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Minimally invasive cell-seeded biomaterial systems for injectable/epicardial implantation in ischemic heart disease.

Ravichandran R, Venugopal JR, Sundarrajan S, Mukherjee S, Ramakrishna S - Int J Nanomedicine (2012)

Bottom Line: These devices and acellular/cellular cardiac patches are employed surgically and sutured to the epicardial surface of the heart, limiting the region of therapeutic benefit.An injectable system offers the potential benefit of minimally invasive release into the myocardium either to restore the injured extracellular matrix or to act as a scaffold for cell delivery.This review summarizes the growing body of literature in the field of myocardial tissue engineering, where biomaterial injection, with or without simultaneous cellular delivery, has been pursued to enhance functional and structural outcomes following MI.

View Article: PubMed Central - PubMed

Affiliation: Healthcare and Energy Materials Laboratory, National University of Singapore, Singapore.

ABSTRACT
Myocardial infarction (MI) is characterized by heart-wall thinning, myocyte slippage, and ventricular dilation. The injury to the heart-wall muscle after MI is permanent, as after an abundant cell loss the myocardial tissue lacks the intrinsic capability to regenerate. New therapeutics are required for functional improvement and regeneration of the infarcted myocardium, to overcome harmful diagnosis of patients with heart failure, and to overcome the shortage of heart donors. In the past few years, myocardial tissue engineering has emerged as a new and ambitious approach for treating MI. Several left ventricular assist devices and epicardial patches have been developed for MI. These devices and acellular/cellular cardiac patches are employed surgically and sutured to the epicardial surface of the heart, limiting the region of therapeutic benefit. An injectable system offers the potential benefit of minimally invasive release into the myocardium either to restore the injured extracellular matrix or to act as a scaffold for cell delivery. Furthermore, intramyocardial injection of biomaterials and cells has opened new opportunities to explore and also to augment the potentials of this technique to ease morbidity and mortality rates owing to heart failure. This review summarizes the growing body of literature in the field of myocardial tissue engineering, where biomaterial injection, with or without simultaneous cellular delivery, has been pursued to enhance functional and structural outcomes following MI. Additionally, this review also provides a complete outlook on the tissue-engineering therapies presently being used for myocardial regeneration, as well as some perceptivity into the possible issues that may hinder its progress in the future.

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(A) An AV loop was constructed and placed into the tissue engineering chamber in the nude rat groin. (B) Cells (ASC–rCM or ASC or rCM) suspended in Matrigel™ were seeded around the AV loop.Reprinted from Biomaterials. Choi YS, Matsuda K, Dusting GJ, Morrison WA, Dilley RJ. Engineering cardiac tissue in vivo from human adipose-derived stem cells. 31:2236–2242. Copyright 2010 with permission from Elsevier.99
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f4-ijn-7-5969: (A) An AV loop was constructed and placed into the tissue engineering chamber in the nude rat groin. (B) Cells (ASC–rCM or ASC or rCM) suspended in Matrigel™ were seeded around the AV loop.Reprinted from Biomaterials. Choi YS, Matsuda K, Dusting GJ, Morrison WA, Dilley RJ. Engineering cardiac tissue in vivo from human adipose-derived stem cells. 31:2236–2242. Copyright 2010 with permission from Elsevier.99

Mentions: Planat-Benard and colleagues found that beating cells with cardiomyocyte characteristics could be noticed after ASC culture. The cardiomyocyte phenotype was initially noticed by morphological observation and further confirmed with expression of cardiac-specific marker proteins by immunocytochemistry and ultrastructural analysis, revealing the presence of ventricle and atrial-like cells. Electrophysiological studies on early culture demonstrated pacemaker activity of these cells.94 Additionally, the same group showed that adipose lineage cells function as progenitors for endothelial cells. They were reported to take part in vascular-like structure configuration in Matrigel plug and improve neovascularization in ischemic heart tissue.95 This opens novel perspectives on angiogenic therapy based on the injection of ASCs for treatment of MI.98 Recently, there has been a growing body of literature demonstrating spontaneous differentiation of ASCs into active cardiomyocyte like cells without treatment with chemicals like 5-azacytidine both in in vitro94 and animal studies.99 Similarly, it was suggested that even though there was poor engraftment of intramyocardial delivery postinfarction of freshly isolated ASC, they showed good therapeutic effect on heart functionality in rats by means of proangiogenic effect.100 A later study demonstrated the utilization of a tissue-engineering chamber that incorporates an arteriovenous loop for the generation of human cardiac muscle cells in vivo from ASCs cocultured with rat cardiomyocytes (rCMs) as shown in Figure 4.99 After 6 weeks of implantation, the ASC/rCM coimplantation allowed spontaneous differentiation of ASCs into cardiac cells, adipocytes, and smooth-muscle cells in the rat groin. This methodology successfully produced a considerable amount of vascularized human cardiac tissue. Nevertheless, to improve its clinical relevance, it is essential to have a thorough understanding of the mechanisms involved in ASC differentiation to cardiomyogenic lineage, so that autologous ASCs into cardiac tissue can be made without the requirement of rCM coculture and unwanted differentiation to adipogenic lineage can be avoided for CTE applications.


Minimally invasive cell-seeded biomaterial systems for injectable/epicardial implantation in ischemic heart disease.

Ravichandran R, Venugopal JR, Sundarrajan S, Mukherjee S, Ramakrishna S - Int J Nanomedicine (2012)

(A) An AV loop was constructed and placed into the tissue engineering chamber in the nude rat groin. (B) Cells (ASC–rCM or ASC or rCM) suspended in Matrigel™ were seeded around the AV loop.Reprinted from Biomaterials. Choi YS, Matsuda K, Dusting GJ, Morrison WA, Dilley RJ. Engineering cardiac tissue in vivo from human adipose-derived stem cells. 31:2236–2242. Copyright 2010 with permission from Elsevier.99
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526148&req=5

f4-ijn-7-5969: (A) An AV loop was constructed and placed into the tissue engineering chamber in the nude rat groin. (B) Cells (ASC–rCM or ASC or rCM) suspended in Matrigel™ were seeded around the AV loop.Reprinted from Biomaterials. Choi YS, Matsuda K, Dusting GJ, Morrison WA, Dilley RJ. Engineering cardiac tissue in vivo from human adipose-derived stem cells. 31:2236–2242. Copyright 2010 with permission from Elsevier.99
Mentions: Planat-Benard and colleagues found that beating cells with cardiomyocyte characteristics could be noticed after ASC culture. The cardiomyocyte phenotype was initially noticed by morphological observation and further confirmed with expression of cardiac-specific marker proteins by immunocytochemistry and ultrastructural analysis, revealing the presence of ventricle and atrial-like cells. Electrophysiological studies on early culture demonstrated pacemaker activity of these cells.94 Additionally, the same group showed that adipose lineage cells function as progenitors for endothelial cells. They were reported to take part in vascular-like structure configuration in Matrigel plug and improve neovascularization in ischemic heart tissue.95 This opens novel perspectives on angiogenic therapy based on the injection of ASCs for treatment of MI.98 Recently, there has been a growing body of literature demonstrating spontaneous differentiation of ASCs into active cardiomyocyte like cells without treatment with chemicals like 5-azacytidine both in in vitro94 and animal studies.99 Similarly, it was suggested that even though there was poor engraftment of intramyocardial delivery postinfarction of freshly isolated ASC, they showed good therapeutic effect on heart functionality in rats by means of proangiogenic effect.100 A later study demonstrated the utilization of a tissue-engineering chamber that incorporates an arteriovenous loop for the generation of human cardiac muscle cells in vivo from ASCs cocultured with rat cardiomyocytes (rCMs) as shown in Figure 4.99 After 6 weeks of implantation, the ASC/rCM coimplantation allowed spontaneous differentiation of ASCs into cardiac cells, adipocytes, and smooth-muscle cells in the rat groin. This methodology successfully produced a considerable amount of vascularized human cardiac tissue. Nevertheless, to improve its clinical relevance, it is essential to have a thorough understanding of the mechanisms involved in ASC differentiation to cardiomyogenic lineage, so that autologous ASCs into cardiac tissue can be made without the requirement of rCM coculture and unwanted differentiation to adipogenic lineage can be avoided for CTE applications.

Bottom Line: These devices and acellular/cellular cardiac patches are employed surgically and sutured to the epicardial surface of the heart, limiting the region of therapeutic benefit.An injectable system offers the potential benefit of minimally invasive release into the myocardium either to restore the injured extracellular matrix or to act as a scaffold for cell delivery.This review summarizes the growing body of literature in the field of myocardial tissue engineering, where biomaterial injection, with or without simultaneous cellular delivery, has been pursued to enhance functional and structural outcomes following MI.

View Article: PubMed Central - PubMed

Affiliation: Healthcare and Energy Materials Laboratory, National University of Singapore, Singapore.

ABSTRACT
Myocardial infarction (MI) is characterized by heart-wall thinning, myocyte slippage, and ventricular dilation. The injury to the heart-wall muscle after MI is permanent, as after an abundant cell loss the myocardial tissue lacks the intrinsic capability to regenerate. New therapeutics are required for functional improvement and regeneration of the infarcted myocardium, to overcome harmful diagnosis of patients with heart failure, and to overcome the shortage of heart donors. In the past few years, myocardial tissue engineering has emerged as a new and ambitious approach for treating MI. Several left ventricular assist devices and epicardial patches have been developed for MI. These devices and acellular/cellular cardiac patches are employed surgically and sutured to the epicardial surface of the heart, limiting the region of therapeutic benefit. An injectable system offers the potential benefit of minimally invasive release into the myocardium either to restore the injured extracellular matrix or to act as a scaffold for cell delivery. Furthermore, intramyocardial injection of biomaterials and cells has opened new opportunities to explore and also to augment the potentials of this technique to ease morbidity and mortality rates owing to heart failure. This review summarizes the growing body of literature in the field of myocardial tissue engineering, where biomaterial injection, with or without simultaneous cellular delivery, has been pursued to enhance functional and structural outcomes following MI. Additionally, this review also provides a complete outlook on the tissue-engineering therapies presently being used for myocardial regeneration, as well as some perceptivity into the possible issues that may hinder its progress in the future.

Show MeSH
Related in: MedlinePlus