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

Mann, Brenda; West, Jennifer L.

doi:10.1002/ar.1116

Cited by 75 publications

(39 citation statements)

References 37 publications

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“…Despite a variety of prior strategies to tissue engineer elastin-rich constructs, [27][28][29][30] poor tropoelastin mRNA expression by adult cells have severely limited positive outcomes. 31,32 As mentioned in the Introduction, our ongoing study of HA cues for elastin regeneration is driven by prior work that suggested that several GAG types (HA, heparin sulfate) have roles in elastin synthesis, maturation, and organization in vivo.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

Kothapalli

Ramamurthi

2009

Tissue Engineering Part A

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Current efforts to tissue engineer elastin-rich vascular constructs and grafts are limited because of the poor elastogenesis of adult vascular smooth muscle cells (SMCs) and the unavailability of appropriate cues to upregulate and enhance cross-linking of elastin precursors (tropoelastin) into organized, mature elastin fibers. We earlier showed that hyaluronan (HA) fragments greatly enhance tropo-and matrix-elastin synthesis by SMCs, although the yield of matrix elastin is low. To improve matrix yields, here we investigate the benefits of adding copper (Cu 2+ ) ions (0.01 M and 0.1 M), concurrent with HA (756-2000 kDa), to enhance lysyl oxidase (LOX)-mediated elastin cross-linking machinery. Although absolute elastin amounts in test groups were not different from those in controls, on a per-cell basis, 0.1 M of Cu 2+ ions slowed cell proliferation (5.6 AE 2.3-fold increase over 21 days vs 22.9 AE 4.2-fold for non-additive controls), stimulated synthesis of collagen (4.1 AE 0.4-fold), tropoelastin (4.1 AE 0.05-fold) and cross-linked matrix elastin (4.2 ± 0.7-fold). LOX protein synthesis increased 2.5 times in the presence of 0.1 M of Cu 2+ ions, and these trends were maintained even in the presence of HA fragments, although LOX functional activity remained unchanged in all cases. The abundance of elastin and LOX in cell layers cultured with 0.1 M of Cu 2+ ions and HA fragments was qualitatively confirmed using immunoflourescence. Scanning electron microscopy images showed that SMC cultures supplemented with 0.1 M of Cu 2+ ions and HA oligomers and large fragments exhibited better deposition of mature elastic fibers (*1 mm diameter). However, 0.01 M of Cu 2+ ions did not have any beneficial effect on elastin regeneration. In conclusion, the results suggest that supplying 0.1 M of Cu 2+ ions to SMCs to concurrently (a) enhance per-cell yield of elastin matrix while allowing cells to remain viable and synthetic and not density-arrested in long-term culture because of their moderating effects on otherwise rapid cell proliferation and (b) provide additional benefits of enhanced elastin fiber formation and cross-linking within these tissue-engineered constructs.

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Section: Discussionmentioning

confidence: 99%

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

Kothapalli

Ramamurthi

2009

Tissue Engineering Part A

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“…Although groups have successfully fabricated membrane-like tisties limit cell growth (34). In addition, it is inherently difficult to correlate two-dimensional experiments to sues, such as heart valves (19), arteries (24), and skin (1), larger artificial tissues have been difficult to realize.…”

Section: Introductionmentioning

confidence: 99%

Directed Three-Dimensional Growth of Microvascular Cells and Isolated Microvessel Fragments

Chang

Hoying

2006

Cell Transplant

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Tissue engineering has promise as a means for repairing diseased and damaged tissues. A significant challenge in tissue construction relates to the constraints placed on tissue geometries resulting from diffusion limitations. An ability to incorporate a premade vasculature would overcome these difficulties and promote construct viability once implanted. Most in vitro microvascular fabrication strategies rely on surface-associated cell growth, manipulated cell monolayers, or random arrangement of cells within matrix materials. In contrast, we successfully suspended microvascular cells and isolated microvessel fragments within collagen and then microfluidically drove the mixtures into microfabricated network topologies. Developing within the 3D collagen matrix, patterned cells progressed into cord-like morphologies. These geometries were directed by the surrounding elastomer mold. With similar techniques, suspended fragments formed endothelial sprouts. By avoiding the addition of exogenous growth factors, we allowed constituent cells and fragments to autonomously develop within the constructs, providing a more physiologically relevant system for in vitro microvascular development. In addition, we present the first examples of directed endothelial cell sprouting from parent microvessel fragments. We believe this system may serve as a foundation for future in vivo fabrication of microvascular networks for tissue engineering applications.Key words: Microvascular; Tissue engineering; Microcirculation; Cell patterning INTRODUCTIONcellular matrix (ECM) (7) and synthetic proteins (37). Although cells attach to these microfabricated surfaces and grow on the designed patterns, the techniques have Researchers are developing a variety of tissue engineered (TE) constructs, incorporating various cellular presented problems. In some instances, heterogeneous surface treatments and nonconformal substrate propergenotypes within biocompatible materials (13). Although groups have successfully fabricated membrane-like tisties limit cell growth (34). In addition, it is inherently difficult to correlate two-dimensional experiments to sues, such as heart valves (19), arteries (24), and skin (1), larger artificial tissues have been difficult to realize. three-dimensional systems (36). Other researchers have focused efforts developing in vitro three-dimensional Engineered tissue development has been hindered by diffusion limitations of construct geometries; constituent (3D) microvascular systems. In these constructs, cells are suspended in a 3D scaffold or matrix and spontanecells lack adequate transport of oxygen, nutrients, and wastes to maintain viability (5). Future artificial organs ously organize into cords or capillary-like structures in vitro (6). This behavior is often induced by doping mawill require prevascularization to rapidly perfuse the constructs and efficiently meet the metabolic needs of trices with growth factors and/or ECM proteins (3,6,9,17,21,29,33). Within these 3D environments, vascular the incorporated cells once ...

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“…Several different approaches in cell transplantation and cardiac tissue engineering have emerged as potential treatments to restore cardiac function. 1 Implantation of skeletal muscle cells, bone marrow cells, mesenchymal stem cells, or myoblasts has been reported to stimulate revascularization of ischemic heart tissue and enhance cardiac function. 2,3 In addition, cell-seeded grafts have been proposed for in vitro cardiac tissue growth and subsequent in vivo transplantation.…”

mentioning

confidence: 99%

Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

et al. 2005

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Background-Promoting survival of transplanted cells or endogenous precursors is an important goal. We hypothesized that a novel approach to promote vascularization would be to create injectable microenvironments within the myocardium that recruit endothelial cells and promote their survival and organization. Methods and Results-In this study we demonstrate that self-assembling peptides can be injected and that the resulting nanofiber microenvironments are readily detectable within the myocardium. Furthermore, the self-assembling peptide nanofiber microenvironments recruit progenitor cells that express endothelial markers, as determined by staining with isolectin and for the endothelial-specific protein platelet-endothelial cell adhesion molecule-1. Vascular smooth muscle cells are recruited to the microenvironment and appear to form functional vascular structures. After the endothelial cell population, cells that express ␣-sarcomeric actin and the transcription factor Nkx2.5 infiltrate the peptide microenvironment. When exogenous donor green fluorescent protein-positive neonatal cardiomyocytes were injected with the self-assembling peptides, transplanted cardiomyocytes in the peptide microenvironment survived and also augmented endogenous cell recruitment. Conclusions-These experiments demonstrate that self-assembling peptides can create nanofiber microenvironments in the myocardium and that these microenvironments promote vascular cell recruitment. Because these peptide nanofibers may be modified in a variety of ways, this approach may enable injectable tissue regeneration strategies.

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

Cited by 75 publications

References 37 publications

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

Directed Three-Dimensional Growth of Microvascular Cells and Isolated Microvessel Fragments

Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells

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