Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates

Abstract

Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prostheses.

How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes

“…Despite the encouraging results obtained with preseeded scaffolds in sheep and baboons (Vincentelli et al 2007;Weber et al 2011), the antithrombogenic properties of MSCs (Hashi et al 2007) and their ability to stimulate in vivo endothelialization (Mirza et al 2008) should preclude future requirements for preseeding with endothelial cells.…”

Adipose Derived Tissue Engineered Heart Valve

“…However, in vitro endothelialization of grafts involves multiple additional procedures, for instance donation of patient specific tissue for isolation of endothelial cells. In vivo studies showed that implantation of nonendothelialized TEHV resulted in almost confluent endothelialization already after 4-8 weeks in vivo [16,48,50,51]. However, using ADSC for tissue engineering would enable the endothelialization after differentiation of the cells in the presence of vascular endothelial growth factor without requiring any surgical harvesting of additional patientspecific tissues.…”

“…A major focus in heart valve tissue engineering is the in vitro creation of mature tissue structures compliant with native valve functionality. Various cell types have been investigated for their suitability for heart valve tissue engineering including high remodeling capacity of the Extracellular Matrix (ECM), including prenatal cells [11][12][13], umbilical cord [14][15][16] and vascular derived cells [17][18][19]. Furthermore the observed multipotency of adult Mesenchymal Stem Cells (MSCs) including their ability to differentiate into cells found in the adult heart, such as cardiomyocytes and endothelial cells, sparked interest to develop them for future cell-based therapy such as heart valve engineering.…”

“…Furthermore the observed multipotency of adult Mesenchymal Stem Cells (MSCs) including their ability to differentiate into cells found in the adult heart, such as cardiomyocytes and endothelial cells, sparked interest to develop them for future cell-based therapy such as heart valve engineering. MSCs are commonly isolated from the bone marrow and represent a great cell source for tissue engineering of living heart valves mainly due to their wide availability [14,16,20,21]. However, adult bone marrow derived MSCs are suboptimal for clinical use due to the required highly invasive donation procedure and the decline in both their proliferation and differentiation potential with increasing senescence.…”

Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric Aortic Valve Interstitial Cells within 3D Engineered Matrices

“…[12][13][14] Among various MSC sources, bone marrow-derived MSC (BMMSC) and adiposederived MSC (ADMSC) are prime candidates for TEHV due to their greater availability and popularity. [15][16][17][18][19] However, a few studies have compared phenotype and extracellular matrix (ECM) deposition characteristics between MSC and VIC, especially pediatric VIC. VIC are a heterogeneous population of quiescent fibroblasts, a small population (*20% for neonatal, *6% for child and *2.5% for adult valves) of myofibroblasts and mesenchymal progenitor cells.…”