Is the secret in the stem cell secretome?

Major breakthroughs in stem cell research have not yet proven clinical success — all live adult stem cell therapies, bar hematopoietic stem cell transplantations, remain experimental.

steps from harvesting fats cells to various therapeutic uses

Our primitive understanding of both the mechanisms of such therapies and the pathologies of the diseases they treat is today's therapeutic reality and why all stem cell therapies beyond HSCT are experimental.

It has been 20 years since the promise that stem cell therapy will revolutionize the practice of medicine.

Today every major city has dozens of MD offices and chiropractic clinics offering unproven and downright fraudulent Stem Cell therapies. For the most part people are being helped with these overpriced and unproven therapies, but we don’t know precisely why. The autologous cell theory is valid (use your own cells to heal yourself) but it is a shame doctors must forge forward blindly because there is no agreement as to what works, and if not, why? It is more of a shame that allogeneic “stem-cell-like” therapies — using tissue harvested from other people (cord blood, omentum, amniotic fluid, etc,) or from animals are growing into big business selling products with no live stem cells in them. That is fraud, in my opinion, but I am glad it is not illegal because like I said, for the most part, it works. We just don’t know precisely why it works after billions of dollars of research from every major university. Like most health care practices, it suffices not-to-know how or why, as long as we do no harm. People need these therapies now and screw the FDA; a theory is good enough for me. The well-characterized curative effect of transplanted mesenchymal stem cells has been mainly attributed to their homing and subsequent differentiation for the repair and regeneration of damaged tissue. Liposuction stem cells have immense potential, however, there is a pre-requisite to develop a curative cell dose. Adipose tissue-derived mesenchymal stem cells are promising mainly due to their potential abundance, immunomodulatory effect, and remarkable differentiation potential.

Hematol Transfus Cell Ther. 2019 Jan-Mar;41(1):7–16

but it is complicated…

The epigenetic memory of either bone marrow or adipose stem cells causes the tendency to grow into bone or fat cells respectively. But these cells work remarkably well in dozens of non- blood, bone or fat, diseases causing obvious regeneration and repair.

Still the methylation status of adult stem cells you harvest limits their ability to change into stem cells of your target tissue.

Mixing stems cells from different parts of your body will alter the treatment efficacy depending on the ratio of those mixtures.

Designing minimally manipulated stem cell treatment regimens for individuals by adjusting the cell ratio before the treatment is just as promising as using the FDA yet-unapproved pharmacological manipulation of adult stem cells.

Clin Transl Med. 2018 Feb 7;7(1):5.

Pharmacological manipulation for purification and expansion by culture, prior to clinical use, works well but is still considered experimental. Also, using flow cytometry machines to purify fat cells into optimal stem cell ratios is also experimental “Manipulation”. Applying stress stimuli such as low pH and physical pressure on stem cells- reported to induce pluripotency is also experimental manipulation.

The big problem with the manipulation of your cells before injecting them back into your body for therapy is senescence. Time after harvesting fat or bone marrow cells greatly affects in vivo potency of the stem cell cultures but also might be the source of clinical inconsistency arising from infused cell preparations.

Gaur M Methods Mol Biol. 2019 Mar 6.

So today there is a little we can legally do to our own cells without using all those manipulation techniques (which cost taxpayers billions of dollars to discover, but we must wait till it is proven profitable for big pharma before we can use). Just harvesting from more than one body part may increase the potency of stem cell target differentiation. Also, the regenerative benefit of live stem cells may be irrelevant to much of what is now being sold as “stem cell” therapy. Though I believe it fraudulent to advertise stem cell therapy anything that is not from your own body and injected back in the same day, those fraudulently named therapies are helping lots of people.

Those off-the-shelf remedies work for many reasons besides live stem cells or placebo effect. Those therapeutic outcomes are achieved possibly via autocrine and paracrine effects of the dead stem cell secretome comprising of cytokines, extracellular proteins, and RNAs. Therefore, secretome-derivatives might offer huge advantages over cells through their synthesis and storage for long-term use.

Int J Mol Sci. 2018 Jul 27;19(8)

This is contrary to the historic hypothesis that stem cell migration and transdifferentiation is the primary mechanism-of-effect of stem cell injection therapies.

“Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration?”. Cellular and Molecular Life Sciences. 70 (20): 3871–3882.2013

logo for secretome without borders conference

Though live cell therapy has been shown to be relatively safe, from a clinical standpoint, the use of cell-free infusions can altogether circumvent the administration of viable cells for therapy.

The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine.

graphic of factors secreted by stem cells like growth factors, cytokines, exosomes…

Cytokine Growth Factor Rev. 2019 Apr;46:1–9

Of course, bottling the stem cell secretome will lead to “pharmaceuticalization” and we can forget that promise that stem cell therapy will revolutionize the practice of medicine away from drugs to self-healing.

Freeze-dried and GMP-compliant pharmaceuticals containing exosomes for acellular mesenchymal stromal cell immunomodulant therapy.

Nanomedicine (Lond). 2019 Mar;14(6):753–765.