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Panacea of 21st century for ovarian rejuvenation

7 December 2020
By Dr Dusko Ilic
Assisted Conception Unit, Guy's Hospital, London
Appeared in BioNews 1075

In ancient times, theriac, a medical concoction made by Greeks that was thought to cure all illnesses, had spread all over the then known world. It took months to prepare a proper theriac and that, of course, made it expensive. Only rich people could afford it. The recipe for theriac kept changing over time, depending on the availability of ingredients. In medieval times, it included ground mummy. In the Venetian Republic, in addition to viper flesh and opium, it included exudate from the castor sacs of mature beavers. Today, the theriac recipe has lost its magic and mystique. Nearly all ingredients are chemically defined, along with their specific applications. For example, beaver castoreum has 24 compounds, mostly ketones, phenols and alcohols. We use it mostly in the perfume industry, while Swedes use castoreum to flavour their Bäverhojt schnapps.

The theriac of old may have been explained away; but does have a modern equivalent. Today, theriac is called mesenchymal stem cells (MSC). MSCs can cure almost anything, we are told. Just name it: osteoarthritis, COVID-19, autism, and infertility. Before all of you who struggle with fertility rush to your nearest purveyor of this new miracle treatment, take a moment to read here what we actually know about MSCs, how they work, and what they can do. If you then still believe that they are the solution to your problems, go for it (Madonna fixed her knee cartilage with stem cells, did she not?). Good luck to you. If you change your mind, you'll be saving several thousands of pounds, that might be better spent on your Christmas shopping.

MSCs are adult stem cells traditionally found in the bone marrow, but are also found in multiple tissues of the body. These cells are multipotent; they can differentiate only into cells types originating from the same germ layer, contributing to the lymphatic, circulatory or musculoskeletal systems. If you delve into the scientific literature, you will find reports claiming that scientists have been able to transdifferentiate MSCs into cells of ectodermal and endodermal tissues, just because they were able to detect one or two of these cell lineage markers. However, their presence alone is insufficient evidence. 

MSCs have gained popularity for several reasons: 1) They had no specific markers, and nobody could prove whether the cells are indeed MSCs or not; 2) conservative forces, fighting the use of human embryonic stem cell (hESC) for research and therapy, bestowed power on MSCs with little or no evidence at all. With no ethical strings attached, MSCs were presented as being as biologically powerful as hESCs. The Vatican was even organising MSC-related stem cell conferences; and 3) they can be easily isolated from bone marrow or adipose tissue and re-injected back into the same person in a different site, circumventing any legal or medical issues attached to transferring biological material between patients as long as the procedure was done at the required safety standards with no apparent intent to harm (intentional harm of a patient's bank account might be considered an acceptable exception). 

After years of fiddling with MSCs and trying to understand what they can do and how they work, it seems that the idea that stem cells could differentiate and be used to replace damaged tissue did not work as we expected. When injected into a human, their life is short, and engraftment is generally low; most of the MSCs end up stuck in the capillary network of the lungs. Some of them find a home in damaged tissue. Numerous studies have shown that MSCs can modulate the progression of inflammation and maintenance of tissue homeostasis via an array of immunosuppressive factors, cytokines, growth factors and differentiation factors. MSCs are recruited to the site of inflammation and there, in response to inflammatory cytokines, they suppress the activation and function of various cells of the innate and adaptive immune systems via a different mechanism.

Their remarkable immunomodulatory properties are used in the treatment of severe systemic inflammatory disorders such as steroid-resistant acute graft-versus-host disease. What do these immunomodulatory properties have to do with fertility? How will they rejuvenate ovaries and revive the menstrual cycle? 

For me, it is very difficult, if not impossible, to connect all the knowledge about MSCs with their application in fertility treatments. I am a stem cell scientist and I have worked with stem cells for more than 20 years. I have strong evidence-based reasons to argue that any stem cell therapy currently offered for fertility treatment would not work beyond a placebo effect.

I am also sure that many of you will have a different opinion.

14 May 2018 - by Paul Waldron 
The US Food and Drug Administration is seeking to shut down two clinics offering treatments based on stem cells...
20 November 2017 - by Dr Patrick Foong 
Stem cell research holds tremendous promise for the treatment of a wide variety of illnesses and conditions, from spinal cord injury to autism. However, much more work is necessary to translate stem cell research into safe and effective therapies...
9 October 2017 - by Jen Willows 
The reputation of stem cell research is being undermined by unscrupulous clinics offering unproven therapies, says a report published last week...
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