Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

Harpa, Marius; Movileanu, Ionela; Sierad, Leslie Neil; Cotoi, Ovidiu Simion; Suciu, Horaţiu; Sircuța, Carmen; Preda, Terezia; Nistor, Dan; Brânzaniuc, Klara; Deac, Radu; Dandel, Michael; Gurzu, Simona; Harceaga, Lucian; Olah, Peter; Simionescu, Anca A.; Simionescu, Dan T.

doi:10.1515/rrlm-2015-0046

Cited by 7 publications

(10 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we started with n=6 for the ASC-seeded valves, their progressive covering with fibrous tissue, development of right ventricular insufficiency, and humane considerations forced us to euthanize several animals before the targeted time point. Similar results have been obtained recently by our group using ASC-seeded acellular pulmonary valves (10), pointing to a causal relationship between stem cell seeding and tissue overgrowth in the sheep. Clearly, additional studies with larger sample sizes and more detailed tracking of the fate of ASCs after implantation are needed to answer some of the above-mentioned questions.…”

Section: Discussion Conclusion and Limitationssupporting

confidence: 90%

In Vivo Testing of Xenogeneic Acellular Aortic Valves Seeded with Stem Cells

Harpa

Movileanu

Sierad³

et al. 2016

Revista Romana De Medicina De Laborator

Self Cite

View full text Add to dashboard Cite

Section: Discussion Conclusion and Limitationssupporting

confidence: 90%

In Vivo Testing of Xenogeneic Acellular Aortic Valves Seeded with Stem Cells

Harpa

Movileanu

Sierad³

et al. 2016

Revista Romana De Medicina De Laborator

Self Cite

View full text Add to dashboard Cite

“…Despite exposing bare collagen surfaces to flowing blood, we could not detect any thrombus structures in any of the explants, and there was no need for systemic anticoagulation. Notably, TEHVs can be considered tissue-derived bioprostheses heart valves, which, according to current clinical guidelines, require oral anticoagulation with Vitamin K antagonists for 3 months postoperation ( 9 ). In pilot studies, we explanted two acellular valves: one was explanted early (after 48 h) and a second after 7 days, both due to non-valve-related issues.…”

Section: Discussionmentioning

confidence: 99%

“…Studies of synthetic (polymeric) scaffolds seeded with endothelial cells and myofibroblasts ( 8 ) showed that the presence of repopulating cells was associated with valvular insufficiency secondary to cusps remodeling and retraction. Scaffolds seeded with autologous stem cells ( 9 ), or just endothelial cells ( 10 ), also revealed multiple drawbacks, a major one being the fibrosis and contraction of the cusps, induced by the seeded cells ( 9 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

Movileanu

Harpa

Harceaga

et al. 2021

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries.Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls.Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold.Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology.

show abstract

“…2-d) the ADSCs being isolated and cultured in vitro as described by Zuk (2001) [29] and Gimble (2003) [3] for subsequent use in heart valves tissue regeneration. The ability of isolated cells to differentiate into multiple cell lines has been demonstrated by using differentiation kits (PromoCell, Inc) containing mixtures of growth factors causing adult stem cells to differentiate separately in adipocytes, osteoblasts and chondrocytes, this part of the research being described in another study published by our research team [30].…”

Section: Experimental Part Materials and Methodsmentioning

confidence: 99%

Minimally Invasive Surgical Protocol for Adipose Derived Stem Cells Collection and Isolation - Ovine Model

Hussein¹,

Harpa²,

Movileanu³

et al. 2019

Rev. Chim.

Self Cite

View full text Add to dashboard Cite

Many methods of stem cells collection and isolation from various tissue types harvested either from small or large experimental animals or from human tissues have been published so far, all evaluating them as a potential source of adult mesenchymal stem cells with applicability in various pathologies or tissue bioengineering. The present study purposed to describe a minimally invasive surgical protocol for adipose tissue collection from sheep�s inter-scapular area. The procedure was carried out on adult sheeps, in aseptic conditions. A light sedation protocol with Detomidine was performed, the recovery from anesthesia being carried out with Atipamezole. Throughout the sedation, the surgical procedure and the recovery from anesthesia, the vital functions of the animal were monitored. The adipose tissue samples collected in sterile tubes with culture medium (Dulbecco�s modified Eagle�s medium - DMEM/10% / FBS10 - fetal bovine serum, 2% antibiotic/antifungal), have been succesfully used by our research team for adipose tissue derived stem cells (ADSCs) isolation for further use in cardiac valves tissue engineering.

show abstract

Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

Cited by 7 publications

References 35 publications

In Vivo Testing of Xenogeneic Acellular Aortic Valves Seeded with Stem Cells

In Vivo Testing of Xenogeneic Acellular Aortic Valves Seeded with Stem Cells

Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

Minimally Invasive Surgical Protocol for Adipose Derived Stem Cells Collection and Isolation - Ovine Model

Contact Info

Product

Resources

About