Fibrin, the preferred scaffold for cell transplantation after myocardial infarction? An old molecule with a new life

Abstract

Fibrin is a topical haemostat, sealant and tissue glue, which consists of concentrated fibrinogen and thrombin. It has broad medical and research uses. Recently, several studies have shown that engineered patches comprising mixtures of biological or synthetic materials and progenitor cells showed therapeutic promise for regenerating damaged tissues. In that context, fibrin maintains cell adherence at the site of injury, where cells are required for tissue repair, and offers a nurturing environment that protects implanted cells without interfering with their expected benefit. Here we review the past, present and future uses of fibrin, with a focus on its use as a scaffold material for cardiac repair. Fibrin patches filled with regenerative cells can be placed over the scarring myocardium; this methodology avoids many of the drawbacks of conventional cell-infusion systems. Advantages of using fibrin also include extraction from the patient's blood, an easy readjustment and implantation procedure, increase in viability and early proliferation of delivered cells, and benefits even with the patch alone. In line with this, we discuss the numerous preclinical studies that have used fibrin-cell patches, the practical issues inherent in their generation, and the necessary process of scaling-up from animal models to patients. In the light of the data presented, fibrin stands out as a valuable biomaterial for delivering cells to damaged tissue and for promoting beneficial effects. However, before the fibrin scaffold can be translated from bench to bedside, many issues must be explored further, including suboptimal survival and limited migration of the implanted cells to underlying ischaemic myocardium. Copyright © 2016 John Wiley & Sons, Ltd.

p38α MAPK inhibition translates to cell cycle re-entry of neonatal rat ventricular cardiomyocytes and de novo nestin expression in response to thrombin and after apex resection

“…In the present study, successful ventricular apex resection of 1-day old neonatal rat hearts was confirmed by the appearance of minute bleeding immediately after surgery leading to the formation of a fibrin clot sealing the exposed chamber. The latter paradigm may further represent an essential prerequisite biological event initiating a cardiac regenerative response as fibrin is an important natural scaffold providing the necessary matrix for cell migration, adhesion and proliferation 35 . Morphologically, fibrin clot formation after apex resection was associated with a significant reduction of left ventricular free wall thickness and septal wall thickness in vehicle-treated apex-resected heart as compared to neonatal sham hearts.…”

Hemostasis mechanism and applications of N-alkylated chitosan sponge

“…The largest effort has come from the United States Army in their evaluation of sprayable fibrin foams for use in truncal bleeding . However, results with the fibrin sprays have been equivocal, and fibrin use in the field is limited due to its cost, storage requirements, and preparation before application . Other products, such as thrombin‐based hemostatic agents, lyophilized platelets, conjugated red blood cells (RBCs), and fibrinogen‐coated albumin microparticles also have limitations for practical applications …”

Mesenchymal stem cells for cardiac repair: are the actors ready for the clinical scenario?

“…For instance, although direct contact with neonatal rat cardiomyocytes could effectively induce a cardiomyocyte-like phenotype in cATMSCs [ 22 ], it did not promote the expression of cardiomyocyte-specific proteins, rhythmic calcium oscillations, or potential-dependent fluorescence emissions in these cells [ 34 ]. In the following, we also describe how UCBMSC-embedded fibrin patches could not effectively induce cardiac-specific markers, such as cTnI, in MI hearts [ 36 , 37 ].…”

“…Other in-vivo experiences have included the use of alginate, hyaluronic acid, gelatin, and matrigel (revised in [ 51 ]). Alternatively, our group has evaluated the implantation of fibrin as a scaffold material for cardiac repair (revised in [ 37 ]). Thus, we generated 3D engineered fibrin patches filled with cATMSCs or UCBMSCs and delivered them to postinfarcted myocardium in mice [ 36 , 40 , 52 ].…”