Imaging cardiac extracellular matrices: a blueprint for regeneration

Abstract

Once damaged, cardiac tissue does not readily repair and is therefore a primary target of regenerative therapies. One regenerative approach is the development of scaffolds that functionally mimic the cardiac extracellular matrix (ECM) to deliver stem cells or cardiac precursor populations to the heart. Technological advances in micro/nanotechnology, stem cell biology, biomaterials and tissue decellularization have propelled this promising approach forward. Surprisingly, technological advances in optical imaging methods have not been fully utilized in the field of cardiac regeneration. Here, we describe and provide examples to demonstrate how advanced imaging techniques could revolutionize how ECM-mimicking cardiac tissues are informed and evaluated.

Spatial and Temporal Analysis of Extracellular Matrix Proteins in the Developing Murine Heart: A Blueprint for Regeneration

“…39 Of these, the most prevalent, functionally relevant ECM proteins in the developing heart include (1) COLI and COLIII, fibrillar proteins that provide structural support, 19 (2) COLIV and other basement membrane proteins that serve to align and polarize cell layers, 36,40 (3) FN, which attaches to cell surface integrins and other ECM proteins (including COLI, fibrin, heparin, and syndecan) to mediate changes in the structural or mechanical properties of the matrix and phenotype of adhering cells, 41,42 and (4) elastin (ELN), which is critical for elasticity, allowing tissue to stretch and recoil, as in the beating heart. A summary of ECM protein expression and distribution in the embryonic mouse and chick hearts was recently reviewed by Jung et al 43 The reviewed studies identify general changes in ECM protein expression and distribution, which likely contribute to important changes in cell behavior, such as proliferation, which is most active between embryonic day (E) 11.5-14, 44 and terminal differentiation of cardiac cells, which is most active between E8.5-E13.5. 45 Despite the breadth of studies examining the ECM composition during cardiac development, we failed to find any study that directly established a blueprint of essential ECM proteins and quantified changes in relative amount and distribution at different embryonic developmental stages.…”

Decellularized scaffolds as a platform for bioengineered organs

“…Furthermore, the use of multiphoton microscopy combined with image correlation spectroscopy has been proposed as a noninvasive method to predict the mechanical properties of decellularized heart tissue [25]. Other imaging techniques, such as transmission electron microscopy, cryo-electron tomography and atomic force microscopy are gaining attention in the evaluation of cardiac ECM [26]. …”

Nano-imaging collagen by atomic force, near-field and nonlinear microscope

“…Collagen is the main component of connective tissues in mammals, present in the majority of extracellular tissue with mechanical functions 1 . In humans, for example, collagen makes up most of the proteins forming tendons, ligaments, bones, blood vessels etc.…”