Wharton's jelly-derived cells are a primitive stromal cell population

Abstract

Here, the literature was reviewed to evaluate whether a population of mesenchymal stromal cells derived from Wharton's jelly cells (WJCs) is a primitive stromal population. A clear case can be made for WJCs as a stromal population since they display the characteristics of MSCs as defined by the International Society for Cellular Therapy; for example, they grow as adherent cells with mesenchymal morphology, they are self-renewing, they express cell surface markers displayed by MSCs, and they may be differentiated into bone, cartilage, adipose, muscle, and neural cells. Like other stromal cells, WJCs support the expansion of other stem cells, such as hematopoietic stem cells, are well-tolerated by the immune system, and they have the ability to home to tumors. In contrast to bone marrow MSCs, WJCs have greater expansion capability, faster growth in vitro, and may synthesize different cytokines. WJCs are therapeutic in several different pre-clinical animal models of human disease such as neurodegenerative disease, cancer, heart disease, etc. The preclinical work suggests that the WJCs are therapeutic via trophic rescue and immune modulation. In summary, WJCs meet the definition of MSCs. Since WJCs expand faster and to a greater extent than adult-derived MSCs, these findings suggest that WJCs are a primitive stromal cell population with therapeutic potential. Further work is needed to determine whether WJCs engraft long-term and display self-renewal and multipotency in vivo and, as such, demonstrate whether Wharton's jelly cells are a true stem cell population.

Conflict of interest statement

Disclosure of Potential Conflicts of Interest

M. Weiss has acted as a consultant to Regenerative Medicine Institute (Las Vegas, NV), Nacelle Therapeutics (Manhattan, KS), and KPL (Rockville, MD); has performed contract work for Toucan Capital II (Bethesda, MD) and Nacelle Therapeutics; and has a financial interest in Regenerative Medicine Institute.

Figures

Figure 1

Compartments within the umbilical cord. Five separate regions have been shown to contain mesenchymal stromal cells: (1) MSCs can be isolated from 20–50% of freshly prepared mononuclear cell fractions from umbilical cord blood; (2) MSCs have been isolated from umbilical vein subendothelial layer; (3) MSCs can be isolated following enzymatic digestion of the outer layers of umbilical vessels, for example, the perivascular region; (4) intravascular space consistently produces MSCs in healthy individuals; (5) the subamnion region. Wharton’s jelly includes zones 3 through 5. This review focuses on Wharton’s jelly-derived cells and not on MSCs derived from umbilical cord blood (zone 1) or umbilical vein subendothelium (zone 2).

Figure 2

Venn diagram illustrating common and differing properties between adult mesenchymal stromal cells (MSCs; gray oval) and Wharton’s jelly-derived cells (WJCs, umbilical cord matrix cells; yellow oval). Adult MSCs are defined by International Society for Cellular Therapy working group as cells that are plastic adherent, possess specific surface markers, and are capable of differentiating into multiple mesenchymal lineages, (e.g., bone, cartilage, muscle, tendon, adipose, etc.). As indicated by the overlap, the WJCs share these properties. Similarly, as discussed within, stromal support, specific immune properties of low immunogenicity and immune suppression, and the ability to migrate to pathology are taken to be properties of adult MSCs. These properties are observed in WJCs. Also indicated, adult MSCs have limited expansion capability in vitro before their multipotency is compromised. In contrast, Wharton’s jelly cells can be expanded >15 passages. WJCs, like MSCs from other sources, can serve as feeders for embryonic-like stem cells and for hematopoietic stem cells. In contrast to adult MSCs, WJCs may be derived from extra-embryonic tissue; this may explain why those cells express human leukocyte antigen-G (HLA-G) isoform and glial derived neurotrophic factor (GDNF). Abbreviation: ???, unknown.