Survival and Function of Bioengineered Cardiac Grafts

Li, Ren‐Ke; Jia, Zhiqiang; Weisel, Richard D.; Mickle, Donald A.G.; Choi, Angel; Yau, Terrence M.

doi:10.1161/01.cir.100.suppl_2.ii-63

Cited by 249 publications

(209 citation statements)

References 7 publications

(2 reference statements)

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“…Three-dimensional cardiac tissue constructs that express structural and physiological features characteristic of native cardiac muscle have been engineered in vitro using fetal or neonatal rat cardiac myocytes (CMs) on collagen fibers 2 , fibrous polyglycolic acid scaffolds [3][4][5][6][7] and porous collagen scaffolds [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

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Cardiac tissue engineering using perfusion bioreactor systems

et al. 2008

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This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is 'biomimetic' in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2-4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and highfidelity models for biological research.

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Section: Introductionmentioning

confidence: 99%

“…In early studies, cells were seeded onto scaffolds and cultivated in dishes 4,7,8,11 , in spinner flasks 3,4,7 or in rotating vessels 2,4,7 . Inallof these systems, oxygen dissolved in culture medium was transported to the cells by molecular diffusion.…”

Section: Introductionmentioning

confidence: 99%

Cardiac tissue engineering using perfusion bioreactor systems

et al. 2008

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“…Delivery of cells in tissue-like structures that preserve cellular attachments could increase cell delivery efficiency and reduce cell death (4). Most heart tissue engineered in vitro to date has focused on creating tissues by seeding neonatal rat or chick cardiomyocytes into polymer or extracellular matrix scaffolds and gels (5)(6)(7)(8)(9)(10)(11). Creation of 3D tissues that are composed only of cells and the matrix they secrete (12)(13)(14)(15), which we refer to as ''scaffoldfree'' tissue engineering, addresses limitations associated with polymer and exogenous matrix-based tissues (e.g., unfavorable host response to biomaterials).…”

mentioning

confidence: 99%

Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue

Stevens

Kreutziger

Dupras

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

380

329

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Success of human myocardial tissue engineering for cardiac repair has been limited by adverse effects of scaffold materials, necrosis at the tissue core, and poor survival after transplantation due to ischemic injury. Here, we report the development of scaffold-free prevascularized human heart tissue that survives in vivo transplantation and integrates with the host coronary circulation. Human embryonic stem cells (hESCs) were differentiated to cardiomyocytes by using activin A and BMP-4 and then placed into suspension on a rotating orbital shaker to create human cardiac tissue patches. Optimization of patch culture medium significantly increased cardiomyocyte viability in patch centers. These patches, composed only of enriched cardiomyocytes, did not survive to form significant grafts after implantation in vivo. To test the hypothesis that ischemic injury after transplantation would be attenuated by accelerated angiogenesis, we created ''second-generation,'' prevascularized, and entirely human patches from cardiomyocytes, endothelial cells (both human umbilical vein and hESC-derived endothelial cells), and fibroblasts. Functionally, vascularized patches actively contracted, could be electrically paced, and exhibited passive mechanics more similar to myocardium than patches comprising only cardiomyocytes. Implantation of these patches resulted in 10-fold larger cell grafts compared with patches composed only of cardiomyocytes. Moreover, the preformed human microvessels anastomosed with the rat host coronary circulation and delivered blood to the grafts. Thus, inclusion of vascular and stromal elements enhanced the in vitro performance of engineered human myocardium and markedly improved viability after transplantation. These studies demonstrate the importance of including vascular and stromal elements when designing human tissues for regenerative therapies.angiogenesis ͉ human embryonic stem cells ͉ tissue engineering ͉ myocardial infarction ͉ cardiomyocyte

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“…These cells survived and formed new tissue that resembled cardiac muscle at the site of injury. Similar studies have been performed by using embryonic cardiac myocytes (Soonpaa et al, 1994), myoblast cell lines (Koh et al, 1993), and cardiomyocytes, smooth muscle cells, and fibroblasts seeded onto scaffolds (Li et al, 1999(Li et al, , 2000Carrier et al, 1999). Carrier et al (1999) have also begun to look at the influence of seeding conditions and different bioreactors when culturing seeded scaffolds.…”

Section: Cardiac Musclementioning

confidence: 89%

Tissue engineering in the cardiovascular system: Progress toward a tissue engineered heart

Mann

West

2001

Anat. Rec.

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Achieving the lofty goal of developing a tissue engineered heart will likely rely on progress in engineering the various components: blood vessels, heart valves, and cardiac muscle. Advances in tissue engineered vascular grafts have shown the most progress to date. Research in tissue-engineered vascular grafts has focused on improving scaffold design, including mechanical properties and bioactivity; genetically engineering cells to improve graft performance; and optimizing tissue formation through in vitro mechanical conditioning. Some of these same approaches have been used in developing tissue engineering heart valves and cardiac muscle as well. Continued advances in scaffold technology and a greater understanding of vascular cell biology along with collaboration among engineers, scientists, and physicians will lead to further progress in the field of cardiovascular tissue engineering and ultimately the development of a tissue-engineered heart.

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Survival and Function of Bioengineered Cardiac Grafts

Cited by 249 publications

References 7 publications

Cardiac tissue engineering using perfusion bioreactor systems

Cardiac tissue engineering using perfusion bioreactor systems

Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue

Tissue engineering in the cardiovascular system: Progress toward a tissue engineered heart

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