Just one word placentas: Can Celularity live up to hype?

I’ve been blogging about stem cells now for about 8 years and the recent level of hype about and fluffy media coverage of Celularity, the biotech Celularity Logospun out of Celgene, ranks right up here with the most extreme past cases I’ve seen.

What is Celularity and who is its leadership?

It’s a new biotech focused on placental stem cells with some familiar, well-known leaders including Bob Hariri and Peter Diamandis, and famous tech names on their board including John Scully and Bill Maris, along with past FDA Commissioner Andrew Von Eschenbach. And this company expresses some big aspirations via stem cells.

  • Extend human life by decades.
  • Fight cancer through CAR-T cells.
  • Treat Crohn’s disease.
  • And much more.

And this all will be achieved through the apparent unprecedented power of one particular kind of cells: placental stem cells.

You can see a screenshot below of just some of the media coverage popping up on Google News.

Celularity

The statements by Celularity’s leadership are not just ambitious in terms of the types of conditions and diseases to tackle, but also the short target timeline to take them to patients. For example, FierceBiotech has this surprising quote:

“Hariri said that the company “anticipates rolling treatments out through partner clinics within the next four years,” although he says that timeline “may change” as it collects more data.”

Just four years? That would seem to necessitate not getting an IND from the FDA or going through the clinical trials process.

What exactly are these partner “clinics”?

To my knowledge, placental stem cells are going to require an IND (wouldn’t their isolation from placenta likely be a drug manufacturing process? And the cells are going to be used in an allogeneic manner by definition, their uses are almost always going to be non-homologous, etc.) so how can they start selling them through clinics in just a few years? I hope that particular plan, should it materialize, won’t be like the stem cell clinics out there that transplant cells into patients without FDA approvals.

Overall, could the company be at risk of overselling placental stem cells? This other quote from the FierceBiotech piece might suggest so:

“When asked what evidence the company had that a placenta-based therapy could work, Hariri responded: “The placenta is the most powerful resource known to medicine.”

By chance, I happen to help teach about placenta in our med school histology course so I know a fair amount about it. Placenta is a cool tissue and somewhat unexplored territory relative to other organs. It has some unique immune properties as well. In addition, Hariri also has quite a few interesting research articles (note that a few of these articles on PubMed may be by someone else with a similar name) on placenta and other related materials. However, placenta is the most powerful resource known to medicine? Why?

This placenta buzz related to Celularity reminds me of the famous scene in the movie The Graduate where the older guy gives the young man played by Dustin Hoffman advice about the future “Just one word: Plastics.” (see clip below) But here with Celularity and its media coverage, the quote would be “Just one word: Placentas!”

Unfortunately, FierceBiotech’s piece misses the boat on some of the science here with statements like this, which isn’t a quote from Celularity, but is just stated as fact:

“Unlike embryonic stem cells, placental cells are incredibly pure, meaning they can be taken from any placenta and injected into any human without the risk of the body rejecting them.”

What is meant here by “pure”?

Unlikely to trigger an immune response?

To me as a stem cell biologist this seems like an odd word to use in that context. Purity would refer properly to homogeneity. Also, getting back to the immunity idea, it is debatable at best to make a blanket statement that placental stem cells have no risk of rejection in any human into which they are injected. That’s very unlikely to be the case so broadly.

Practically speaking, it turns out that Celularity not only has $250 million in capital, but also owns the stem cell bank firm, LifeBankUSA, which apparently can generate millions in profits to serve as fuel for Celularity’s many other efforts. This gives them a leg up on many otherwise similar stem cell biotechs.

Notably, some of the media coverage of Celularity has been more balanced including this piece by Matthew Herper, which appropriately ends this way:

“Those are big promises. At the least, it won’t be boring.”

We’ll have to see how things turn out, but the overall hype here has raised expectations so sky-high that they’re going to be difficult if not impossible for Celularity to meet. As Herper said, at least it won’t be boring to watch Celularity’s efforts.

5 thoughts on “Just one word placentas: Can Celularity live up to hype?”

  1. Academic skeptic

    I agree with Jeanne’s interest in the placenta, and Paul’s skepticism about Celularity. I do not know much about Bob Hariri, but just attended the Perinatal Stem Cell meeting in Salt Lake City where Bob gave a talk. Although he is a slick speaker with fancy slides, there was very little substance or data to support any claims or provide more specific information as to exactly what they’re doing and how they plan to do it. He did mention his private jet, though, so I guess there’s that.

  2. Hi Paul- there might still be some people out there who remember my Embryology lab course at UC Davis in the 1980s. I was intrigued by extraembryonic membranes and structures- the amnion, the chorion, the yolk sac – that were extensions of the ectoderm, mesoderm, and endoderm that gave rise to the fetus.

    Warning: I’m really interested in placentas, so this will be a long post.

    I brought in a placenta to each lab section every quarter and showed the students how it worked to connect the baby to the mother. Babies bust through the amnionic membrane when they’re born, remaining connected to the placenta only by the umbilical cord, that has the same layers.

    The placenta is a mixture of maternal and fetal blood vessels, where exchange of nutrients and wastes happens. It works for the purpose of supporting a fetus to term…but would it be good for anything else? This is unknown.

    Dissociating the placenta would yield mesenchyme from the fetus, mixed with maternal and fetal endothelial cells. The only advantage of placenta mesenchyme might have over other sources of mesenchymal cells is that they express HLA-G instead of HLA-A, B, and C. If the fetal cells in the placenta made HLA-A, B, and C, the fetus would be rejected as foreign because half the HLA molecules would come from the father. HLA-G engages the mother’s immune system as the other HLAs do, but HLA-G does not activate T cells or NK cells, the major monitors of foreign and abnormal tissues.

    T cells cause attack of foreign cells, and NK cells are responsible for monitoring abnormal cells, such as cancers. Without NK cells to take out early cancerous cells, we would all die young from cancer.

    Is HLA-G a good thing? It makes cells invisible to the host immune system, so they won’t be attacked by NK or T cells.

    Fetal mesenchymal (FM) cells are not stem cells- they are not used to replace cartilage, bone, or fat, since those are not components of the placenta. Would FM last longer in the body than MSCs after transplantation? Probably. But is that a good thing? Are these cells more prone to making cancers because they are invisible?
    Completely unknown.

    So it’s not just one word: “Placenta”. It’s “HLA-G”, “T-cells”, “NK cells”, and “Fetal Mesenchyme”. There may be a situation in which it is desirable to have mesenchyme survive wherever it’s injected, but I can’t think of one.

  3. Paul, UCB is FDA approved for allogeneic hematopoeitic reconstitution. There are thousands of USB transplants every year, most are allogeneic. Hariri has patents around perfusion of placenta (so do I) for collection of stem cells using perfusion. It is similar to “milking” the cord and provides advantages and it gives you cord blood mixed with isotonic saline, which is essentially the same to what you’d get after purifying the TNC fraction from a UCB unit. And keep in mind that the UCB dose approved is Total Nucleated Cell population, generally characterized by viability, CD34 content, infectious diseases, etc. – so any attempt to isolate a “pure” strain of cells (like MSC) or to market for any non-hematopoeitic use would be more trhan minimally-manipulated and would require and IND, NDA application. I suspect they intend to supply “UCB-like” preparations to physicians from placenta for “off label” use, which can be a non-compliant practice (FDA has been famously tough on many Big Pharma companies for doing this)- these articles rasied the Red Flag to me that if marketed for this purpose (and if this isn’t marketing I don’t know what is), it is illegal. So I agree that the hype is too much, but I do share their enthusiasm for use of placental cells over bone marrow aspirate from some old guy like me.

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