What factors determine the treatment effect of MSC (Part One)

The clinical research of MSC has been carried out for many years, but various treatment results have been obtained. Why so? What kind of factors affect the results?  Here in this article, we summarized several possible reasons based on study results and clinical practice.

Mesenchymal stem cells (MSCs) are one of the stars in clinical applications. There have been many reports of mesenchymal stem cells trying to treat a variety of diseases. It can be used to “treat” a variety of diseases, but it does not mean that MSC is the best or only choice for these diseases, nor does it mean that MSC can cure these diseases. It can only be said that researchers have tried MSC to treat these diseases. And some get pretty good results.

There are many factors that affect the efficacy of MSC. This article mainly focus on cell quality, injection route, optimal dose, and timing of treatment. Of course there are other factors, such as the type of disease, the course of the disease, the medical technology implemented by the doctor, and the overall strength of the hospital.

  1. Cell quality

There are some differences in the quality of the same drug produced by different manufacturers. The same situation exists for different stem cell companies.

Let’s first define what is “cell quality”?

Cell quality refers to the biological potency of a unit cell or a single cell; the higher the potency, the better the cell quality.

Efficacy includes two factors, strength and effectiveness, that is, the effect achieved at the same strength (generally refers to concentration). Therefore, when we talk about efficacy, we should be specific. The concept of efficacy is widely used in the biological world, including pesticides and drugs. This concept is also applied to the field of stem cells.

Therefore, when we talk about the cell quality or biological efficacy of MSC, specific indications are specific. We should talk about how effective this is in a range of indications. For example, MSC has both the function of immunosuppression and the promotion of vascular regeneration, and two different types of diseases are treated separately, then there are two indicators of biological efficacy.

However, the basic and clinical research of MSC has not yet entered this subdivided field. Here we will talk about the cell quality and what factors are relevant.

There are some parameters that can reflect the quality of mesenchymal stem cells, such as cell viability, donor characteristics, clone formation ability, cell size, immunosuppressive ability, and cytokine secretion. Here is a brief introduction to cell viability and donor characteristics.

  1. A. Cell viability

It refers to the alive number of MSCs before MSC injection. It is rare in the literature to explicitly mention the cell viability of MSCs. The cell viability used in different clinical studies is different, including > 80%,> 85%, 88.2 ± 6.1%, 90% -97%,> 92%,> 95%. There are also cases > 70%.

Cell preparations with a viability of 90% or more and with only 70% have a large difference in treatment effect under the same disease conditions. After all, MSC needs to be alive, and it needs to be cleared from the lungs in order to play a good therapeutic role. So, cell viability is really important!

  1. Donor characteristics

Donor characteristics include “donor age” and “donor physical condition”.

(1) Donor age

Donor age is an important factor because MSCs from young donors appear to have greater viability, proliferation potential, and antioxidant capacity, while older adult-sourced MSCs have lower proliferation capacity. In terms of age, umbilical cord, umbilical cord blood, and placenta should have the most advantages, followed by deciduous teeth and pulp, while bone marrow and fat are relatively older.

The older the age, the fewer stem cells are in the bone marrow. At birth, 1 of the 10,000 mononuclear cells in the bone marrow is MSC. At 30 years of age, the number of MSCs is reduced to 250,000 mononuclear cells in the bone marrow. By the age of 80, the number of MSCs will be even smaller, and only 2,000,000 MSCs will have one MSC.

Gender may affect some functions of the MSC. For example, studies have shown that female-derived MSCs express higher levels of IFN-γR1 and IL-6β, and thus have stronger immunosuppressive capabilities.

So what are the functional differences between MSCs from different sources? MSCs from different tissues have certain differences, which are mainly reflected in the proliferation rate, secreted cytokine profile, and immunoregulatory ability of MSCs.

(2) Physical condition of the donor

Many studies have proved that the disease also affects the function of autologous mesenchymal stem cells, especially in some patients with autoimmune diseases, the MSCs of their own bone marrow have abnormal functions, including slower proliferation rate, reduced colony formation ability, and decreased immune suppression changes, such as the decrease in the amount of secreted growth factors, make the patient’s own bone marrow MSCs unsuitable for the treatment of their own diseases.

Theoretically, there may be some kind of congenital genetic mutation that causes the function of MSC to be defective, so MSCs derived from umbilical cord, cord blood, and placenta at the time of birth are not suitable for autologous treatment. However, no such article has been reported so far, but this possibility exists theoretically.

Do all patients have pathological changes of bone marrow MSCs? Not all. It is estimated that the function of bone marrow MSCs in patients may not be damaged in the early stage of the disease.

To be continued in Part Two…