Stem Cells

Stem Cells – or SCs – are unspecialised cells that can divide to give origin, at the same time, either to other stem cells (equal to the mother cell), or to the precursors of a cell progeny that will eventually give rise to terminally differentiated cells (mature cells).

Stem cells that can differentiate into any type of embrional stem cell tissues are called totipotent, those that can differentiate into some types of cells or tissues (Adult Stem Cell) are called multipotent (or pluripotent), and those that can generate only one cell type are called unipotent. The identification of these cells is facilitated by the presence of specific markers on their surface (CD: Cluster of Differentation).

Stem cells are essentially classified into two categories: 

Embryonic Stem Cells (ES Cells) are present in the inner region of the embryo, before its “attachment” to the uterine wall. These are totipotent cells, with a significant proliferation potential, and because of this, are in high demand for basic research purposes. They can be isolated, extracted and grown in vitro, with the result that, starting from a few dozens cells, cell lines of hundreds of million of intact stem cells can be obtained. Today, the use of embryonic stem cells is still a hotly debated topic

Adult stem cells (AS Cells) act to maintain tissues and, if possible, repair them, but their potential is not endless: when they are depleted, tissues and/or organs inevitably begin to degenerate. These cells possess a particular plasticity that enables them to differentiate into different cell types. This clearly paves the way for interesting perspectives and very significant therapeutic hopes for regenerative medicine.

Among adult stem cells, those present in adipose tissue, classified as mesenchymal stem cells, attract particular interest among researchers, since they are  pluripotent cells – that is to say, cells that can differentiate into different types of cells and/or tissues. Moreover, precisely because they are adult stem cells that do not belong to the “embryonic cell” class, adipose tissue cells raise no problems of an ethical nature.

Mesenchymal Stem Cells

There has been much interest of late in the use of adipose tissue as an alternative source of mesenchymal stem cells (MSCs), in particular with respect to bone marrow. The mononuclear portion of adipose tissue, called the stromal vascular fraction (SVF), was originally described as a resource for adipocyte precursors (Hollenberg et al., 1968). These cells resemble fibroblasts from a morphological standpoint, and can differentiate into preadipocytes and generate adipose tissue in vitro (Gaben-Cogneville et al., 1983).

Lipoaspirate

OSTEOBLASTS

CHONDROCYTES

NO INDUCTION CELLS (NI)

ADIPOCYTES

The non-adipocyte differentiation of the stromal vascular fraction occurs under specific conditions, andthe concept of “adipose-derived stem cell” was mentioned for the first time in a 2001 Tissue Engineeringpublication in which a research team headed by Patricia Zuk demonstrated that the stromal vascular fraction contained large quantities of mesenchymal stem cells. To be employed for regenerative medicine purposes, these cells should ideally:

  1. be found in large quantities (in the order of million/billion cells)
  2. be isolated with simple, non-invasive procedures
  3. be able to differentiate into different cell lines in a controllable and reproducible way
  4. be easily transplanted
  5. be treated in compliance with current GMP (Good Manufacturing Practice) guidelines

The cell adipose tissue satisfy all of the above mentioned criteria. Moreover, we should consider that, since obesity has gained ground in modern society, subcutaneous adipose tissue has become easily available in abundant quantities. To obtain adipose tissue, liposuction is a less invasive technique than bone marrow aspiration. In general, it can be affirmed that this technique is less invasive for the patient and does not represent a pathological condition. Small quantities of adipose tissue (from 100 to 200 ml) can be easily obtained under simple local anaesthesia. Furthermore, just one gram of this tissue contains approximately 5,000 stem cells, called Adipose-derived Stem Cells (ASCs) – approximately 500 times more abundant than those obtainable from a comparable volume of bone marrow. For these reasons, adipose tissue can be regarded as a rich source of mesenchymal stem cells.

Therapeutic applications of mesenchymal stem cells

 

The speed at which research on stem cells is evolving makes it difficult to set a clear boundary between what is already reality and offers a concrete treatment opportunity and what will very likely become possible in the very near future.

Yet biomedical research is focusing on using stem cells as a tool for regenerating many tissues or organs. To date, many studies have reported promising results for the future application of stem cells in the treatment of many pathologies.

We should consider that 21 clinical studies on stem cells were completed in 2010, and another 20 in 2011. (Trends in Molecular Medicine Vol. 16 No 5).

The pathologies studied are as follows:

  • Cardiovascolar (Myocardial Infarction, ischemic pathology, etc.)
  • Gastrointestinal (Crohn’s disease).
  • Renal (acute renal failure, kidney transplants, etc.).
  • Hepatic (cirrhosis, familial hypercholesterolemia).
  • Pulmonary (COPD).
  • Nervous (Neuroblastoma MS, Parkinson ALS, Ictus etc.)
  • Pancreatic (diabetes type 1 and 2).
  • Cutaneous (diabetes sores, systemic sclerosis)
  • Systemic (Sjögren’s Syndrome, Lupus, GvHD)
  • Bone/cartilage (bone fractures, Osteogenesis Imperfecta, cartilage defects etc.)

In particular, it is worth underlining the success of a recently completed phase I study, in which mesenchymal stem cells were administered to patients suffering from acute myocardial infarction. These patients exhibited an improvement in cardiac function (EF), a reduction of arrhythmias and an overall improvement of the patient’s state of health, compared to a control group receiving placebo. This without observing any significant adverse effects (Swiss Med Wkly 2012;142:w13632). Further studies will of course be completed in the forthcoming months, providing more useful information about the use of mesenchymal stem cells for the treatment of other pathologies.

In conclusion, we can affirm that, in the upcoming years, it will be possible to achieve a better understanding of the biology of mesenchymal stem cells and their therapeutic action – and cell therapy will become a new clinical paradigm, providing an effective treatment for many pathologies that are considered incurable today.