Secretome and exosomes are sometimes used as synonyms, but they are actually different.

The secretome is the totality of all messenger substances released to the outside, including the micro-vesicles and exosomes, but also other important factors that are dissolved in the fluid. These include many regeneration-promoting growth factors and so-called cytokines (cell-cell messengers).

Exosomes, on the other hand, are actually only the particulate exosomes that are isolated from the whole. Isolation concentrates them, but the important solutes and micro-vesicles are lost.

In short, compared to BMC, pure mesenchymal stem cells are obtained and several doses can be obtained from one tissue collection, which makes it particularly suitable for the treatment of chronic diseases.

Moreover, the secretome is storable, fully quality controlled before use and is made from 90-98% pure MSC mesenchymal stem cells.

The use of stem cells is still limited in most countries. This has severely limited their use in medicine despite their presumed and in some cases clinically proven efficacy in treating many chronic or incurable diseases. Reasons for this include the fact that stem cells can lose their efficacy if they expand too much, altered cells can develop, and stem cells, at least those derived from blood (hematopoietic stem cells), are altered when frozen, which in turn alters their potential efficacy, including the composition of the substances they deliver to the outside world.

This may now be changing, with one of the latest breakthroughs in stem cell research: the ANOVA science team has developed and implemented a process that extracts and concentrates the components of stem cells that are evidence-based to be therapeutically active - the stem cell secretome.

The secretome that ANOVA uses in Offenbach provides safety in several respects.

No living cells are injected into the patient, i.e. no altered stem cells can be injected.

The secretome is made of mildly expanded (i.e. potentially less altered cells). Thus, the composition is the natural one, which is not altered by freezing.

After production, the secretome can be stored in this composition. Exosomes and other substances contained in the secretome remain stable. This allows to produce numerous doses with one withdrawal, which can then be used for more than 2 years.

Thus, treatment with secretome is the better option especially for chronic diseases.

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Step 1 - Harvesting Mesenchymal Stem Cells (MSCs) from subcutaneous adipose tissue

At ANOVA we use the so-called "nutational infrasonic liposuction", employing the Euromi Lipomatic® system. This procedure provides 10 to 100 times more viable MSCs obtained from the harvested adipose tissue than any other technique.

The adipose tissue is immediately processed in an ISO and GMP-certified clean-room guaranteeing the highest possible quality and safety of the end product.

Step 3 - Application and treatment with ANOVA's Stem Cell Secretome therapy

From a single isolation of stem cells via liposuction of the patient's adipose tissue (step 1), up to 10 therapeutic doses of Stem Cell Secretome can be obtained that are to be administered systemically via infusion.

The earliest application of Stem Cell Secretome is possible 4 weeks after liposuction. During that time, our specialists in the laboratory prepare the product and perform quality controls.

The scheme below summarizes all steps towards your individual therapy at ANOVA IRM. It starts from your first charge-free contacts and inquiries to ANOVA including the initial analysis whether our therapies are suitable for treatment of your condition and if you are eligible as a donor. Continues with financial issues such as cost-estimate and treatment contracts, virtual or in person doctoral appointments, your trip to Offenbach, Germany, testing, physical exams, tissue donation, stem cell product cultivation and quality control up to application.

More Information on exosomes is also given in your blog post: The Power of Exosomes.

Vocabulary and Definitions

Differentiation - Stem cells have the potential to differentiate into different cell types depending on external stimuli and signals. MSC e.g. must be able to become at least bone cells, cartilage cells and fat cells to be called stem cell.

Cancer, cancer cell - cells in which the normal regulation of cell division is no longer functional. These cells divide even though this would not be necessary and thus continue to multiply to the detriment of the organism.

Morphology - The shape, appearance of cells under the microscope.

Proliferation - cell division, cell multiplication

Stem cell - a cell that has a greater potential in its reproduction than normal body cells. It can renew itself and differentiate into several cell types = functionalize.

What is a Secretome?

Stem cells communicate with other cells by releasing messenger substances to the outside. The totality of all released substances is called secretome (from secretion = release to the outside). The secretome can contain exosomes, micro-vesicles, proteins, growth factors, hormones, cytokines and other substances. A scientific review article on vesicles can be found here.

What is an Exosome?

Exosomes are small messenger packages that cells release to the outside.They ar a part of the secretome.

Exosomes are approximately 30-100nm (i.e. 0.03 to 0.1mm) in size and consist of an outer double-lipid layer (like liposomes) and an interior that can be loaded with fluid and messengers such as miRNA and proteins. Exosomes are released to the outside by the fusion of multi-vesicular corpuscles inside the cell with the cell membrane. There, they can be taken up by other cells to mediate reactions. A scientific review article on vesicles can be found here.

What are Micro-Vesicles?

Micro-vesicles are also lipid membrane-coated particles that can carry cargo. However, at 100 to 1,000nm in size, they are larger than exosomes and are released to the outside by pinching off (exocytosis) at the cell membrane. A scientific review article on vesicles can be found at hier.

What are Growth Factors?

Chemically, growth factors usually are proteins that bind to receptors on the outer surface of target cells. Many cells produce growth factors such as EGF (epidermal growth factor), PDGF (platelet-derived growth factor), NGF (neuronal growth factor), bFGF (basic fibroblast growth factor) etc. Growth factors in general are not related to Human growth hormone (HGH).

Cells respond to their environment. They divide only when necessary. In a healthy body, for example, a liver cell divides only once a year to replace dead cells. The signal for a cell to divide can be the loss of neighboring cells (cut) or growth factors produced by other cells. These factors diffuse to other cells, bind to receptors on the surface, and trigger signaling cascades inside the target cell that stimulate division. Inflammation often inhibits cell division (proliferation).

How is Secretome Produced? What Tissue is Used for Secretome Production?

The secretome used by the ANOVA Institute for Regenerative Medicine is produced from mesenchymal stem cells of the patient (autologous = own stem cells). These are extracted from the abdominal fat in a short, mini-liposuction and subsequently cultivated very gently and thus propagated.

After fat harvesting, the starting material is the SVF (stromal vascular fraction) isolated from it, which contains only about 1-10% MSC and progenitor cells. Subsequently, the MSC are cultivated, multiplied and a pure culture consisting of 90-98% MSC is obtained.

The fact that these cells are division-active stem cells has been proven by a so-called multi-differentiation assay. In this, the MSC are differentiated into cell types (cartilage cells, bone cells and fat cells) over 2-3 weeks. If this is successful, we have one of several proofs that the cells are indeed stem cells. In addition, we check each batch for purity.

What are the Advantages of Secretome?

The great advantage of the secretome is that it can be frozen. If stem cells are frozen, their properties change and this can lead to a loss of efficacy. In the case of chronic diseases, however, a continuous therapy is needed, i.e. stem cells would have to be taken again and again. In the case of secretome, one can obtain 10-20 doses from one collection and thus treat repeatedly over a period of 2 years.

Another advantage is that MSC (mesenchymal stem cells, stromal cells), which are cultivated over a longer period of time, bear the risk of cancer cells developing in the culture. If these cells are then used, they will be transferred to the patient. This risk does not exist with the ANOVA secretome, as it is cell-free and tested.

More Stem Cells - More Effect? Older Stem Cells - Lower Efficacy!

Many patients believe that a larger amount of stem cells also achieves better effects. This is correct up to a limit that is difficult to define. However, since it is not yet possible to measure "efficacy", or only in very few cases, one should be very cautious here. Many characteristics of stem cells are not well understood so far and nobody knows exactly which factors and substances define an effect. The only thing that is really known exactly is that with increasing multiplication (generations, population doublings) the efficacy potential decreases. That is, the more you multiply stem cells, the less likely they are to still be effective.

ANOVA therefore multiplies the cells only within very conservative limits internationally recognized by research and science, so that the risk of potential loss of efficacy is kept extremely low.