Postinfarction Functional Recovery Driven by a Three-Dimensional Engineered Fibrin Patch Composed of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells

Abstract

Considerable research has been dedicated to restoring myocardial cell slippage and limiting ventricular remodeling after myocardial infarction (MI). We examined the ability of a three-dimensional (3D) engineered fibrin patch filled with human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) to induce recovery of cardiac function after MI. The UCBMSCs were modified to coexpress luciferase and fluorescent protein reporters, mixed with fibrin, and applied as an adhesive, viable construct (fibrin-cell patch) over the infarcted myocardium in mice (MI-UCBMSC group). The patch adhered well to the heart. Noninvasive bioluminescence imaging demonstrated early proliferation and differentiation of UCBMSCs within the construct in the postinfarct mice in the MI-UCBMSC group. The implanted cells also participated in the formation of new, functional microvasculature that connected the fibrin-cell patch to both the subjacent myocardial tissue and the host circulatory system. As revealed by echocardiography, the left ventricular ejection fraction and fractional shortening at sacrifice were improved in MI-UCBMSC mice and were markedly reduced in mice treated with fibrin alone and untreated postinfarction controls. In conclusion, a 3D engineered fibrin patch composed of UCBMSCs attenuated infarct-derived cardiac dysfunction when transplanted locally over a myocardial wound. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:956-966 SIGNIFICANCEIschemic heart failure (HF) is the end stage of many cardiovascular diseases, including myocardial infarction. The only definitive treatment for HF is cardiac transplant, which is hampered by limited number of heart donors and graft rejection. In recent times, cellular cardiomyoplasty has been expected to repair infarcted myocardium by implantation of different sources of stem or progenitor cells. However, low cell survival and myocardial implantation rates have motivated the emergence of novel approaches with the objective of generating graftable cell-based implants. Here, the potential of 3D engineered fibrin-umbilical cord blood-derived mesenchymal stem cells patches is shown to significantly recover lost general functions in post-infarcted mice.

Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine

“…In this context, due to their regenerative and immunomodulatory capacities, mesenchymal stem cells (MSCs) have been proposed as powerful inhibitors to counteract such unwanted immune responses. Thus, MSCs represent a promising strategy for a variety of medical conditions, including treatment of damaged tissue, inflammatory diseases and transplantation 1,2.…”

Electrical and mechanical stimulation of cardiac cells and tissue constructs

“…In addition, when using cell types such as skeletal myoblasts, poor electrical integration into the host tissue can lead to secondary complications such as arrhythmias [19]. The use of tissue-engineered grafts has also shown significant promise in small animal models [20–24], but concerns about cell/ graft viability and the level of cell maturity have limited the clinical potential of tissue-engineered grafts. Future success and development of cardiomyoplasty- and cardiac graft-based treatment strategies would benefit from optimized in vitro methods to evaluate cardiomyocyte (CM) viability, phenotype, maturation level, and contractility under varying conditions that mimic the in vivo cellular environment.…”

Characterization of Sox9‐overexpressing human umbilical cord blood‐derived mesenchymal stem cells‐based engineered cartilage both in vitro and in vivo

“…Similar to the MSCs from other tissues, hUCMSCs can give rise to different cell types including bone, cartilage, adipose tissue, cartilage, and neuron . Preclinical studies have revealed that transplantation of an engineered fibrin patch composed of hUCMSCs can improve cardiac function after myocardial infarction and the implanted cells contribute to the formation of new, functional microvasculature . Another study reported that transplantation of chitosan scaffolds seeded with hUCMSCs facilitates brain tissue regeneration in a rat model .…”