What are stem cells?

Stem cells are defined as all cells that are capable of dividing in their unspecialized form (self-renewal) and of developing into specialized cell types. This latter process is called differentiation. Differentiation is the process of developing immature cells into highly specialized cells in the adult organism, each tailored to its specific function. A fully differentiated cell is the culmination of a series of differentiation steps. Differentiated cells differ significantly in their morphology and function from each other and from their parent cells.

In 2006, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy published the four minimum criteria that classify a cell as a mesenchymal stem cell:

First, MSCs adhere to plastic when maintained under standard culture conditions. Second, they must be multipotent stromal cells capable of differentiation into osteoblasts, chondrocytes, and adipocytes. Third, they express the biomarkers CD73, CD90, and CD105. Finally, they must not express the following biomarkers: CD14, CD11b, CD34, CD45, CD19, and CD79.

All organs and tissues of the body originate from stem cells. Stem cells also form a crucial basis for the regenerative capacity of numerous organs. Among the various stem cell types, adult (or tissue-specific) and embryonic stem cells have gained particular importance in recent years. These two stem cell types can be distinguished from one another with regard to both their origin and their developmental potential. With this in mind, it makes sense that stem cells are designated as such when they can self-proliferate and, more importantly, differentiate into other cell types. They can therefore mature into various cell types. Furthermore, they influence neighboring cell types by releasing signaling molecules.

Stem cells repair, regenerate, have strong anti-inflammatory properties, positively influence immune modulation, and produce no side effects because they are the body's own. Stem cells are the "maintenance team" in the human body. They are attracted to and activated by inflamed, weakened, or damaged tissue and then exert their regenerative effects on site. Until they are activated, however, they remain dormant and inactive. Once activated, they perform their functions, multiplying, dividing, and differentiating into the affected and damaged or diminished tissue. In the case of a skin injury, for example, the activated stem cells begin to strengthen partially damaged cells and replace completely damaged ones. Stem cells are therefore crucial for skin renewal.

Unfortunately, stem cells are not infinitely available in the various areas, so an aging process becomes visible when the local stem cells run out or have been excessively consumed by inflammation, disease, toxic damage or injury, and a cure/repair can no longer be achieved.

In addition to their capacity for multipotent differentiation, mesenchymal stem cells (MSCs) serve, for example, in the bone marrow to facilitate the survival and differentiation of hematopoietic stem cells. Recently, this characteristic has been more broadly recognized as the stimulatory or "tropical" influence of MSCs on other cells. Several studies have been conducted to determine the secretory molecules produced by MSCs and to identify measurable concentrations of TGFβ, stem cell factor (SCF), insulin-like growth factor (IGF), epidermal growth factor (EGF), as well as granulocyte and macrophage colonies and stimulatory factors (G/M-CSF). For instance, recent findings suggest that these paracrine effects are responsible for the observed repairs following MSC therapy in conditions such as stroke, osteogenesis imperfecta, and myocardial infarction.

Furthermore, mesenchymal stem cells (MSCs) appear to be immunoprivileged and immunosuppressive. MSCs secrete immunosuppressive and anti-inflammatory cytokines such as interleukin-10, nitric oxide, and prostaglandins, which can prevent host rejection of transplants by modulating T cells. The regulation of T cells by stem cells appears to be antigen-independent, suppressing both primary and secondary T-cell responses through inhibition of cell proliferation.

Following the initial discovery of MSCs in bone marrow, numerous other MSC sources were identified, including fetal tissue, umbilical cord, cord blood, and placenta, as well as various adult tissues (skin, gums, periosteum, blood vessels, synovial membrane, endometrium), and especially adipose tissue. In fact, stem cells have been identified in almost all tissue types and organs, leading to the hypothesis that blood vessels themselves represent the in situ origin of MSC precursor cells—the so-called pericytes. Although mesenchymal stem cells have been identified and isolated from various tissue sources according to the same criteria, differences exist in their therapeutic efficacy.

In the fields of orthopedics and musculoskeletal regeneration, the use of adipose tissue as a donor site for stem cells has clearly become established, as it is easier and less painful and risky to obtain than bone marrow. Furthermore, it has been repeatedly demonstrated that the concentration of mesenchymal stem cells in adipose tissue is nearly 100 times higher than in bone marrow.

The clinical use of autologous fat-derived stem cells (ASCs) is therefore increasing rapidly due to promising results under a wide range of conditions. While advances in the use of cultured, modified, and induced pluripotent stem cells have been measured primarily under laboratory conditions, the use of autologous fat-derived pluripotent cells is advancing at the clinical level. Clinical and preclinical studies show that autologous fat-derived stem cells have been shown to survive after transplantation, exhibit pluripotent differentiation, and are anti-apoptotic (i.e., they prevent cell death) and have anti-inflammatory and angiogenic (blood vessel-forming) effects.

In clinical practice, fat-derived stem cells are often administered not as a pure isolate, but as a component of the stromal vascular fraction (SVF), a heterogeneous mixture of cells resulting from the mechanical or enzymatic processing of aspirated adipose tissue. SVF contains a variety of cells, including macrophages, various blood cells, pericytes, fibroblasts, smooth muscle cells, vascular endothelial progenitor cells, and fat-derived stem cells. The stem cell content in SVF varies considerably depending on the adipose tissue processing method used, ranging from less than 1% of cells (mechanical) to more than 20% (enzymatic). SVF cells can and should be safely isolated, quantified, and characterized in the procedure room immediately after fat harvesting, within approximately 90 minutes.

Besides orthopedics, with therapeutic approaches for osteoarthritis and bone regeneration, the use of mesenchymal stem cells has been described in the treatment of heart attacks, cosmetic procedures, inflammatory bowel diseases, chronic wounds, erectile dysfunction, and a variety of other conditions. The number of stem cells present at different donor sites varies slightly depending on the donor's age. Generally, using the most efficient methods, approximately 500,000–1,000,000 cells per gram of lipoaspirate tissue can be isolated with a viability of over 80%. The number of viable cells required to treat a specific condition has not yet been definitively established, as the data is still insufficient to establish a reliable dose-response relationship. However, it is considered certain that the use of autologous stem cells from adipose tissue does not result in any additional adverse effects.

The idea behind stem cell therapy is to transfer the same type of mesenchymal stem cell from areas that are rarely or almost never used (in our case, from highly potent adipose tissue) to where they are needed due to aging or injury. There, they exert various mechanisms that are necessary for perfect healing and regeneration.