A Combined Synthetic-Fibrin Scaffold Supports Growth and Cardiomyogenic Commitment of Human Placental Derived Stem Cells

Abstract

AimsA potential therapy for myocardial infarction is to deliver isolated stem cells to the infarcted site. A key issue with this therapy is to have at one's disposal a suitable cell delivery system which, besides being able to support cell proliferation and differentiation, may also provide handling and elastic properties which do not affect cardiac contractile function. In this study an elastic scaffold, obtained combining a poly(ether)urethane-polydimethylsiloxane (PEtU-PDMS) semi-interpenetrating polymeric network (s-IPN) with fibrin, was used as a substrate for in vitro studies of human amniotic mesenchymal stromal cells (hAMSC) growth and differentiation.Methodology/Principal FindingsAfter hAMSC seeding on the fibrin side of the scaffold, cell metabolic activity and proliferation were evaluated by WST-1 and bromodeoxyuridine assays. Morphological changes and mRNAs expression for cardiac differentiation markers in the hAMSCs were examined using immunofluorescence and RT-PCR analysis. The beginning of cardiomyogenic commitment of hAMSCs grown on the scaffold was induced, for the first time in this cell population, by a nitric oxide (NO) treatment. Following NO treatment hAMSCs show morphological changes, an increase of the messenger cardiac differentiation markers [troponin I (TnI) and NK2 transcription factor related locus 5 (Nkx2.5)] and a modulation of the endothelial markers [vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR)].Conclusions/SignificanceThe results of this study suggest that the s-IPN PEtU-PDMS/fibrin combined scaffold allows a better proliferation and metabolic activity of hAMSCs cultured up to 14 days, compared to the ones grown on plastic dishes. In addition, the combined scaffold sustains the beginning of hAMSCs differentiation process towards a cardiomyogenic lineage.

A Nanostructured Bacterial Bioscaffold for The Sustained Bottom-Up Delivery of Protein Drugs

“…In addition, scaffolds loaded with releasable growth factors, again targeting regeneration, are under continuous development. In this context, polyurethane-fibrin complexes [43], electrospun fibers loaded with growth factor-encoding expressible DNA [44], TGF-b-loaded fibrin scaffolds [45], PDGF-loaded electrospun PLGA/PEG-PLA composite [46] and FGF-1-loaded PEGDA hydrogels [47] are a few recent examples among the wide spectrum illustrating these approaches.…”

Early gestation chorionic villi-derived stromal cells for fetal tissue engineering

“…Placenta-derived mesenchymal stromal cells (PMSCs) are analogous to the MSCs routinely obtained from bone marrow in both surface marker expression and multipotency [20,21] . Investigators interested in utilizing PMSCs or other fetal-derived mesenchymal stromal cells have demonstrated their potential for engineering bone [22][23][24] , cartilage [25][26][27] , and muscle [28][29][30] , as well as pancreatic [31] , neural [7,17] and cardiac tissues [18,[32][33][34] . The gestational age of the source tissue may affect the therapeutic capabilities of the cells.…”

Cells, Scaffolds and Their Interactions in Myocardial Tissue Regeneration

“…Hence, biosimulation of cardiac microenvironment into the scaffolds is an important matter to determine the output of heart tissue engineering. Specifically, all of the cardiac microenvironment components including growth factors [Lin et al, ; Lisi et al, ], decellularized tissue matrices [Xu et al, ] and synthetic polymer scaffolds [Parrag et al, ; Crowder et al, ] are as key matters to achieve the effective injured heart masculinization and revascularization. Moreover, preserving the survival and function of the seeded cell against the low oxygen and nutrient condition [Kawamura et al, ] is a crucial feature for heart tissue engineering efficiency which it has a close relationship with biosimulation of the cardiac microenvironment.…”

“…It has been shown that interaction of cells with scaffold components through promoting the various signaling pathways can control the cells survival as well as stem cells proliferation, differentiation, and also formation of functional tissue [Kaiser and Coulombe, ]. Currently, the combination of several growth factors with scaffolds such as VEGF, b‐FGF, PDGFBB [Lin et al, ; Lisi et al, ; Matsuda et al, ] and IGF‐1 [Karam et al, ] is known to be an appropriate method for regulating the engineered tissue microenvironment and also for controlling the survival of the cells, and their differentiation. Different cardiac ECM proteins like Gsn, Vdac2, and Hspa1l are reported as the significant cellular regulators which inhibit the cell death and control the actin filaments assembly and disassembly [Sun et al, ; Baraniak and McDevitt, ].…”