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Learning to speak to secretomes

biomarker gifThe secretome is a cell free fluid that concentrates the therapeutic components produced by stem cells, giving them healing powers.  The secretome can be produced from a healthy  person or one’s own cells.  The starting material can come from several sources, blood cells or fat cells are favored. The secretome is thought to give stem cells their effectiveness in various diseases.

The secretome is a collection of “paracrine” soluble factors produced by stem cells that are used for inter-cell communications. The paracrine factors also assist in tissue development, regulate normal functions, and regenerate damaged tissues.  Secretomes can inhibit some cancers. The factors are contained in extracellular vesicles and micro vesicles as well as unbound membrane particles, short bits of proteins (peptides) and cytokines.

These are important factors in degenerative, auto-immune and inflammatory diseases. That makes the secretome relevant to many therapeutic uses that include arthritis, chronic lung disease, multiple sclerosis, cancer, and stroke. Secretome is generally considered safe in humans and animals and is in several clinical trials in the United States. In 2017, a preparation of secretome was deployed in Russia for eye and skin injuries in animals.  Not available in the US, you can order Penapuh drops from an online Russian company.  Check out the 4,087 scientific papers on secretomes to really appreciate this expanding field.

One paper referred to cross-talk between the body’s stem cells and the central nervous system (CNS).  If we could decipher this chatter, we would direct CNS healing in diseases that currently have no treatment! The secretome has piqued our interest for both amyotrophic lateral sclerosis (ALS) and equine neurodegenerative disease.  We have gathered 10 research laboratories across the US, each with unique expertise, into one group,to find hope for ALS patients  Sixty-percent of our efforts use stem cell science to understand disease and how to crack the secretome language. We are holding the pedal to the metal as we explore how to get an effective therapy into desperate people and beloved horses.

wbcstem cellThe illustrations are of white blood cells in the peripheral circulation and a picture of stem cells in the flask after processing.  The stem cells are assayed for several specific markers.  And then they are expanded and some are frozen.  A research step for us is determining if starting cells, the factories to produce the secretome, should come from a healthy person or from a patient already afflicted with a disease. Are cells that have been in a diseased environment primed to respond to a curative mode? Or are cells from healthy sources more capable of sending healing messages to tissues? We have two laboratories asking that one question. The consensus opinion of the group is that a healthy cell should be the starting material.

The next unknown is the cell phenotype produced from the undifferentiated cell and how to appropriately induce the cells to communicate with the diseased body.  Stem cells are induced to produce one cell type. In disease, there are multicellular communications that are disturbed between hundreds of other differentiated cell types.  The source of tissue and cell type that are induced are key issues that must be addressed with firm scientific basis. When cells age in the laboratory, they change their secretome.  What’s old in a flask can simply mean 10 or 15 doublings. The change is a change in their phenotype.  If it takes a long time to get enough cells in the flask, their phenotype won’t be the same as the starting cell. You can already envision the changes if autologous cultures are used in some diseases, autologous means the individual donates the cells. There are obvious advantages to a specific cell background that are modified to an individual disease or unique disease process. However, once we can break the language code, we can tell the cells what we’d like them to say.

These are all issues for licensing the ultimate product for the patient.  The goal is a unified line that can become a licensed therapeutic that is safe and effective for the condition that is treated.  That means a safety study (with a price of half a million dollars for horses and more in humans).  Sometimes, if there is literature to support safety and toxicity, time and money are saved.  A dose must be determined from clinical trials.  That dose is used in a toxicity study that is mandated by regulatory agencies.  Rodent toxicity studies are about a quarter of a million dollars.  The dose titration is done by treating patients within a safety study.  If all goes well, the dose is escalated in a second or even a third trial.  Time and money.

To initiate a clinical trial the product is manufactured.  Before clinical trials are contemplated, one must have an idea of the dose, duration, and frequency of treatment.  That will have a direct effect on the formulation, and formulation studies are expensive. The next decision is packaging.  The ultimate package is cast in stone once the initial exploratory batches are used in trials.  Should it be a liquid, lyophilized, or a tablet? That is determined by the expected stability of the product.  Secretome that is liquid in a vial would need refrigeration or freezing, but consider the longevity (stability) of the final product if it was lyophilized!  When dosing a laboratory animal, a vial with a therapeutic volume of 0.1cc is great, but when scaled up to a human, or horse, one would want to avoid 20 mouse vials for one treatment!  And a horse might require 10 times the human volume, 200 mouse-vials.  Lyophilization can overcome that obstacle. All these steps total close to five million dollars…or more.

phone boothFormula and packaging are set. Manufacturing is complete.  Off to regulatory officials to decide on the best path to get into trials.  Phenotype selection is based on cell culture conditions that were worked out when we learned to speak their language. We give them the messages so they can don their superhero costumes and churn out the paracrine factors that are expected to ameliorate disease.  This is what we are working on.  If you’d like to participate, please use the following link. And keep an eye out for our progress, we will report it here. Click here to donate.