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Park YS, Park BW, Choi H, Lee SH, Kim M, Park HJ, Kim IB. Chorion-derived perinatal mesenchymal stem cells improve cardiac function and vascular regeneration: preferential treatment for ischemic heart disease. Hellenic J Cardiol 2022; 66:52-58. [DOI: 10.1016/j.hjc.2022.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 05/24/2022] [Accepted: 05/24/2022] [Indexed: 11/04/2022] Open
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Tang XL, Wysoczynski M, Gumpert AM, Li Y, Wu WJ, Li H, Stowers H, Bolli R. Effect of intravenous cell therapy in rats with old myocardial infarction. Mol Cell Biochem 2022; 477:431-444. [PMID: 34783963 PMCID: PMC8896398 DOI: 10.1007/s11010-021-04283-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 10/21/2021] [Indexed: 10/19/2022]
Abstract
Mounting evidence shows that cell therapy provides therapeutic benefits in experimental and clinical settings of chronic heart failure. However, direct cardiac delivery of cells via transendocardial injection is logistically complex, expensive, entails risks, and is not amenable to multiple dosing. Intravenous administration would be a more convenient and clinically applicable route for cell therapy. Thus, we determined whether intravenous infusion of three widely used cell types improves left ventricular (LV) function and structure and compared their efficacy. Rats with a 30-day-old myocardial infarction (MI) received intravenous infusion of vehicle (PBS) or 1 of 3 types of cells: bone marrow mesenchymal stromal cells (MSCs), cardiac mesenchymal cells (CMCs), and c-kit-positive cardiac cells (CPCs), at a dose of 12 × 106 cells. Rats were followed for 35 days after treatment to determine LV functional status by serial echocardiography and hemodynamic studies. Blood samples were collected for Hemavet analysis to determine inflammatory cell profile. LV ejection fraction (EF) dropped ≥ 20 points in all hearts at 30 days after MI and deteriorated further at 35-day follow-up in the vehicle-treated group. In contrast, deterioration of EF was halted in rats that received MSCs and attenuated in those that received CMCs or CPCs. None of the 3 types of cells significantly altered scar size, myocardial content of collagen or CD45-positive cells, or Hemavet profile. This study demonstrates that a single intravenous administration of 3 types of cells in rats with chronic ischemic cardiomyopathy is effective in attenuating the progressive deterioration in LV function. The extent of LV functional improvement was greatest with CPCs, intermediate with CMCs, and least with MSCs.
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Affiliation(s)
- Xian-Liang Tang
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA
| | - Marcin Wysoczynski
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA
| | - Anna M Gumpert
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA
| | - Yan Li
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA
| | - Wen-Jian Wu
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA
| | - Hong Li
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA
| | - Heather Stowers
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA
| | - Roberto Bolli
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA.
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Martínez-Falguera D, Iborra-Egea O, Gálvez-Montón C. iPSC Therapy for Myocardial Infarction in Large Animal Models: Land of Hope and Dreams. Biomedicines 2021; 9:1836. [PMID: 34944652 PMCID: PMC8698445 DOI: 10.3390/biomedicines9121836] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/30/2021] [Accepted: 12/01/2021] [Indexed: 02/07/2023] Open
Abstract
Myocardial infarction is the main driver of heart failure due to ischemia and subsequent cell death, and cell-based strategies have emerged as promising therapeutic methods to replace dead tissue in cardiovascular diseases. Research in this field has been dramatically advanced by the development of laboratory-induced pluripotent stem cells (iPSCs) that harbor the capability to become any cell type. Like other experimental strategies, stem cell therapy must meet multiple requirements before reaching the clinical trial phase, and in vivo models are indispensable for ensuring the safety of such novel therapies. Specifically, translational studies in large animal models are necessary to fully evaluate the therapeutic potential of this approach; to empirically determine the optimal combination of cell types, supplementary factors, and delivery methods to maximize efficacy; and to stringently assess safety. In the present review, we summarize the main strategies employed to generate iPSCs and differentiate them into cardiomyocytes in large animal species; the most critical differences between using small versus large animal models for cardiovascular studies; and the strategies that have been pursued regarding implanted cells' stage of differentiation, origin, and technical application.
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Affiliation(s)
- Daina Martínez-Falguera
- Faculty of Medicine, University of Barcelona (UB), 08036 Barcelona, Spain;
- ICREC Research Program, Germans Trias i Pujol Health Research Institute, Can Ruti Campus, 08916 Badalona, Spain;
- Heart Institute (iCor), Germans Trias i Pujol University Hospital, 08916 Badalona, Spain
| | - Oriol Iborra-Egea
- ICREC Research Program, Germans Trias i Pujol Health Research Institute, Can Ruti Campus, 08916 Badalona, Spain;
- Heart Institute (iCor), Germans Trias i Pujol University Hospital, 08916 Badalona, Spain
| | - Carolina Gálvez-Montón
- ICREC Research Program, Germans Trias i Pujol Health Research Institute, Can Ruti Campus, 08916 Badalona, Spain;
- Heart Institute (iCor), Germans Trias i Pujol University Hospital, 08916 Badalona, Spain
- CIBERCV, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Institut d’Investigació Biomèdica de Bellvitge-IDIBELL, L’Hospitalet de Llobregat, 08908 Barcelona, Spain
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Kumar D, Talluri TR, Selokar NL, Hyder I, Kues WA. Perspectives of pluripotent stem cells in livestock. World J Stem Cells 2021; 13:1-29. [PMID: 33584977 PMCID: PMC7859985 DOI: 10.4252/wjsc.v13.i1.1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 09/28/2020] [Accepted: 11/09/2020] [Indexed: 02/06/2023] Open
Abstract
The recent progress in derivation of pluripotent stem cells (PSCs) from farm animals opens new approaches not only for reproduction, genetic engineering, treatment and conservation of these species, but also for screening novel drugs for their efficacy and toxicity, and modelling of human diseases. Initial attempts to derive PSCs from the inner cell mass of blastocyst stages in farm animals were largely unsuccessful as either the cells survived for only a few passages, or lost their cellular potency; indicating that the protocols which allowed the derivation of murine or human embryonic stem (ES) cells were not sufficient to support the maintenance of ES cells from farm animals. This scenario changed by the innovation of induced pluripotency and by the development of the 3 inhibitor culture conditions to support naïve pluripotency in ES cells from livestock species. However, the long-term culture of livestock PSCs while maintaining the full pluripotency is still challenging, and requires further refinements. Here, we review the current achievements in the derivation of PSCs from farm animals, and discuss the potential application areas.
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Affiliation(s)
- Dharmendra Kumar
- Animal Physiology and Reproduction Division, ICAR-Central Institute for Research on Buffaloes, Hisar 125001, India.
| | - Thirumala R Talluri
- Equine Production Campus, ICAR-National Research Centre on Equines, Bikaner 334001, India
| | - Naresh L Selokar
- Animal Physiology and Reproduction Division, ICAR-Central Institute for Research on Buffaloes, Hisar 125001, India
| | - Iqbal Hyder
- Department of Physiology, NTR College of Veterinary Science, Gannavaram 521102, India
| | - Wilfried A Kues
- Department of Biotechnology, Friedrich-Loeffler-Institute, Federal Institute of Animal Health, Neustadt 31535, Germany
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Lara-Martínez LA, Gutiérrez-Villegas I, Arenas-Luna VM, Hernández-Gutierrez S. [Stem cells: searching predisposition to cardiac commitment by surface markers expression]. ARCHIVOS DE CARDIOLOGIA DE MEXICO 2018; 88:483-495. [PMID: 29311024 DOI: 10.1016/j.acmx.2017.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 11/30/2017] [Accepted: 12/01/2017] [Indexed: 11/19/2022] Open
Abstract
It is well-known that cardiovascular diseases are the leading cause of death worldwide, and represent an important economic burden to health systems. In an attempt to solve this problem, stem cell therapy has emerged as a therapeutic option. Within the last 20 years, a great variety of stem cells have been used in different myocardial infarction models. Up until now, the use of cardiac stem cells (CSCs) has seemed to be the best option, but the inaccessibility and scarcity of these cells make their use unreliable. Additionally, there is a high risk as they have to be obtained directly from the heart of the patient. Unlike CSCs, adult stem cells originating from bone marrow or adipose tissue, among others, appear to be an attractive option due to their easier accessibility and abundance, but particularly due to the probable existence of cardiac progenitors among their different sub-populations. In this review an analysis is made of the surface markers present in CSCs compared with other adult stem cells. This suggested the pre-existence of cells sharing specific surface markers with CSCs, a predictable immunophenotype present in some cells, although in low proportions, and with a potential of cardiac differentiation that could be similar to CSCs, thus increasing their therapeutic value. This study highlights new perspectives regarding MSCs that would enable some of these sub-populations to be differentiated at cardiac tissue level.
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Affiliation(s)
- Luis A Lara-Martínez
- Laboratorio de Biología Molecular, Escuela de Medicina, Universidad Panamericana, Ciudad de México, México
| | - Ingrid Gutiérrez-Villegas
- Laboratorio de Biología Molecular, Escuela de Medicina, Universidad Panamericana, Ciudad de México, México
| | - Victor M Arenas-Luna
- Laboratorio de Biología Molecular, Escuela de Medicina, Universidad Panamericana, Ciudad de México, México
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de Morais SDBV, da Silva LEV, Lataro RM, Silva CAA, de Oliveira LFL, de Carvalho EEV, Simões MV, da Silva Meirelles L, Fazan R, Salgado HC. Mesenchymal Stem Cells Improve Heart Rate Variability and Baroreflex Sensitivity in Rats with Chronic Heart Failure. Stem Cells Dev 2015; 24:2181-92. [PMID: 26059001 DOI: 10.1089/scd.2014.0573] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Heart failure induced by myocardial infarct (MI) attenuates the heart rate variability (HRV) and baroreflex sensitivity, which are important risk factors for life-threatening cardiovascular events. Therapies with mesenchymal stem cells (MSCs) have shown promising results after MI. However, the effects of MSCs on hemodynamic (heart rate and arterial pressure) variability and baroreflex sensitivity in chronic heart failure (CHF) following MI have not been evaluated thus far. Male Wistar rats received MSCs or saline solution intravenously 1 week after ligation of the left coronary artery. Control (noninfarcted) rats were also evaluated. MI size was assessed using single-photon emission computed tomography (SPECT). The left ventricular ejection fraction (LVEF) was evaluated using radionuclide ventriculography. Four weeks after MSC injection, the animals were anesthetized and instrumented for chronic ECG recording and catheters were implanted in the femoral artery to record arterial pressure. Arterial pressure and HRVs were determined in time and frequency domain (spectral analysis) while HRV was also examined using nonlinear methods: DFA (detrended fluctuation analysis) and sample entropy. The initial MI size was the same among all infarcted rats but was reduced by MSCs. CHF rats exhibited increased myocardial interstitial collagen and sample entropy combined with the attenuation of the following cardiocirculatory parameters: DFA indices, LVEF, baroreflex sensitivity, and HRV. Nevertheless, MSCs hampered all these alterations, except the LVEF reduction. Therefore, 4 weeks after MSC therapy was applied to CHF rats, MI size and myocardial interstitial fibrosis decreased, while baroreflex sensitivity and HRV improved.
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Affiliation(s)
| | | | - Renata Maria Lataro
- 1 Department of Physiology, Medical School of Ribeirao Preto, University of Sao Paulo , Ribeirão Preto, Brazil
| | - Carlos Alberto Aguiar Silva
- 1 Department of Physiology, Medical School of Ribeirao Preto, University of Sao Paulo , Ribeirão Preto, Brazil
| | | | | | - Marcus Vinicius Simões
- 2 Department of Internal Medicine, Medical School of Ribeirao Preto, University of Sao Paulo , Ribeirão Preto, Brazil
| | - Lindolfo da Silva Meirelles
- 3 Graduate Program in Cellular and Molecular Biology Applied to Health, Lutheran University of Brazil , Ribeirão Preto, Brazil
| | - Rubens Fazan
- 1 Department of Physiology, Medical School of Ribeirao Preto, University of Sao Paulo , Ribeirão Preto, Brazil
| | - Helio Cesar Salgado
- 1 Department of Physiology, Medical School of Ribeirao Preto, University of Sao Paulo , Ribeirão Preto, Brazil
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Konstantinou D, Lei M, Xia Z, Kanamarlapudi V. Growth factors mediated differentiation of mesenchymal stem cells to cardiac polymicrotissue using hanging drop and bioreactor. Cell Biol Int 2015; 39:502-7. [PMID: 25492631 DOI: 10.1002/cbin.10409] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2014] [Accepted: 10/30/2014] [Indexed: 11/09/2022]
Abstract
Heart disease is the major leading cause of death worldwide and the use of stem cells promises new ways for its treatment. The relatively easy and quick acquisition of human umbilical cord matrix mesenchymal stem cells (HUMSCs) and their properties make them useful for the treatment of cardiac diseases. Therefore, the main aim of this investigation was to create cardiac polymicrotissue from HUMSCs using a combination of growth factors [sphingosine-1-phosphate (S1P) and suramin] and techniques (hanging drop and bioreactor). Using designated culture conditions of the growth factors (100 nM S1P and 500 µM suramin), cardiomyocyte differentiation medium (CDM), hanging drop, bioreactor and differentiation for 7 days, a potential specific cardiac polymicrotissue was derived from HUMSCs. The effectiveness of growth factors alone or in combination in differentiation of HUMSCs to cardiac polymicrotissue was analysed by assessing the presence of cardiac markers by immunocytochemistry. This analysis demonstrated the importance of those growth factors for the differentiation. This study for the first time demonstrated the formation of a cardiac polymicrotissue under specific culture conditions. The polymicrotissue thus obtained may be used in future as a 'patch' to cover the injured cardiac region and would thereby be useful for the treatment of heart diseases.
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Affiliation(s)
- Dimitrios Konstantinou
- School of Biomedicine, University of Manchester, Manchester, UK; Institute of Life Science, College of Medicine, Swansea University, Swansea, UK
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Goichberg P, Chang J, Liao R, Leri A. Cardiac stem cells: biology and clinical applications. Antioxid Redox Signal 2014; 21:2002-17. [PMID: 24597850 PMCID: PMC4208604 DOI: 10.1089/ars.2014.5875] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
SIGNIFICANCE Heart disease is the primary cause of death in the industrialized world. Cardiac failure is dictated by an uncompensated reduction in the number of viable and fully functional cardiomyocytes. While current pharmacological therapies alleviate the symptoms associated with cardiac deterioration, heart transplantation remains the only therapy for advanced heart failure. Therefore, there is a pressing need for novel therapeutic modalities. Cell-based therapies involving cardiac stem cells (CSCs) constitute a promising emerging approach for the replenishment of the lost tissue and the restoration of cardiac contractility. RECENT ADVANCES CSCs reside in the adult heart and govern myocardial homeostasis and repair after injury by producing new cardiomyocytes and vascular structures. In the last decade, different classes of immature cells expressing distinct stem cell markers have been identified and characterized in terms of their growth properties, differentiation potential, and regenerative ability. Phase I clinical trials, employing autologous CSCs in patients with ischemic cardiomyopathy, are being completed with encouraging results. CRITICAL ISSUES Accumulating evidence concerning the role of CSCs in heart regeneration imposes a reconsideration of the mechanisms of cardiac aging and the etiology of heart failure. Deciphering the molecular pathways that prevent activation of CSCs in their environment and understanding the processes that affect CSC survival and regenerative function with cardiac pathologies, commonly accompanied by alterations in redox conditions, are of great clinical importance. FUTURE DIRECTIONS Further investigations of CSC biology may be translated into highly effective and novel therapeutic strategies aiming at the enhancement of the endogenous healing capacity of the diseased heart.
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Affiliation(s)
- Polina Goichberg
- Departments of Anesthesia and Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts
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Taegtmeyer H, Lubrano G. Rethinking cardiac metabolism: metabolic cycles to refuel and rebuild the failing heart. F1000PRIME REPORTS 2014; 6:90. [PMID: 25374668 PMCID: PMC4191265 DOI: 10.12703/p6-90] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The heart is a self-renewing biological pump that converts chemical energy into mechanical energy. The entire process of energy conversion is subject to complex regulation at the transcriptional, translational and post-translational levels. Within this system, energy transfer occurs with high efficiency, facilitated by a series of compound-conserved cycles. At the same time, the constituent myocardial proteins themselves are continuously made and degraded in order to adjust to changes in energy demand and changes in the extracellular environment. We recently have identified signals arising from intermediary metabolism that regulate the cycle of myocardial protein turnover. Using a new conceptual framework, we discuss the principle of metabolic cycles and their importance for refueling and for rebuilding the failing heart.
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Abstract
There is worldwide demand for therapies to promote the robust repair and regeneration with maximum regain of function of particular tissues and organs damaged by disease or injury. The potential role of adult stem cells has been highlighted by an increasing number of in vitro and in vivo studies. Nowhere is this more evident than in adult stem cell-based therapies being explored to promote cardiac regeneration. In spite of encouraging advances, significant challenges remain.
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Affiliation(s)
- Kursad Turksen
- Regenerative Medicine Program, Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada,
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Szibor M, Pöling J, Warnecke H, Kubin T, Braun T. Remodeling and dedifferentiation of adult cardiomyocytes during disease and regeneration. Cell Mol Life Sci 2014; 71:1907-16. [PMID: 24322910 PMCID: PMC11113405 DOI: 10.1007/s00018-013-1535-6] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2012] [Revised: 11/21/2013] [Accepted: 11/25/2013] [Indexed: 12/20/2022]
Abstract
Cardiomyocytes continuously generate the contractile force to circulate blood through the body. Imbalances in contractile performance or energy supply cause adaptive responses of the heart resulting in adverse rearrangement of regular structures, which in turn might lead to heart failure. At the cellular level, cardiomyocyte remodeling includes (1) restructuring of the contractile apparatus; (2) rearrangement of the cytoskeleton; and (3) changes in energy metabolism. Dedifferentiation represents a key feature of cardiomyocyte remodeling. It is characterized by reciprocal changes in the expression pattern of "mature" and "immature" cardiomyocyte-specific genes. Dedifferentiation may enable cardiomyocytes to cope with hypoxic stress by disassembly of the energy demanding contractile machinery and by reduction of the cellular energy demand. Dedifferentiation during myocardial repair might provide cardiomyocytes with additional plasticity, enabling survival under hypoxic conditions and increasing the propensity to enter the cell cycle. Although dedifferentiation of cardiomyocytes has been described during tissue regeneration in zebrafish and newts, little is known about corresponding mechanisms and regulatory circuits in mammals. The recent finding that the cytokine oncostatin M (OSM) is pivotal for cardiomyocyte dedifferentiation and exerts strong protective effects during myocardial infarction highlights the role of cytokines as potent stimulators of cardiac remodeling. Here, we summarize the current knowledge about transient dedifferentiation of cardiomyocytes in the context of myocardial remodeling, and propose a model for the role of OSM in this process.
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Affiliation(s)
- Marten Szibor
- Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany
- Research Program of Molecular Neurology, University of Helsinki, Helsinki, Finland
| | - Jochen Pöling
- Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany
- Department of Cardiac Surgery, Schüchtermann Clinic, Bad Rothenfelde, Germany
| | - Henning Warnecke
- Department of Cardiac Surgery, Schüchtermann Clinic, Bad Rothenfelde, Germany
| | - Thomas Kubin
- Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany
| | - Thomas Braun
- Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany
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Strategies affording prevascularized cell-based constructs for myocardial tissue engineering. Stem Cells Int 2014; 2014:434169. [PMID: 24511317 PMCID: PMC3913389 DOI: 10.1155/2014/434169] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Accepted: 12/02/2013] [Indexed: 12/20/2022] Open
Abstract
The production of a functional cardiac tissue to be transplanted in the injured area of the infarcted myocardium represents a challenge for regenerative medicine. Most cell-based grafts are unviable because of inadequate perfusion; therefore, prevascularization might be a suitable approach for myocardial tissue engineering. To this aim, cells with a differentiation potential towards vascular and cardiac muscle phenotypes have been cocultured in 2D or 3D appropriate scaffolds. In addition to these basic approaches, more sophisticated strategies have been followed employing mixed-cell sheets, microvascular modules, and inosculation from vascular explants. Technologies exerting spatial control of vascular cells, such as topographical surface roughening and ordered patterning, represent other ways to drive scaffold vascularization. Finally, microfluidic devices and bioreactors exerting mechanical stress have also been employed for high-throughput scaling-up production in order to accelerate muscle differentiation and speeding the endothelialization process. Future research should address issues such as how to optimize cells, biomaterials, and biochemical components to improve the vascular integration of the construct within the cardiac wall, satisfying the metabolic and functional needs of the myocardial tissue.
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Telukuntla KS, Suncion VY, Schulman IH, Hare JM. The advancing field of cell-based therapy: insights and lessons from clinical trials. J Am Heart Assoc 2013; 2:e000338. [PMID: 24113326 PMCID: PMC3835242 DOI: 10.1161/jaha.113.000338] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Kartik S Telukuntla
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL
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Abstract
The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions for the future development of large animal models to facilitate advances in stem cell-based regenerative medicine.
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Goldstein BJ, Hare JM, Lieberman S, Casiano R. Adult human nasal mesenchymal stem cells have an unexpected broad anatomic distribution. Int Forum Allergy Rhinol 2013; 3:550-5. [DOI: 10.1002/alr.21153] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Revised: 12/10/2012] [Accepted: 01/01/2013] [Indexed: 01/25/2023]
Affiliation(s)
| | - Joshua M. Hare
- Inderdisciplinary Stem Cell Institute; Miller School of Medicine; University of Miami; Miami; FL
| | - Seth Lieberman
- Department of Otolaryngology; Miller School of Medicine; University of Miami; Miami; FL
| | - Roy Casiano
- Department of Otolaryngology; Miller School of Medicine; University of Miami; Miami; FL
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