THE SECRET OF SUCCESS IN CELL THERAPY

1- A Universal Medicine
We're accustomed to using different medications to treat various diseases, and it's sometimes difficult to understand that the same medication is used to treat completely different conditions. This is because the action of MMSCs is not directed at the disease itself, but at restoring the body's ability to regenerate and fight disease. Like vitamins, MMSCs act throughout the body, helping it cope with disease and restore lost functions.

2 - Diagnosis and Treatment
Multipotent mesenchymal stromal cells (MMSCs) have unique properties, one of the most important of which is pathotropism—their ability to independently find sites of damage and inflammation in the body, attach to them, and initiate "repair." This pathotropism is based on the fact that any pathological site in the body produces proteins that trigger damage or inflammation, and MMSCs have receptors for these proteins. Like a predator following a scent, MMSCs "catch" these proteins in the body and latch onto damaged sites. Thus, MMSCs not only provide treatment but also diagnosis, independently detecting diseases that may remain undetected by tests and symptoms.

3 - Holistic Approach
The cells act on the entire body, restoring its functions and circulation, activating defense and regeneration.

4 - Natural Mechanism
Cell therapy is a natural treatment method based on natural, genetically programmed mechanisms.

Allogeneic (donor) multipotent mesenchymal stromal cells (Al-MMSCs) from bone marrow

We use MMSCs derived from the bone marrow of young, healthy donors for therapy. Compared to the patient's own (autologous) cells, donor cells have a significantly more pronounced therapeutic and revitalizing effect.

All donors are healthy young adults aged 18-25. Dokar independently selects donors. Donors must not smoke, drink alcohol, or use drugs. They must not have tattoos (tattoos significantly reduce the activity of MMSCs).

Before bone marrow collection, donors undergo a full physical examination. Bone marrow is collected from the iliac crest in a quantity of no more than 100 ml. The procedure is performed under local anesthesia (ultracaine) and is painless. The donor feels well.
Pure cells (MMSCs) are isolated from the bone marrow and tested for safety and activity. Then the pure fraction of MMSC is placed in a nutrient medium and grown under certain conditions (temperature, pressure, lighting, O2 and CO2 concentration) for 5-7 days.

Bone marrow
Bone marrow (BM) is the only human tissue containing a large number of regenerative cells. Bone marrow is a reserve supply of stromal cells for natural regeneration and emergency recovery (during injuries or acute illnesses). There are two types of cells in bone marrow:

• Hematopoietic cells (HPCs) – can transform into blood cells (erythrocytes, leukocytes, and platelets)
• Mesenchymal multipotent cells (stromal cells, MMSCs) – can transform into most cell types.

Key properties of bone marrow MMSCs:

1. Regeneration. Bone marrow performs all regeneration in the body. This mechanism is created by nature.
2. Regulation and control. Bone marrow mesenchymal cells control the activity of hematopoietic and local progenitor cells. If necessary, they can activate and transform into them.
3. Multipotency is the ability to transform into virtually all cells in the body.
4. Maturity. Mesenchymal stromal cells are adult, resistant cells. Unlike embryonic and umbilical cord stem cells, they are completely safe.

Age and regeneration

As a result of natural aging, disease, degeneration, and injury, the number and activity of BM-MMSCs (bone marrow mesenchymal stromal stem cells) decreases, and the body's ability to self-renew is impaired. By age 50, the number of MMSCs decreases by 20 times, and by age 75 to 100 times.
In addition to the decrease in quantity, the activity and mobility of MMSCs also significantly decrease with age.

Therapeutic properties of MMSC

Pathotropism is the ability to independently detect sites of inflammation and cell death in the body and repair damaged areas. When cells die and become damaged, special protein molecules (damage markers) are produced. MMSCs capture these markers and travel through the bloodstream to the affected areas.

Paracrine effect – the ability to produce over 100 biologically active substances in four directions:

Cytokines – activate the body's own local progenitor cells, which form new cells to replace damaged ones.
Regeneration activators – growth factors, antifibrotic and antiapoptotic substances, peptides, external matrix molecules, etc.
Immunomodulators – reduce inflammation and balance the interaction of the immune system with the body's own tissues.
Angioprotectors – stimulate microcirculation and form new capillaries.

MMSC - differences between donor (allogenic) MMSC and one's own (autologous):

1. Donor MMSCs are more active because they are obtained from younger and completely healthy donors.

2. Donor MMSCs have a long-lasting paracrine effect (the ability to activate the body's own local progenitor cells and produce growth factors). The body's own MMSCs do not have this effect – they immediately transform into specialized cells to replace damaged ones.

3. Limited duration of action – donor MMSCs are active for 30 days, after which apoptosis (MMSC death) occurs, and their remnants are utilized by the body's own leukocytes.

MSC is safe and compatible

Compatibility - Donor MMSCs do not react with the patient's immune system, so they can be administered to any patient. This is due to the presence of a special protein on the surface of MMSCs, MHC-1. There are no reported cases of immune incompatibility with donor MMSCs during their therapeutic use.

Is there a risk of rejection?

Donor (allogeneic) mesenchymal multipotent stromal cells (MMSCs) do not react with the immune system and, therefore, do not pose a risk of allergic reactions or rejection.

MMSCs possess one important property: the ability to actively interact with and modify the activity of virtually all cells of the immune system (IS), creating an immunotolerant environment for both the MMSCs themselves and surrounding cells and tissues.

Their immunomodulatory properties allow MMSCs to be considered a safe means of overcoming pathological inflammatory processes and ensuring immune tolerance during organ transplantation and autoimmune diseases. MMSCs are capable of influencing immune system cells both directly and indirectly (through other immune cells). MMSCs exert their immunomodulatory effects through various mechanisms, including the secretion of soluble factors and cell-cell interactions with target cells.

Safety. MMSCs are unable to proliferate or transform in the body. They have only a paracrine effect – they produce growth factors, signaling molecules, etc., which reduce inflammation and activate regeneration. The use of this type of stem cell began in 1996, and as of 2020, no adverse events have been reported.

Is there a risk of cancer?

In 2013, a group of European scientists published a long-term safety study of MMSC infusion procedures used to treat orthopedic conditions. Between 1990 and 2006, 1,873 patients were treated with bone marrow-derived MMSCs. Patients were followed from the time of their first injection in 1990 until December 31, 2011, or the earliest date of death. This long period (an average of 12.5 years, ranging from 5 to 22 years) helped monitor the potential development of cancer. The primary outcome was to assess the risk of tumor development at sites treated with MMSCs. A secondary outcome was to assess the risk of cancer diagnosis at sites not treated with the cells. After reviewing 7,306 MRI images and 52,430 X-rays from 1,873 patients, not a single tumor was detected at sites treated with MMSCs.

The study showed no increased risk of cancer development over a mean follow-up period of 12.5 years.

There is no rational reason for this fear, other than that of an entirely different cell type (embryonic stem cell), which, although named the same (stem cell), can cause teratomas – hence the confusion!