional outcome of Isl-1+ cardiac progenitors, CD90+ bone marrow-derived progenitor cells, and the combination of the two in a rat myocardial infarction (MI) model. Isl-1+ cells were isolated from embryonic day 12.5 (E12.5) rat hearts and expanded in vitro. Thy-1+/CD90+ cells were isolated from the bone marrow of adult Sprague-Dawley rats by immunomagnetic cell sorting. Six-week-old female Sprague-Dawley rats underwent permanent left anterior descending (LAD) coronary artery ligation and received intramyocardial injection of either saline, Isl-1+ cells, CD90+ cells, or a combination of Isl-1+ and CD90+ cells, at the time of infarction. Cells were delivered transepicardially to the peri-infarct zone. Left ventricular function was assessed by transthoracic echocardiography at 1- and 4-week post-MI and by Millar catheterization (-dP/dt and +dP/dt) at 4-week post-MI. Fluorescence in situ hybridization (Isl-1+cells) and monochrystalline iron oxide nanoparticles labeling (MION; CD90+ cells) were performed to assess biodistribution of transplanted cells. Only the combination of cells demonstrated a significant improvement of cardiac function as assessed by anterior wall contractility, dP/dt (max), and dP/dt (min), compared to Isl-1+ or CD90+ cell monotherapies. In the combination cell group, viable cells were detected at week 4 when anterior wall motion was completely restored. In conclusion, the combination of Isl-1+ cardiac progenitors and adult bone marrow-derived CD90+ cells shows prolonged and robust myocardial tissue repair and provides support for the use of complementary cell populations to enhance myocardial repair.
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Affiliation(s)
- Sergio Li Calzi
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-0001, USA
| | - Todd Cook
- Department of Medicine, IUPUI, Indianapolis, IN 46202, USA
| | | | - Juan Zhang
- Department of Pharmacodynamics, University of Florida, Gainesville, FL 32611, USA
| | - Vinayak Shenoy
- Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32611, USA
| | - Yuanqing Yan
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Andrew Espejo
- Department of Pharmacodynamics, University of Florida, Gainesville, FL 32611, USA
| | | | - Max H. Jacobsen
- Pathology and Laboratory Med., IUPUI, Indianapolis, IN 46202, USA
| | - Tatiana Salazar
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-0001, USA
| | | | - Lynn C. Shaw
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-0001, USA
| | - Keith March
- Department of Medicine, IUPUI, Indianapolis, IN 46202, USA
| | - Mohan K. Raizada
- Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32611, USA
| | - Carl J. Pepine
- Department of Medicine, University of Florida, Gainesville, FL 32611, USA
| | - Michael J. Katovich
- Department of Pharmacodynamics, University of Florida, Gainesville, FL 32611, USA
| | - Maria B. Grant
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-0001, USA
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Sullivan KE, Burns LJ, Black LD. An in vitro model for the assessment of stem cell fate following implantation within the infarct microenvironment identifies ISL-1 expression as the strongest predictor of c-Kit(+) cardiac progenitor cells' therapeutic potential. J Mol Cell Cardiol 2015; 88:91-100. [PMID: 26393440 DOI: 10.1016/j.yjmcc.2015.09.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 09/15/2015] [Accepted: 09/15/2015] [Indexed: 02/01/2023]
Abstract
Cell therapy has the potential to drastically improve clinical outcomes for the 1.45 million patients suffering from a myocardial infarction (MI) each year in the U.S. However, the limitations associated with this treatment - including poor engraftment, significant cell death and poor differentiation potential - have prevented its widespread application clinically. To optimize functional improvements provided by transplanted cells, there is a need to develop methods that increase cellular retention and viability, while supporting differentiation and promoting paracrine signaling. Current in vivo models are expensive, difficult to access and manipulate and are time consuming. We have developed an in vitro model of MI which allows for a straightforward, consistent and relatively accurate prediction of cell fate following injection in vivo. The model demonstrated how the infarct environment impairs cellular engraftment and differentiation, but identified an implantation strategy which enhanced cell fate in vitro. Multivariate linear regression identified variables within the model that regulated vascular differentiation potential including oxygen tension, stiffness and cytokine presence, while cardiac differentiation was more accurately predicted by Isl-1 expression in the original cell isolate than any other variable present within the model system. The model highlighted how the cells' sensitivity to the infarct variables varied from line to line, which emphasizes the importance of the model system for the prediction of cell fate on a patient specific basis. Further development of this model system could help predict the clinical efficacy of cardiac progenitor cell therapy at the patient level as well as identify the optimal strategy for cell delivery.
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Affiliation(s)
- Kelly E Sullivan
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Laura J Burns
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
| | - Lauren D Black
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA; Cellular, Molecular, and Developmental Biology Program, Sackler School for Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
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Milasinovic D, Mohl W. Contemporary perspective on endogenous myocardial regeneration. World J Stem Cells 2015; 7:793-805. [PMID: 26131310 PMCID: PMC4478626 DOI: 10.4252/wjsc.v7.i5.793] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Revised: 03/01/2015] [Accepted: 04/20/2015] [Indexed: 02/06/2023] Open
Abstract
Considering the complex nature of the adult heart, it is no wonder that innate regenerative processes, while maintaining adequate cardiac function, fall short in myocardial jeopardy. In spite of these enchaining limitations, cardiac rejuvenation occurs as well as restricted regeneration. In this review, the background as well as potential mechanisms of endogenous myocardial regeneration are summarized. We present and analyze the available evidence in three subsequent steps. First, we examine the experimental research data that provide insights into the mechanisms and origins of the replicating cardiac myocytes, including cell populations referred to as cardiac progenitor cells (i.e., c-kit+ cells). Second, we describe the role of clinical settings such as acute or chronic myocardial ischemia, as initiators of pathways of endogenous myocardial regeneration. Third, the hitherto conducted clinical studies that examined different approaches of initiating endogenous myocardial regeneration in failing human hearts are analyzed. In conclusion, we present the evidence in support of the notion that regaining cardiac function beyond cellular replacement of dysfunctional myocardium via initiation of innate regenerative pathways could create a new perspective and a paradigm change in heart failure therapeutics. Reinitiating cardiac morphogenesis by reintroducing developmental pathways in the adult failing heart might provide a feasible way of tissue regeneration. Based on our hypothesis “embryonic recall”, we present first supporting evidence on regenerative impulses in the myocardium, as induced by developmental processes.
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Ge Z, Lal S, Le TYL, Dos Remedios C, Chong JJH. Cardiac stem cells: translation to human studies. Biophys Rev 2014; 7:127-139. [PMID: 28509972 DOI: 10.1007/s12551-014-0148-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Accepted: 11/13/2014] [Indexed: 02/08/2023] Open
Abstract
The discovery of multiple classes of cardiac progenitor cells in the adult mammalian heart has generated hope for their use as a therapeutic in heart failure. However, successful results from animal models have not always yielded similar findings in human studies. Recent Phase I/II trials of c-Kit (SCIPIO) and cardiosphere-based (CADUCEUS) cardiac progenitor cells have demonstrated safety and some therapeutic efficacy. Gaps remain in our understanding of the origins, function and relationships between the different progenitor cell families, many of which are heterogeneous populations with overlapping definitions. Another challenge lies in the limitations of small animal models in replicating the human heart. Cryopreserved human cardiac tissue provides a readily available source of cardiac progenitor cells and may help address these questions. We review important findings and relative unknowns of the main classes of cardiac progenitor cells, highlighting differences between animal and human studies.
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Affiliation(s)
- Zijun Ge
- Bosch Institute, The University of Sydney, Sydney, Australia.,Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Sean Lal
- Bosch Institute, The University of Sydney, Sydney, Australia.,Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Thi Y L Le
- Department of Cardiology Westmead Hospital, Sydney, NSW, Australia.,Centre for Heart Research, Westmead Millennium Institute for Medical Research, 176 Hawkesbury Road, Westmead, Sydney, NSW, Australia, 2145
| | | | - James J H Chong
- Department of Cardiology Westmead Hospital, Sydney, NSW, Australia. .,Sydney Medical School, University of Sydney, Sydney, NSW, Australia. .,Centre for Heart Research, Westmead Millennium Institute for Medical Research, 176 Hawkesbury Road, Westmead, Sydney, NSW, Australia, 2145.
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6
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Marino Gammazza A, Rizzo M, Citarrella R, Rappa F, Campanella C, Bucchieri F, Patti A, Nikolic D, Cabibi D, Amico G, Conaldi PG, San Biagio PL, Montalto G, Farina F, Zummo G, Conway de Macario E, Macario AJL, Cappello F. Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis. Cell Stress Chaperones 2014; 19:343-53. [PMID: 24057177 PMCID: PMC3982029 DOI: 10.1007/s12192-013-0460-9] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Revised: 09/02/2013] [Accepted: 09/03/2013] [Indexed: 01/10/2023] Open
Abstract
The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto's thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on fine needle aspiration cytology. By bioinformatics, we found regions in the Hsp60 molecule with remarkable structural similarity with the thyroglobulin (TG) and thyroid peroxidase (TPO) molecules, which supports the notion that autoantibodies against TG and TPO are likely to recognize Hsp60 on the plasma membrane of oncocytes. This was also supported by data obtained by ELISA, showing that anti-TG and anti-TPO antibodies cross-react with human recombinant Hsp60. Antibody-antigen (Hsp60) reaction on the cell surface could very well mediate thyroid cell damage and destruction, perpetuating inflammation. Experiments with recombinant Hsp60 did not show stimulation of cytokine production by peripheral blood mononuclear cells from HT patients. All together, these results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism.
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Affiliation(s)
- Antonella Marino Gammazza
- />Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
- />Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
| | - Manfredi Rizzo
- />Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
- />Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Roberto Citarrella
- />Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Francesca Rappa
- />Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
- />Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
| | - Claudia Campanella
- />Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
- />Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
| | - Fabio Bucchieri
- />Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
- />Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
| | - Angelo Patti
- />Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
- />Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Dragana Nikolic
- />Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
- />Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Daniela Cabibi
- />Department of Human Pathology, University of Palermo, Palermo, Italy
| | - Giandomenico Amico
- />Istituto Mediterraneo per i Trapianti e Terapie (ISMETT) ad Alta Specializzazione and RIMED Foundation, Palermo, Italy
| | - Pier Giulio Conaldi
- />Istituto Mediterraneo per i Trapianti e Terapie (ISMETT) ad Alta Specializzazione and RIMED Foundation, Palermo, Italy
| | - Pier Luigi San Biagio
- />Institute of Biophysics (IBF), National Research Council of Italy (CNR), Palermo, Italy
| | - Giuseppe Montalto
- />Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Felicia Farina
- />Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
| | - Giovanni Zummo
- />Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
| | - Everly Conway de Macario
- />Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, and IMET, Columbus Center, Baltimore, MD USA
| | - Alberto J. L. Macario
- />Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
- />Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, and IMET, Columbus Center, Baltimore, MD USA
| | - Francesco Cappello
- />Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
- />Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
- />Institute of Biophysics (IBF), National Research Council of Italy (CNR), Palermo, Italy
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Abstract
Myocardial infarction leads to loss of cardiomyocytes, scar formation, ventricular remodeling and eventually deterioration of heart function. Over the past decade, stem cell therapy has emerged as a novel strategy for patients with ischemic heart disease and its beneficial effects have been demonstrated by substantial preclinical and clinical studies. Efficacy of several types of stem cells in the therapy of cardiovascular diseases has already been evaluated. However, repair of injured myocardium through stem cell transplantation is restricted by critical safety issues and ethic concerns. Recently, the discovery of cardiac stem cells (CSCs) that reside in the heart itself brings new prospects for myocardial regeneration and reconstitution of cardiac tissues. CSCs are positive for various stem cell markers and have the potential of self-renewal and multilineage differentiation. They play a pivotal role in the maintenance of heart homeostasis and cardiac repair. Elucidation of their biological characteristics and functions they exert in myocardial infarction are very crucial to further investigations on them. This review will focus on the field of cardiac stem cells and discuss technical and practical issues that may involve in their clinical applications in myocardial infarction.
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Pellicciari C. Histochemistry as an irreplaceable approach for investigating functional cytology and histology. Eur J Histochem 2013; 57:e41. [PMID: 24441194 PMCID: PMC3896043 DOI: 10.4081/ejh.2013.e41] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Accepted: 12/17/2013] [Indexed: 12/19/2022] Open
Abstract
In agreement with the evolution of histochemistry over the last fifty years and thanks to the impressive advancements in microscopy sciences, the application of cytochemical techniques to light and electron microscopy is more and more addressed to elucidate the functional characteristics of cells and tissue under different physiological, pathological or experimental conditions. Simultaneously, the mere description of composition and morphological features has become increasingly sporadic in the histochemical literature. Since basic research on cell functional organization is essential for understanding the mechanisms responsible for major biological processes such as differentiation or growth control in normal and tumor tissues, histochemical Journals will continue to play a pivotal role in the field of cell and tissue biology in all its structural and functional aspects.
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Barone R, Macaluso F, Catanese P, Marino Gammazza A, Rizzuto L, Marozzi P, Lo Giudice G, Stampone T, Cappello F, Morici G, Zummo G, Farina F, Di Felice V. Endurance exercise and conjugated linoleic acid (CLA) supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis. PLoS One 2013; 8:e79686. [PMID: 24223995 PMCID: PMC3818175 DOI: 10.1371/journal.pone.0079686] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Accepted: 09/24/2013] [Indexed: 01/12/2023] Open
Abstract
A new role for fat supplements, in particular conjugated linoleic acid (CLA), has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C) supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone and an up-regulation of CYP17A1 mRNA and protein. The effect of training on CYP17A1 expression and testosterone biosynthesis was significantly higher in the trained mice supplemented with CLA compared to the placebo. The results of the present study demonstrated that CLA stimulates testosterone biosynthesis via CYP17A1, and endurance training led to the synthesis of testosterone in vivo by inducing the overexpression of CYP17A1 mRNA and protein in the Leydig cells of the testis. This effect was enhanced by CLA supplementation. Therefore, CLA-associated physical activity may be used for its steroidogenic property in different fields, such as alimentary industry, human reproductive medicine, sport science, and anti-muscle wasting.
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Affiliation(s)
- Rosario Barone
- Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), University of Palermo, Palermo, Italy
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10
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Fuentes TI, Appleby N, Tsay E, Martinez JJ, Bailey L, Hasaniya N, Kearns-Jonker M. Human neonatal cardiovascular progenitors: unlocking the secret to regenerative ability. PLoS One 2013; 8:e77464. [PMID: 24204836 PMCID: PMC3810469 DOI: 10.1371/journal.pone.0077464] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2013] [Accepted: 09/03/2013] [Indexed: 01/07/2023] Open
Abstract
Although clinical benefit can be achieved after cardiac transplantation of adult c-kit+ or cardiosphere-derived cells for myocardial repair, these stem cells lack the regenerative capacity unique to neonatal cardiovascular stem cells. Unraveling the molecular basis for this age-related discrepancy in function could potentially transform cardiovascular stem cell transplantation. In this report, clonal populations of human neonatal and adult cardiovascular progenitor cells were isolated and characterized, revealing the existence of a novel subpopulation of endogenous cardiovascular stem cells that persist throughout life and co-express both c-kit and isl1. Epigenetic profiling identified 41 microRNAs whose expression was significantly altered with age in phenotypically-matched clones. These differences were correlated with reduced proliferation and a limited capacity to invade in response to growth factor stimulation, despite high levels of growth factor receptor on progenitors isolated from adults. Further understanding of these differences may provide novel therapeutic targets to enhance cardiovascular regenerative capacity.
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Affiliation(s)
- Tania I. Fuentes
- Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America
| | - Nancy Appleby
- Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America
| | - Eric Tsay
- Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America
| | - J. Julian Martinez
- Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America
| | - Leonard Bailey
- Department of Cardiothoracic Surgery, Loma Linda University School of Medicine, Loma Linda, California, United States of America
| | - Nahidh Hasaniya
- Department of Cardiothoracic Surgery, Loma Linda University School of Medicine, Loma Linda, California, United States of America
| | - Mary Kearns-Jonker
- Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, United States of America
- * E-mail:
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11
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Di Felice V, Zummo G. Stem cell populations in the heart and the role of Isl1 positive cells. Eur J Histochem 2013; 57:e14. [PMID: 23807293 PMCID: PMC3794340 DOI: 10.4081/ejh.2013.e14] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2012] [Revised: 02/04/2013] [Accepted: 02/08/2013] [Indexed: 11/23/2022] Open
Abstract
Cardiac progenitor cells are multipotent stem cells isolated from both embryonic and adult hearts in several species and are able to differentiate at least into smooth muscle cells, endothelial cells and cardiomyocytes. The embryonic origin of these cells has not yet been demonstrated, but it has been suggested that these cells may derive from the first and secondary heart fields and from the neural crest. In the last decade, two diffe-rent populations of cardiac progenitor or stem cells have been identified and isolated, i.e., the Islet1 positive (Isl1+) and c-Kit positive (c-Kit+)/Stem Cell Antigen-1 positive (Sca-1+) cells. Until 2012, these two populations have been considered two separate entities with different roles and a different origin, but new evidence now suggests a con-nection between the two populations and that the two populations may represent two subpopulations of a unique pool of cardiac stem cells, derived from a common immature primitive cell. To find a common consensus on this concept is very important in furthe-ring the application of stem cells to cardiac tissue engineering.
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Affiliation(s)
- V Di Felice
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, 90127 Palermo, Italy.
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12
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Di Felice V, Serradifalco C, Rizzuto L, De Luca A, Rappa F, Barone R, Di Marco P, Cassata G, Puleio R, Verin L, Motta A, Migliaresi C, Guercio A, Zummo G. Silk fibroin scaffolds enhance cell commitment of adult rat cardiac progenitor cells. J Tissue Eng Regen Med 2013; 9:E51-64. [PMID: 23592297 DOI: 10.1002/term.1739] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2012] [Revised: 01/18/2013] [Accepted: 02/05/2013] [Indexed: 01/30/2023]
Abstract
The use of three-dimensional (3D) cultures may induce cardiac progenitor cells to synthesize their own extracellular matrix (ECM) and sarcomeric proteins to initiate cardiac differentiation. 3D cultures grown on synthetic scaffolds may favour the implantation and survival of stem cells for cell therapy when pharmacological therapies are not efficient in curing cardiovascular diseases and when organ transplantation remains the only treatment able to rescue the patient's life. Silk fibroin-based scaffolds may be used to increase cell affinity to biomaterials and may be chemically modified to improve cell adhesion. In the present study, porous, partially orientated and electrospun nanometric nets were used. Cardiac progenitor cells isolated from adult rats were seeded by capillarity in the 3D structures and cultured inside inserts for 21 days. Under this condition, the cells expressed a high level of sarcomeric and cardiac proteins and synthesized a great quantity of ECM. In particular, partially orientated scaffolds induced the synthesis of titin, which is a fundamental protein in sarcomere assembly.
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Affiliation(s)
- Valentina Di Felice
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy
| | - Claudia Serradifalco
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy
| | - Luigi Rizzuto
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy
| | - Angela De Luca
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy
| | - Francesca Rappa
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy
| | - Rosario Barone
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy
| | | | - Giovanni Cassata
- Istituto Zooprofilattico Sperimentale della Sicilia, Palermo, Italy
| | - Roberto Puleio
- Istituto Zooprofilattico Sperimentale della Sicilia, Palermo, Italy
| | - Lucia Verin
- Department of Materials Engineering and Industrial Technologies and Biotech Research Centre, University of Trento, Italy
- European Institute of Excellence in Tissue Engineering and Regenerative Medicine and INSTM Research Unit, Trento, Italy
| | - Antonella Motta
- Department of Materials Engineering and Industrial Technologies and Biotech Research Centre, University of Trento, Italy
- European Institute of Excellence in Tissue Engineering and Regenerative Medicine and INSTM Research Unit, Trento, Italy
| | - Claudio Migliaresi
- Department of Materials Engineering and Industrial Technologies and Biotech Research Centre, University of Trento, Italy
- European Institute of Excellence in Tissue Engineering and Regenerative Medicine and INSTM Research Unit, Trento, Italy
| | - Annalisa Guercio
- Istituto Zooprofilattico Sperimentale della Sicilia, Palermo, Italy
| | - Giovanni Zummo
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy
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Abstract
Stem cell-based therapies hold promise for regenerating the myocardium after injury. Recent data obtained from phase I clinical trials using endogenous cardiovascular progenitors isolated directly from the heart suggest that cell-based treatment for heart patients using stem cells that reside in the heart provides significant functional benefit and an improvement in patient outcome. Methods to achieve improved engraftment and regeneration may extend this therapeutic benefit. Endogenous cardiovascular progenitors have been tested extensively in small animals to identify cells that improve cardiac function after myocardial infarction. However, the relative lack of large animal models impedes translation into clinical practice. This review will exclusively focus on the latest research pertaining to humans and large animals, including both endogenous and induced sources of cardiovascular progenitors.
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Affiliation(s)
- Tania Fuentes
- Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA
| | - Mary Kearns-Jonker
- Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA
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Macaluso F, Barone R, Catanese P, Carini F, Rizzuto L, Farina F, Di Felice V. Do fat supplements increase physical performance? Nutrients 2013; 5:509-24. [PMID: 23434906 PMCID: PMC3635209 DOI: 10.3390/nu5020509] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Revised: 01/07/2013] [Accepted: 01/31/2013] [Indexed: 01/07/2023] Open
Abstract
Fish oil and conjugated linoleic acid (CLA) belong to a popular class of food supplements known as "fat supplements", which are claimed to reduce muscle glycogen breakdown, reduce body mass, as well as reduce muscle damage and inflammatory responses. Sport athletes consume fish oil and CLA mainly to increase lean body mass and reduce body fat. Recent evidence indicates that this kind of supplementation may have other side-effects and a new role has been identified in steroidogenensis. Preliminary findings demonstrate that fish oil and CLA may induce a physiological increase in testosterone synthesis. The aim of this review is to describe the effects of fish oil and CLA on physical performance (endurance and resistance exercise), and highlight the new results on the effects on testosterone biosynthesis. In view of these new data, we can hypothesize that fat supplements may improve the anabolic effect of exercise.
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Affiliation(s)
- Filippo Macaluso
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy.
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Pellicciari C. On the future contents of a small journal of histochemistry. Eur J Histochem 2012; 56:e51. [PMID: 23361247 PMCID: PMC3567770 DOI: 10.4081/ejh.2012.e51] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 12/04/2012] [Indexed: 02/07/2023] Open
Abstract
In the last three years, more than 70,000 scientific articles have been published in peer reviewed journals on the application of histochemistry in the biomedical field: most of them did not appear in strictly histochemical journals, but in others dealing with cell and molecular biology, medicine or biotechnology. This proves that histochemistry is still an active and innovative discipline with relevance in basic and applied biological research, but also demonstrates that especially the small histochemical journals should likely reconsider their scopes and strategies to preserve their authorship. A review of the last three years volumes of the European Journal of Histochemistry, taken as an example of a long-time established small journal, confirmed that the published articles were widely heterogeneous in their topics and experimental models, as in this journal's tradition. This strongly suggests that a journal of histochemistry should keep its role as a forum open to an audience as broad as possible, publishing papers on cell and tissue biology in a wide variety of models. This will improve knowledge of the basic mechanisms of development and differentiation, while helping to increase the number of potential authors since scientists who generally do not use histochemistry in their research will find hints for the applications of histochemical techniques to novel still unexplored subjects.
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Affiliation(s)
- C Pellicciari
- Dipartimento di Biologia e Biotecnologie “Lazzaro Spallanzani”,University of Pavia, Italy.
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