Concise Review: Wharton's Jelly: The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells

Abstract

The umbilical cord has become an increasingly used source of mesenchymal stromal cells for preclinical and, more recently, clinical studies. Despite the increased activity, several aspects of this cell population have been under‐appreciated. Key issues are that consensus on the anatomical structures within the cord is lacking, and potentially different populations are identified as arising from a single source. To help address these points, we propose a histologically based nomenclature for cord structures and provide an analysis of their developmental origins and composition. Methods of cell isolation from Wharton's jelly are discussed and the immunophenotypic and clonal characteristics of the cells are evaluated. The perivascular origin of the cells is also addressed. Finally, clinical trials with umbilical cord cells are briefly reviewed. Interpreting the outcomes of the many clinical studies that have been undertaken with mesenchymal stromal cells from different tissue sources has been challenging, for many reasons. It is, therefore, particularly important that as umbilical cord cells are increasingly deployed therapeutically, we strive to better understand the derivation and functional characteristics of the cells from this important tissue source. Stem Cells Translational Medicine 2017;6:1620–1630

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

“…A recent comprehensive report on the proteome and transcriptome profiles of MSCs revealed source specific markers [37]. In addition, differences that exist in CFU-F efficiency, surfactome profiles, multilineage differentiation as well as paracrine functions [35,36,[38][39][40][41] may determine their different clinical applications.…”

Overview of methods of isolation, cultivation and genetic profiling on human umbilical cord stem cells

“…The umbilical arteries and vein differ in structure from regular vessels of similar diameter. They comprise tunica intima and tunica media but they lack tunica adventitia [11]. The wall of the umbilical cord vein consists of a thick layer of circular, longitudinal and oblique smooth muscle fibers and internal elastic lamina, whereas the arteries are devoid of internal and external elastic lamina [10].…”

“…Tunica adventitia is considered to support vasculature and exhibit contractile function, however in the umbilical cord its role is thought to be fulfilled by Wharton's jelly [12]. It also prevents the vessels from kinking and it provides them with insulation and protection [11,13]. Wharton's jelly is an embryonic gelatinous connective tissue containing amorphous ground substance and connective tissue cells [14].…”

“…Wharton's jelly is an embryonic gelatinous connective tissue containing amorphous ground substance and connective tissue cells [14]. The extracellular matrix comprises collagen (predominantly type I), proteoglycans, such as hyaluronic acid and diffusible plasma proteins [11]. MSCs comprised in the Wharton's jelly resemble fibroblasts.…”

“…However, they also contain myofilaments and express desmin and vimentin, therefore they have been called 'myofibroblasts' [15]. Since the Wharton's jelly has no nervous or vascular elements (except for the three umbilical vessels), it is unique among other connective tissues [11].…”