Stem cells and mesenchymal stem cells


What are stem cells?

The term “stem cell” generally indicates a non-specialized cell, capable of differentiating itself by specializing in one of the many different cell types present in our body (i.e. a neuron, a white blood cell or a skin cell).

Stem cells are classified based on their ability to differentiate into cells that make up one or more body tissues.

Those capable of giving rise to any cell of the organism are called “totipotent”; only embryonic stem cells (that is, taken from embryos in the early stages of development) have this ability.

Cells capable of specializing in all cell types derived from one of the three germ layers that make up the embryo are “pluripotent”. These are the so-called three embryonic layers, from each of which only certain types of tissue originate: the endoderm (that is, the lining of the internal organs), the mesoderm (from which muscles, bones, blood and urogenital tract) and the ectoderm (which gives rise to the epidermis and nervous tissue).

Stem cells that give rise to only a limited number of cell types are defined as multipotent. This is the case with blood stem cells, which can make red blood cells (which carry oxygen) or white blood cells (which are part of the immune system), but not other types of cells.

The “oligopotent” stem cells can give rise to several types of cells belonging to the same organ: this is the case of the vascular stem cells which form the muscular wall of the blood vessels or the endothelium, ie the internal lining structure of the vessel.

Finally, “unipotent” stem cells are the least versatile: they recreate only one type of cell. The classic example is that of the hepatocytes, the liver cells, capable of reconstructing part of the organ if this is removed and nothing else.

If taken in the very early stages of development, embryonic stem cells are totipotent, otherwise they are pluripotent.

What processes characterize stem cells?

Through self-renewal, a cell is able, during replication, to give rise to a copy identical to itself. In fact, when a stem cell divides, at least one of the two daughter cells does not undergo any modification and remains, in all respects, the same as the mother cell. This allows the stem cell reserve of a tissue to remain quantitatively stable over time. As disease or aging progresses begins, this ability weakens.

With differentiation, however, a stem cell can specialize in the specific function of a tissue, such as: being a skin cell (keratinocyte), a muscle cell (myocyte), a cell of the nervous system (neuron). Differentiation is a progressive process that occurs through epigenetic modifications, i.e. modifications capable of silencing parts of the DNA that are not useful for that specific function. In this way, only the genes of the specialized cell remain active and what was once a stem cell can now replace the damaged cells and contribute to the functioning of a tissue.
Based on the state of potentiality, there are different types of stem cell: (a) unipotent, able to generate a cell of a single line commissioned and specialized in its functions; (b) multipotent, able to differentiate into certain cell types; (c) pluripotent, able to differentiate into all cells of an individual; (d) totipotent, capable of differentiating like pluripotent and also present in extra-embryonic tissues (ie not belonging to the fertilized cell). Different types of stem cells can also be recognized on the basis of their origin: (a) embryonic, totipotent cells present up to the 14th day of life, which are then transformed into multipotent stem cells; (b) fetal, multipotent cells that make up the fetus; (c) adult, multipotent, and pre-commissioned unipotent found in the tissues of an organism; (d) from umbilical cord blood, similar to adult multipotent blood, but present in abundance.

The next paragraphs will help us understand these differences with some examples.

What are mesenchymal stem cells?

Mesenchymal cells are adult stem cells which, as the prefix mes- suggests, can differentiate into all tissues of mesodermal origin (the mesoderm is an embryonic layer from which all the musculoskeletal system, blood cells and other organs originate). They were first identified in bone marrow in 1970, then in other tissues and, only in 2001, in fat. In regenerative medicine, they are highly appreciated for their simplicity of collection and use. Even if they cannot differentiate into all cell subtypes, they are able to perform excellently a capacity of stem cells that we have not mentioned so far: releasing, in response to the environment, molecules capable of promoting regeneration.

Mesenchymal stem cells (MSCs) are capable of producing different types of skeletal tissue cells, such as cartilage, bone and fat. Scientists are studying how MSCs can be used to treat diseases or lesions about bone, cartilage and even peripheral nerves . MSC research is also exploring therapies for other types of diseases, but the scientific basis for these applications is still being established and validated.

Some MSC-based treatments are being developed to help repair bone and cartilage, such as meniscus tears in the knee, or long-term accumulated damage leading to osteoarthritis.

Some studies are investigating preliminary results showing that MSCs help the formation of new blood vessels in damaged tissue. This could have significant implications for treating tissue damaged by heart attacks or disease.

Researchers are also examining the ability of MSCs to reduce inflammation, slow the progression of autoimmune diseases and prevent transplant rejection.

It is still not fully understood how MSCs can be successfully deposited in damaged body tissues.

What are haematopoietic stem cells?

The haematopoietic stem cell is a non-differentiated, pluripotent cell, progenitor of all the fundamental elements of blood: red blood cells, white blood cells and platelets.

HSCs are capable of proliferating while maintaining the potential to replicate itself. In other words, it is capable of reproducing itself and, at the same time, producing daughter cells which, through successive processes of differentiation and maturation, will give rise to the mature elements.

Precisely because of this characteristic, HSCs perform and maintain their function throughout life.

If we think that the daily requirement of “daughter cells” is 10¹¹-10¹² cells (100,000,000,000-1,000,000,000,000) it is easy to understand the proliferative potential of HSCs.

This type of cells has the ability to reconstruct the entire hematopoietic system of a person made aplastic in the long term. It therefore has both the ability to differentiate into the various hematopoietic lineages, and to self-replicate. Mature blood cells are in fact destined to live from a few hours to a few weeks before being destroyed. This continuous renewal is ensured by this small population of stem cells, which can be calculated at around 0.05 of the entire bone marrow population. The mechanisms that induce a stem cell to replicate and differentiate have not yet been clarified: hematopoiesis requires a series of highly complex processes which probably include the role of the microenvironment and the consequent production of cytokines. It is believed that the stem cell in resting conditions is blocked in the quiescent phase (G0 stage of the cell cycle), which would protect the cell from external insults. The intimate contact with the cells of the microenvironment (fibroblasts, macrophages and endothelial cells) partially regulates the processes of self-renewal, differentiation, proliferation and maturation.

Thanks to the possibility of an immunological characterization (positivity for the CD34 antigen), it is possible to collect stem cells using machines called cell separators. The transplantation of hematopoietic stem cells, obtained from peripheral blood or bone marrow, represents a consolidated therapeutic application for patients affected by solid tumours or blood diseases (leukaemia, lymphoma, myeloma). Other possible applications are the transplantation of cutaneous stem cells for extensive lesions or targeted cell therapies for some neurodegenerative diseases (Parkinson’s disease, amyotrophic lateral sclerosis) or musculoskeletal diseases (primary myopathies, osteogenesis imperfecta, etc.), for regeneration of cardiac tissue and blood vessels.

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