Abstract
BACKGROUND: Wharton’s jelly, the mucoid connective tissue that surrounds umbilical cord vessels, contains both acellular and cellular components with recognized relevance to regenerative medicine. The acellular extracellular matrix (ECM) is composed of collagen fibers, hyaluronic acid, proteoglycans, glycosaminoglycans, that provides a scaffold for bioactive molecules such as growth factors and cytokines that support structural integrity and tissue repair. The cellular component of native Wharton’s jelly consists primarily of multipotent mesenchymal stromal cells (MSCs), which are leveraged in regenerative medicine for their differentiation capacity, trophic signaling, angiogenic activity, and immune modulatory activities. There is a growing commercial market for injectable, minimally manipulated Wharton’s jelly allograft products for clinical use to provide structural support or cushioning. Although these products comprise ECM, they are often presumed or represented to also contain viable MSCs capable of providing therapeutic benefit. METHODS: A comprehensive literature review was performed, examining published data on the biologic components of Wharton’s jelly and common methods of processing and utilizing this tissue as a source of ECM or MSC-based therapeutics. Empirical laboratory analyses were also conducted on minimally manipulated Wharton’s jelly tissue products to microscopically quantify total cell content, viable cell counts, and to assess the percentages of MSCs by flow cytometry. RESULTS: Published literature shows that ECM-based preparations can support endogenous repair processes or serve as scaffolds in tissue engineering, but they do not contain therapeutically meaningful quantities of viable primary MSCs. To achieve any measurable biological or clinical effect using MSCs, administration of MSCs at defined therapeutic doses is required, typically ≥10 million MSCs for local delivery and 70–190 million cells for systemic infusion. These doses can only be obtained by intentionally isolating MSCs from fresh Wharton’s jelly tissue and subsequently expanding them in vitro. Indeed, our analyses of minimally manipulated Wharton’s jelly product samples show that these materials contain ECM with only trace levels of residual cells. Total cell counts in Wharton’s jelly tissue preparations ranged from 3,369 to 111,170 cells per cubic centimeter, with 0–19.1% viability, and only rare viable MSCs. CONCLUSIONS: Minimally manipulated Wharton’s jelly products should be viewed as acellular ECM preparations, comprising negligible MSCs and lacking the capacity to provide cell-mediated therapeutic benefits. An understanding of the compositions of ECM products and true MSC-based therapies is essential to ensure appropriate clinical use and responsible integration into regenerative medicine practices.