New Frontiers in Regenerative Medicine in Cardiology: The Potential of Wharton’s Jelly Mesenchymal Stem Cells

Abstract

Cardiomyopathies are still the first cause of death in the world. The identification of resident stem cells, comprising those derived from sub-endocardial stroma, suggests the possible self regeneration of the heart under autocrine/paracrine modulation in the cardiac microenvironment. Nevertheless, because of the limited in vivo regeneration potential of damaged cardiac tissue, the use of drugs and ultimately cardiac transplantation remain the common treatments of heart diseases and defects. The differentiative potential of embryonic and mesenchymal stem cells (MSCs) derived from different tissues (such as bone marrow and adipose tissue) was extensively explored in cell therapy for regenerative medicine. Many groups have been focused, in recent years, on isolation, characterization, and differentiation potential of MSCs derived from perinatal (or extraembryonic) tissues, mainly the placenta and the human umbilical cord. In this review, we summarized recent works about the stemness of Wharton's jelly stromal cells and their potential in cardiac regeneration with favourable use in cell therapy and regenerative medicine. The peculiar features of these cells, as the expression of cardiac-specific transcription factors and immunomodulatory molecules suggest that human umbilical cord may be considered as a reliable alternative source of MSC useful for advanced therapy in cardiac regenerative medicine.

Apelin: an endogenous peptide essential for cardiomyogenic differentiation of mesenchymal stem cells via activating extracellular signal‐regulated kinase 1/2 and 5

“…It has been demonstrated that WJ-MSCs have greater expansion capability, faster growth in vitro, and more multipotent differentiation capacity (Wu et al, 2007;Chen et al, 2009;Ishige et al, 2009). In addition, WJ-MSCs suppress immune rejection and curb the inflammatory response in allotransplantation (Wu et al, 2007;Semenov and Breymann, 2011;Corrao et al, 2013;Kim et al, 2013). With these advantages, WJ-MSCs have been used in cardiomyogenic regeneration and cardiovascular tissue engineering (Kadner et al, 2002;Semenov and Breymann, 2011;Corrao et al, 2013;Kim et al, 2013;NCT01291329).…”

Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms

“…In this study, a specific population of human stem cells derived from the umbilical cord tissue (Wharton’s jelly), hereafter designated UCX®, was isolated, expanded, and cryopreserved on the basis of proprietary technology developed within our team [43]. We show that UCX® delivery into the myocardium of mice subjected to left anterior descending (LAD) coronary artery ligation (a) preserves heart function, (b) attenuates the cardiac remodeling process, (c) increases capillary density, and (d) prevents apoptosis in the infarcted tissue.…”

Regenerative potential of Wharton's jelly‐derived mesenchymal stem cells: A new horizon of stem cell therapy

“…Phenotypic investigation performed by several groups evidenced that WJ‐MSCs fit the minimal criteria for MSCs as proposed by the International Society for Cellular Therapy (Dominici et al, 2006). They are spindle‐shaped fibroblast‐like cells expressing typical mesenchymal markers such as CD73, CD90, CD105, CD13, CD29, and CD44, while lacking expression of hematopoietic, CD45, CD34, and endothelial, CD31, markers (Corrao et al, 2013; Kalaszczynska & Ferdyn, 2015). WJ‐MSCs can also be unique options for therapeutic applications due to their primitive properties, as they display several characteristics of embryonic stem cells (ESCs), such as ESC‐like antigen Tra‐1‐60, Tra‐1‐81, SSEA‐1, and SSEA‐4, and pluripotency genes including Oct‐4, Nanog, SSEA‐4, and SOX‐2 (Marino et al, 2019).…”