Profiling extra cellular matrix associated proteome of human fetal nucleus pulposus in search for regenerative targets

Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the core matrisome of fetal NP’s and identified various proteins with anabolic potential for regenerative therapies. This study aims to complement those results by exploring ECM regulators, associated proteins and secreted factors of the fetal nucleus pulposus (NP). Proteomic data of 9 fetal, 7 healthy adults (age 22–79), and 11 degenerated NP’s was analyzed. Based on the selection criteria, a total of 45 proteins were identified, of which 14 were uniquely expressed or upregulated in fetus compared to adult NP’s. Pathway analysis with these proteins revealed a significant upregulation of one pathway and two biological processes, in which 12 proteins were involved. Prolyl 4 hydroxylase (P4HA) 1 and 2, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) 1, and Heat shock protein 47 (SERPINH1) were involved in ‘collagen biosynthesis’ pathway. In addition, PLOD 1, SERPINH1, Annexin A1 and A4, CD109 and Galectin 3 (LGALS3) were all involved in biological process of ‘tissue development’. Furthermore Annexin A1, A4 and A5, LGALS-3 and SERPINF1 were featured in ‘negative regulation of cell death’. In conclusion, additionally to core ECM proteome, this study reveals ECM regulators and ECM affiliated proteins of interest to study for regenerative therapies, and their potential should be validated in future mechanistic experiments.

A Brief History in Cardiac Regeneration, and How the Extra Cellular Matrix May Turn the Tide

Tissue homeostasis is perturbed by stressful events, which can lead to organ dysfunction and failure. This is particularly true for the heart, where injury resulting from myocardial infarction or ischemic heart disease can result in a cascading event ultimately ending with the loss of functional myocardial tissue and heart failure. To help reverse this loss of healthy contractile tissue, researchers have spent decades in the hopes of characterizing a cell source capable of regenerating the injured heart. Unfortunately, these strategies have proven to be ineffective. With the goal of truly understanding cardiac regeneration, researchers have focused on the innate regenerative abilities of zebrafish and neonatal mammals. This has led to the realization that although cells play an important role in the repair of the diseased myocardium, inducing cardiac regeneration may instead lie in the composition of the extra cellular milieu, specifically the extra cellular matrix. In this review we will briefly summarize the current knowledge regarding cell sources used for cardiac regenerative approaches, since these have been extensively reviewed elsewhere. More importantly, by revisiting innate cardiac regeneration observed in zebrafish and neonatal mammals, we will stress the importance the extra cellular matrix has on reactivating this potential in the adult myocardium. Finally, we will address how we can harness the ability of the extra cellular matrix to guide cardiac repair thereby setting the stage of next generation regenerative strategies.

A NUMERICAL PROOF THAT CERTAIN CELLS FOLLOW THE TRAILS OF THE DIFFUSIONS OF SOME CHEMICALS IN THE EXTRACELLULAR MATRIX

In this work, we obtain the numerical solutions of a 2D mathematical model of tumor angiogenesis originally presented in [Pamuk S, ÇAY İ, Sazci A, A 2D mathematical model for tumor angiogenesis: The roles of certain cells in the extra cellular matrix, Math Biosci 306:32–48, 2018] to numerically prove that the certain cells, the endothelials (EC), pericytes (PC) and macrophages (MC) follow the trails of the diffusions of some chemicals in the extracellular matrix (ECM) which is, in fact, inhomogeneous. This leads to branching, the sprouting of a new neovessel from an existing vessel. Therefore, anastomosis occurs between these sprouts. In our figures we do see these branching and anastomosis, which show the fact that the cells diffuse according to the structure of the ECM. As a result, one sees that our results are in good agreement with the biological facts about the movements of certain cells in the Matrix.