Umbilical cord-derived Wharton’s jelly for regenerative medicine applications

Abstract

Background: The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton's Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton's jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes. Methods: Human umbilical cords were obtained from consenting caesarian section donors. The Wharton's jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles. Results: All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-α, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Proinflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles. Conclusion: There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton's jelly formulation analyzed. The amount of these factors in Wharton's jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.

Umbilical cord: an allogenic tissue for potential treatment of COVID-19

“…The UC is a neonatal tissue composed of two arteries and a vein supported within connective tissue referred to as WJ, it connects the developing fetus and the placenta allowing the fetus to receive nutrient rich oxygenated blood from the placenta [79]. WJ is a mucoid connective tissue between the amniotic epithelium and the umbilical vessels within the UC, and provides protection, cushion, and structural support to the umbilical vessels [19]. The UC can be obtained without having a patient undergo an invasive procedure, unlike sources like DP, BM, and adipose tissue.…”

“…UC-MSCs can be easily and quickly expanded, due to their doubling times, to reach the numbers needed to have a clinically efficacious treatment [81]. WJ is rich with MSCs, GFs, CKs, and EVs especially compared to other sources, with the highest concentration of MSCs per milliliter than any other allogenic tissue [19,82]. UC-MSCs have been shown to be significant regulators of activated T cells contributing to their superb ability for immunosuppression and regulation of the innate and adaptive immune responses.…”

“…WJ is a connective tissue located within the UC known to resist compressive and torsional forces during fetal development. WJ contains high levels of primitive MSCs with the highest concentration of MSCs per milliliter than any other allogenic tissue [ 19 ]. WJ-MSCs have also been shown to be mostly multipotent rather than pluripotent and secrete large quantities of anti-inflammatory cytokines (CKs), growth factors (GFs) and extracellular vesicles (EVs) including exosomes compared to other sources [ 18 , 20 , 21 ].…”

­Evaluation of Immediate and Short-Term Efficacy of DualStim Therapy with and without Intracavernosal Umbilical Cord-Derived Wharton’s Jelly in Patients with Erectile Dysfunction: Study Protocol for a Pilot Randomised Controlled Trial

“…Its key role is to provide cushion, protection and structural support to umbilical vessels by avoiding their bending, torsion and/or compression (38). Our recently published study reported presence of numerous growth factors, cytokines, hyaluronic acid and extracellular vesicles including exosomes in the WJ, and the amount of these factors was higher compared to other biologics (36). WJ is also known to contain high amounts of extracellular components such as collagen and sulfated proteoglycans (39).…”

“…WJ offers many advantages over most other biologic options. The expansion properties of umbilical-derived stem cells and clinically signi cant amounts of regenerative substances and its ease of harvest make it a promising biologic source (36,37).…”