Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

Zilla, Peter; Deutsch, Manfred; Bezuidenhout, Deon; Davies, Neil; Pennel, Timothy

doi:10.3389/fcvm.2020.00159

Cited by 23 publications

(32 citation statements)

References 376 publications

(521 reference statements)

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“…This result was comparable to tube formation data from cardiac pericytes; however, intriguingly the angiogenic paracrine effect of NG2 UCPs appears superior (14). This may be due to the high secretion of ANGPT-2 seen in cardiac pericytes, which in the absence of angiogenic stimulation results in vessel regression (31). Additionally, data indicates that NG2 UCPs may help facilitate the development of a graft endothelial layer.…”

Section: Discussionsupporting

confidence: 77%

Umbilical Cord Pericytes Provide a Viable Alternative to Mesenchymal Stem Cells for Neonatal Vascular Engineering

Cathery

Faulkner

Jover

et al. 2021

Front. Cardiovasc. Med.

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Reconstructive surgery of congenital heart disease (CHD) remains inadequate due to the inability of prosthetic grafts to match the somatic growth of pediatric patients. Functionalization of grafts with mesenchymal stem cells (MSCs) may provide a solution. However, MSCs represent a heterogeneous population characterized by wide diversity across different tissue sources. Here we investigated the suitability of umbilical cord pericytes (UCPs) in neonatal vascular engineering. Explant outgrowth followed by immunomagnetic sorting was used to isolate neural/glial antigen 2 (NG2)+/CD31− UCPs. Expanded NG2 UCPs showed consistent antigenic phenotype, including expression of mesenchymal and stemness markers, and high proliferation rate. They could be induced to a vascular smooth muscle cell-like phenotype after exposure to differentiation medium, as evidenced by the expression of transgelin and smooth muscle myosin heavy chain. Analysis of cell monolayers and conditioned medium revealed production of extracellular matrix proteins and the secretion of major angiocrine factors, which conferred UCPs with ability to promote endothelial cell migration and tube formation. Decellularized swine-derived grafts were functionalized using UCPs and cultured under static and dynamic flow conditions. UCPs were observed to integrate into the outer layer of the graft and modify the extracellular environment, resulting in improved elasticity and rupture strain in comparison with acellular grafts. These findings demonstrate that a homogeneous pericyte-like population can be efficiently isolated and expanded from human cords and integrated in acellular grafts currently used for repair of CHD. Functional assays suggest that NG2 UCPs may represent a viable option for neonatal tissue engineering applications.

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Section: Discussionsupporting

confidence: 77%

Umbilical Cord Pericytes Provide a Viable Alternative to Mesenchymal Stem Cells for Neonatal Vascular Engineering

Cathery

Faulkner

Jover

et al. 2021

Front. Cardiovasc. Med.

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“…Improving our understanding of the biomechanical, cellular, and molecular pathways underlying neotissue formation in TEVGs holds the key to improving their performance through rational design. A lack of effective and correlative biological implantation models hinders the translation of tissue engineering findings, as the differences in geometry, mechanics, and biological signaling between humans and research animals must be considered 30 . A history of empiric design changes and studies using a small number of animal models has made comparisons between studies difficult and further hinders a mechanistic understanding of tissue engineering paradigms 31 .…”

Section: Discussionmentioning

confidence: 99%

Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering

Blum

Roby

Zbinden

et al. 2021

Sci Rep

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Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.

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“…Fall‐out and transmural cell growth remain the two prospective mechanisms, which need to be validated in larger animals for longer grafts before implementing arterial TEVGs in humans. [ 5 ] Multiple research groups worldwide have ventured into identifying a suitable TEVG target for arterial regeneration in large animal models (porcine, ovine, and canine), which was reviewed recently. [ 204 ] The key hurdles for larger grafts are thrombosis and loss of mechanical properties over time.…”

Section: Concluding Remarks Challenges and Future Perspectivesmentioning

confidence: 99%

“…The reason behind the poor performance of synthetic grafts is compliance mismatch and their non‐biological composition. [ 5 ] Researchers are venturing into the surface modification of these grafts to prevent thrombosis. [ 6 ] Amidst all the success, if we look at the vascular graft market with a clinical perspective, limited innovative products are coming up with the ever‐persistent inability of synthetic grafts for smaller vessel replacement.…”

Section: Introductionmentioning

confidence: 99%

Tissue‐Engineered Vascular Grafts: Emerging Trends and Technologies

Gupta

Mandal

2021

Adv Funct Materials

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Vascular tissue engineering has made prodigious progress in recent years by converging multidisciplinary approaches. Latest technological advancements foster the development of next‐generation tissue‐engineered vascular grafts (TEVGs) for treating various vasculopathies. While traditional therapeutic methods rely on bypassing the severely damaged vessels with synthetic counterparts with no growth potential, contemporary perspectives focus on biodegradable conduits bestowing an inherent remodeling capability. This review highlights emerging innovative trends and technologies adopted to pragmatically fulfill current scientific needs while improving overall TEVG performance in pre‐clinical and clinical settings. A comprehensive overview of various milestones achieved in the past few decades is first summarized, followed by an appraisal of the significant hurdles for clinical translation. The latest techniques to rationally address critical challenges, viz., intimal hyperplasia, thrombosis, constructive graft remodeling, and adequate neo‐tissue formation are discussed. Finally, an update on ongoing clinical trials is provided and future perspectives required to persuade TEVGs to become a clinical reality are delineated.

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Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

Cited by 23 publications

References 376 publications

Umbilical Cord Pericytes Provide a Viable Alternative to Mesenchymal Stem Cells for Neonatal Vascular Engineering

Umbilical Cord Pericytes Provide a Viable Alternative to Mesenchymal Stem Cells for Neonatal Vascular Engineering

Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering

Tissue‐Engineered Vascular Grafts: Emerging Trends and Technologies

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