What is Wharton’s jelly & its possible clinical uses?

For more than a year in my first job as a scientist I isolated cells from umbilical cord veins and then tossed the tissue away, never realizing there was more there that could be useful in the form of something called Wharton’s jelly.

What’s in this article

Umbilical cord histology & Wharton’s jelly | What is Wharton’s jelly? | Cells & other substances in Wharton’s jelly | Clinical trials | Fact-checking claims | FDA considerations and data | References

The goal of today’s post is to teach you all the basics and some more advanced information about this unusual material. A second objective is to fact-check some of the clinical claims out there.

Umbilical cord histology & Wharton’s jelly

Fortunately, I teach histology as a professor here at UC Davis School of Medicine and we cover the umbilical cord. So I have some knowledge of the anatomy and histology of the cord.

Wharton's jelly umbilical cord H&E
An H&E stained section of umbilical cord. Different key features including the area where the Wharton’s jelly is isolated from are highlighted. The Wharton’s jelly is much of the material around the vein and arteries. The Niche.

Wharton’s jelly is a unique substance found in the wall of the umbilical cord surrounding the blood vessels. Its precise location is not well-defined in most cases. If you look at the annotated image I made above you can get a sense that the jelly is like a ring surrounding the vessels. Usually it is just isolated in bulk. Some research suggests that isolating more specific layers of the stroma of the umbilical cord  via precision dissection may give different forms of jelly with distinct properties.

Wharton’s jelly  contains mesenchymal stromal cells (MSCs) along with other cells and potentially useful substances. The potential therapeutic properties of this jelly are being explored in a variety of clinical trials.

Wharton's Jelly, umbilical cord clinical trials
Umbilical Cord Cell Clinical Trials Data Showing the Range of Diseases Being Examined. Stem Cells Translational Medicine 2017.

What is Wharton’s jelly?

While the blood inside of the umbilical cord has gotten the most attention in this area, the wall of the cord turns out to be quite interesting as well. Within the cord blood there are hematopoietic stem cells (HSCs) and other immune cells.

The umbilical cord wall also contains MSCs and a variety of other similar cells. Once the cord blood is removed if it is to be banked, usually the cord is then discarded. As I said earlier, the same is often true for lab research on endothelial cells. However, in some cases material from the wall of the cord is isolated. It is this gelatinous substance that is Wharton’s jelly.

Mucopolysaccharides give it its jello-like nature and the jello-like nature of this substance gives the “jelly” to the name. Type I collagen is also abundant.

The moniker “Wharton” comes from an English anatomist named Thomas Wharton, who first reported on it. The best biography of Thomas Wharton that I could find was on Wikipedia, which got it from a centuries-old dictionary.

Cells & other substances in Wharton’s jelly

Jelly cells

There are several types of cells in this tissue including MSCs, fibroblasts (what’s the difference between a fibroblast and an MSC?), blood vessel cells including pericytes, and immune cells. If a lab makes a stromal cell prep from Wharton’s then they will have this heterogeneous product. Product heterogeneity is a real challenge in this area. It’s possible that only a subset of these cells are useful and others could even be actively unhelpful. Davies, et al. report that only 1 out of 300 cells in Wharton’s jelly is actually an MSC.

Growth factors

There is also a vast array of growth factors and other substances in this jelly. Their identities and properties have been studied quite a lot, but are not that well understood in terms of therapeutic properties attributable to specific factors or combinations.

Still, data to date suggest some useful activities here.

Clinical trials

I found 49 trials mentioning Wharton’s jelly on Clinicaltrials.gov in a recent search. The diseases listed in these trials are very diverse ranging from arthritis to nephropathy to erectile dysfunction to COVID-19 to paralysis. And many more. A similar broad range of disease focuses was presented in a graph in a recent paper (see screenshot above).

Zero out of the 49 listings had data in the listing, which makes it difficult to evaluate their potential.

Interestingly, Europe has the most clinical trials by far (see map below).

Wharton's Jelly, umbilical cord clinical trial map
Wharton’s Jelly clinical trial map. Screenshot from Clinicaltrials.gov.

Fact-checking claims

Despite this jelly having real potential, many are getting carried away about it. Some stem cell clinics are already selling injections of material. Even some academics are getting ahead of the data in terms of how they discuss it. In short, it’s being hyped sometimes.

In terms of the clinics, I had an easy time finding many selling it via a Google search for a wide range of conditions.

I think it’s likely that in the next 10 years one or two specific clinical applications will be proven safe and effective. However, it is not a panacea or magic jelly.

FDA considerations and data

The FDA has issued a variety of untitled and warning letters in this space. While I don’t recall seeing formal guidance on Wharton’s jelly, it’s safe to say that in many cases it is going to be a drug product. This is especially the case if there are living cells being injected into patients. Since the umbilical cord is the baby’s tissue, unless any material from it was used to treat that very same baby, the material will be allogeneic. The FDA did include this jelly in a recent advisory it issued on June 3,2021:

“The US Food and Drug Administration (FDA) regulates regenerative medicine products. There continues to be broad marketing of unapproved products considered regenerative medicine therapies that are intended for the treatment or cure of a wide range of diseases or medical conditions. These products require FDA licensure/approval to be marketed to consumers. Before approval, these products require FDA oversight in a clinical trial. These unapproved products whether recovered from your own body or another person’s body, include stem cells, stromal vascular fraction (fat-derived cells), umbilical cord blood and/or cord blood stem cells1, amniotic fluid, Wharton’s jelly, ortho-biologics, and exosomes. FDA has received reports of blindness, tumor formation, infections, and more, detailed below, due to the use of these unapproved products.”

I found more than 650 PubMed articles with Wharton’s jelly as the title words. The vast majority were on MSCs. Eleven of the papers were on clinical trials. Could this help us get data since no data is listed on Clinicaltrials.gov?

Yes and no.

There were a few rigorous trials and a few signs of possible efficacy, but overall I’d say the potential here remains unclear. It’ll be interesting to follow the research and clinical trials in this space moving forward.

References

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