Bioengineering Heart Muscle: A Paradigm for Regenerative Medicine

Vunjak-Novakovic, Gordana; Lui, Kathy O.; Tandon, Nina; Chien, Kenneth R.

doi:10.1146/annurev-bioeng-071910-124701

Cited by 169 publications

(130 citation statements)

References 116 publications

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“…Although the adult human heart is no longer considered a static organ unable to replace its parenchymal cells during the course of life, the rate of myocyte regeneration reported thus far varies dramatically. Minimal levels of myocyte turnover, which decrease with age, have been claimed (1)(2)(3)(4)(5), but results have also been obtained supporting continuous myocyte renewal at a remarkable degree (6)(7)(8)(9)(10)(11)(12). Independent from the extent of the process, the debate is further intensified by contrasting views regarding the origin of newly formed cardiomyocytes (13,14).…”

Section: Introductionmentioning

confidence: 99%

Regenerating new heart with stem cells

Anversa

Kajstura²,

Rota³

et al. 2013

J. Clin. Invest.

142

126

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This article discusses current understanding of myocardial biology, emphasizing the regeneration potential of the adult human heart and the mechanisms involved. In the last decade, a novel conceptual view has emerged. The heart is no longer considered a postmitotic organ, but is viewed as a self-renewing organ characterized by a resident stem cell compartment responsible for tissue homeostasis and cardiac repair following injury. Additionally, HSCs possess the ability to transdifferentiate and acquire the cardiomyocyte, vascular endothelial, and smooth muscle cell lineages. Both cardiac and hematopoietic stem cells may be used therapeutically in an attempt to reverse the devastating consequences of chronic heart failure of ischemic and nonischemic origin. IntroductionOur understanding of the process of myocardial regeneration is currently under debate. Although the adult human heart is no longer considered a static organ unable to replace its parenchymal cells during the course of life, the rate of myocyte regeneration reported thus far varies dramatically. Minimal levels of myocyte turnover, which decrease with age, have been claimed (1-5), but results have also been obtained supporting continuous myocyte renewal at a remarkable degree (6-12). Independent from the extent of the process, the debate is further intensified by contrasting views regarding the origin of newly formed cardiomyocytes (13,14). These issues have important implications because knowledge of the magnitude of cell regeneration and the mechanisms involved may offer a novel dynamic perspective of cardiac homeostasis and myocardial biology. This information is critical for the identification of strategies aiming at the restoration of the functional and structural integrity of the failing human heart.The recognition that the adult heart harbors a compartment of multipotent c-kit-positive cardiac stem cells (CSCs) (15-23) and other progenitor cell classes (24-29) capable of differentiating into cardiomyocytes and coronary vessels has raised the challenging question concerning their embryologic origin and role in cardiac cell turnover and regeneration. CSCs are stored in interstitial structures with the characteristics of stem cell niches and can divide symmetrically and asymmetrically, with the ability to self-renew and form a committed progeny (17,21,30). But whether this stem cell pool is actually self-autonomous and fully distinct from HSCs in the bone marrow remains to be determined. c-kit-positive HSCs transdifferentiate and acquire the myocyte, endothelial cell, and smooth muscle cell lineage (31), suggesting that the bone marrow participates in the homeostatic control of the myocardium and the restoration of myocytes and coronary vessels following injury. Additionally, the possibility has been advanced that postmitotic myocytes dedifferentiate, acquire an immature cell phenotype, and then reenter the cell cycle and divide (32-35), representing an alternative or complementary modality of myocyte formation. In this Review, we discuss CSCs, HS...

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Section: Introductionmentioning

confidence: 99%

Regenerating new heart with stem cells

Anversa

Kajstura²,

Rota³

et al. 2013

J. Clin. Invest.

142

126

View full text Add to dashboard Cite

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“…With the enormous progress made in largescale derivation of cardiomyocytes from human PSCs, additional progress in tissue engineering is required to improve the function, engrafting, survival, electromechanical integration and delivery of engineered cardiac tissue for use in transplantation therapies. At the same time, more advanced engineered cardiac tissue would provide for better drug screening and patient-specific disease modeling in vitro (further reviewed by Cimetta et al, 2013;Hirt et al, 2014;Vunjak-Novakovic et al, 2011).…”

Section: Direct Lineage Conversion Of Somatic Cells Into Cardiomyocytesmentioning

confidence: 99%

How to make a cardiomyocyte

et al. 2014

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During development, cardiogenesis is orchestrated by a family of heart progenitors that build distinct regions of the heart. Each region contains diverse cell types that assemble to form the complex structures of the individual cardiac compartments. Cardiomyocytes are the main cell type found in the heart and ensure contraction of the chambers and efficient blood flow throughout the body. Injury to the cardiac muscle often leads to heart failure due to the loss of a large number of cardiomyocytes and its limited intrinsic capacity to regenerate the damaged tissue, making it one of the leading causes of morbidity and mortality worldwide. In this Primer we discuss how insights into the molecular and cellular framework underlying cardiac development can be used to guide the in vitro specification of cardiomyocytes, whether by directed differentiation of pluripotent stem cells or via direct lineage conversion. Additional strategies to generate cardiomyocytes in situ, such as reactivation of endogenous cardiac progenitors and induction of cardiomyocyte proliferation, will also be discussed.

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“…At the milli-scale level, aligned myofibers are induced by matrix anisotropy while across the transmural direction, varying spatial arrangement of myofibers is present [26] . In the micro-scale, vascularization is needed as support system for nutrient/waste exchange in highly densed native myocardium [27] . The design considerations are summarized in Figure 1.…”

Section: Design Considerationsmentioning

confidence: 99%

Bioprinting in cardiovascular tissue engineering: a review

Lee¹,

Sing²,

Tan³

et al. 2016

ijb

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Fabrication techniques for cardiac tissue engineering have been evolving around scaffold-based and scaffold-free approaches. Conventional fabrication approaches lack control over scalability and homogeneous cell distribution. Bioprinting provides a technological platform for controlled deposition of biomaterials, cells, and biological factors in an organized fashion. Bioprinting is capable of alternating heterogeneous cell printing, printing anatomical relevant structure and microchannels resembling vasculature network. These are essential features of an engineered cardiac tissue. Bioprinting can potentially build engineered cardiac construct that resembles native tissue across macro to nanoscale.

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Bioengineering Heart Muscle: A Paradigm for Regenerative Medicine

Cited by 169 publications

References 116 publications

Regenerating new heart with stem cells

Regenerating new heart with stem cells

How to make a cardiomyocyte

Bioprinting in cardiovascular tissue engineering: a review

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