A safer and more reliable source of MSCs

Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for clinical use due to their capacity for self-renewal, immunomodulatory properties, and tissue regenerative potential. For decades, MSCs have been studied in a great number of clinical trials for generally untreatable diseases, such as musculoskeletal disorders, myocardial infarction, stroke, graft-versus-host disease (GvHD), and autoimmune diseases. MSCs were originally isolated from bone marrow; however, similar cells have been found in other tissues, including adipose tissue, umbilical cord blood, amniotic fluid, the placenta, peripheral blood, dental tissue, skeletal muscle, and connective tissues of the dermis, skin, hair follicles and tonsils. Given that MSCs could exhibit different potentials for clinical applications depending on their origin, comparative studies on MSCs derived from different tissues have become essential. Several studies indicate that bone marrow-derived mesenchymal stem cells (BM-MSCs) appear to be much safer, more universal, and better to use to treat several chronic illnesses than other sources of MSCs.

It was recently shown that the regenerative therapeutic potential of MSCs mostly depends on its secreted soluble factors and regulations of cell-to-cell contacts rather than MSCs differentiation and engraftment in the patients’ body for rebuilding damaged tissues. On that account, it makes sense to further investigate MSCs secretomes to compare their potential clinical usefulness for the treatment of different disorders. Having said that, the results of these clinical trials were quite varying, including the results for the same type of disease. One explanation could be due to differences in culture conditions, different dosages of cells injected into the patient, cell delivery route, allogenic or autologous stem cell source, or conditions of immune systems of patients. In consequence, the development of suitable MSC culture protocols and dosages for the most effective treatment of various diseases have become of paramount importance.

Mesenchymal stem cells can be derived from different sources. The first is bone marrow-derived mesenchymal stem cells (BM-MSC), which are obtained from invasive bone marrow puncture and susceptible to aging factors, the accumulation of cellular damage, and senescence. Bone marrow was the first source reported to contain MSCs. On the other hand, umbilical cord blood was introduced recently as an alternative source that is attainable by a less invasive method. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) can be obtained from healthy tissue with noninvasive minimal ethical concerns, which explains its growing popularity in therapy. Another is adipose tissue, which comes across as another promising source MSCs.

The Mass Spectrometry proteomic analysis of the secretomes of MSCs derived from the bone marrow, umbilical cord, and adipose tissue revealed different profiles. Using Venn diagrams, a total of 451 proteins were identified, in which 134 proteins were common to the three MSCs populations. Interestingly, despite the different protein profiles of MSCs derived from different tissues, the functional analyses of source-specific secretomes revealed proteins that could promote cellular development, cell proliferation, and anti-apoptosis. Likewise, the biological pathways predicted are associated with cell proliferation and cell migration.

MSCs are known to recruit endogenous cells to repair lesions and regulate immune responses after infusion in patients' bodies. Thus, the difference between protein profiles of various MSCs populations could be valuable for clinical use. It was shown that the secretome of BM-MSCs might be optimal for reducing oxidative stress, while the UC-MSCs and AD-MSCs are more beneficial for reducing excitotoxicity. BM-MSCs secretome could have the prominent anti-oxidative properties when compared to UC-MSCs and AD-MSCs. Among the different sources of MSCs, gelsolin which is known as a stronger anti-oxidative molecule in neurodegenerative disorders such as Alzheimer’s disease, was only revealed in the BMSCs secretome.

Both BMSCs and UC-MSCs secretomes exhibit a similar anti-apoptotic profile, but with differences in the sole expression of SDF- 1α and Gelsolin by BM-MSCs, and CSF-1 by UC-MSCs (known as neuroprotective and anti- apoptotic agents). It was revealed that the set of genes related to antimicrobial activity and to osteogenesis was more expressed in BM‐MSCs, whereas a higher expression in UC‐MSCs was observed for genes that participate in pathways related to matrix remodeling via metalloproteinases and angiogenesis. In other words, BM‐MSCs would be more committed to osteogenesis, whereas UC‐MSCs would be more committed to angiogenesis.

It is well known that MSCs possess immunomodulating properties and can inhibit the proliferation and function of major immune cell populations such as T cells. It was demonstrated that in co-cultures of activated T cells with MSCs in vitro, only the BM- and AD-MSCs significantly inhibited T cell proliferation induced by PHA. Factors IL10, TGFB1, HGF, IL6, TNFAIP6, TSG-6 associated with the immunomodulatory effects of MSCs are differently expressed by its various types. In one investigation, it was demonstrated that BM-MSCs have elevated levels of IL10 and TGFB1 compared to the other MSCs. In another study, HGF was detected only in BM-MSCs, while TSG-6 and ITGB1 were expressed in UC-MSCs exclusively.

Moreover, some studies have shown that UC-MSCs are more functionally active cells, but the activity of some groups of genes is not beneficial relative to the therapeutic significance of these cells. For instance, it was shown that the expression level of a proto-oncogene JUN is significantly higher in UC-MSCs. However, the upregulation of such genes may lead to some unpredicted complications in the patient’s body after infusion and the possibility of turning UC-MSCs into cancer cells. That said, it is important to note that this does not prove that these types contribute to the appearance of cancer, although it can facilitate its development. On that account, BM-MSCs could be safer and more reliable compared to UC-MSCs due to their secretome showing few proteins that could create complications in the patient’s body. Needless to say, these findings need to be proven with more experimental methods and scientific approaches.

BM-MSCs also appear to be more universal, beneficial, and have more clinical approved studies done than other sources. MSCs derived from bone marrow can be safely implemented in several areas, including clinical, anti-inflammatory, anti-aging, and cosmetics. It was reported that 59% of the approved clinical trials done used BM-MSCs, while 17% used UC-MSCs,16% used adipose tissue, and 8% used other sources of MSCs. In addition, the proliferative and differentiation potential of BM-MSCs, as well as their cell quantity upon collection and cell quantity yield within four passages culture were found to be much higher than UC-MSCs and other sources.

Kintaro Cells Power offers BM-MSCs obtained from the bone marrow of young healthy donors who passed the strict screening tests. This allows us to guarantee the greatest effectiveness of therapy with Kintaro Cells. Of course, a sufficient number of injected cells is very important for the therapy to have a noticeable effect. Thus, we recommend injecting from 50-200 million cells dose at a time, depending on the characteristics of each particular case. In addition, we recommend performing multiple cell doses administrations in the first six months as an intensive course of therapy, followed by a maintenance course in the form of one or two injections of cell doses per year. As the extraction and cultivation processes of the cells are conducted through a high grade quality control, we only introduce an exceptionally fresh cell product prepared specifically for each patient, excluding freezing cells before shipment. Consequently, the cells produced by our company are 100% alive and functionally active, allowing us to expect the greatest effects from Kintaro Cells therapy as possible.