Mesenchymal Stem Cells Explained

Our professors, consultants and doctors are experts in the use of stem cells in therapies and treatments. The following content has been created by them to give a broad overview about stem cells, their purpose and potential uses.
   

At The Regenerative Clinic we exclusively offer our patients Micro-Fragmented Adipose Tissue (MFAT) and Bone Marrow Aspirate Concentrate (BMAC) therapies. These pioneering new treatments use your body’s own mesenchymal stem cells to treat pain and inflammation. These minimally invasive procedures are a possible alternative to surgical treatments and can be used after surgery to help healing. They harness the natural ability of repair cells removed from your body fat or bone marrow to target problems affecting discs, joints, tendons, ligaments and muscles. 

    

What are Stem Cells?

Stem cells are the body’s raw materials. They are young and immature cells. Stem cells are unspecialised and have yet to take on individual characteristics and reach their mature specialised form. They are the origin of all specialised cells. Specialised cells are specifically designed to carry out a particular role in the body. For example, red blood cells contain haemoglobin which allows for the transportation of oxygen.

The human body is made of a variety of different types of cells that come together to perform various functions. In comparison, this is much like a city. In order for the city to function there are groups of people that perform different tasks. Policeman keep the peace, cleaners keep the streets clean, water work engineers make sure that households have water and healthcare professionals look after the sick. Different groups of cells in the body perform functions in much the same way. The kidneys filter and clean the blood, the muscles allow us to move our bodies and our skeleton has a support function which works in synergy with the muscles to allow us to move. 

Similar to how individuals can be trained into different professionals, stem cells are groups of cells that have the potential to become any of the specialist cells in the body such as muscle, skin, bone, cartilage and blood. 

What are Mesenchymal Stem Cells (MSC's)?

Mesenchymal stem cells are a subgroup of stem cells. Mesenchymal stem cells are multipotent, meaning that they can produce more than one type of specialised cell, but not all types of specialised cells. MSC’s develop into the musculoskeletal system’s connective tissues. They can differentiate into cartilage cells (chondrocytes), bone cells (osteoblasts), tendon cells (tenocytes) and ligament cells (fibroblasts). These specialised cells each have their own characteristic shapes, structures and functions.

Mesenchymal stem cells originate from the primordial ‘mesenchymal’ tissue during embryological development. They have the unique capacity to recognise their environment within the body and release signals and chemicals that protect against injury and enable healing and regeneration; in addition, they have the capability to multiply and to convert into skeletal tissues to help produce new cartilage, bone or fat. This is known as tri-lineage differentiation. Originally identified within the bone marrow, mesenchymal stem cells are present in even higher concentrations within adipose (fat) tissue living on the surface of blood vessels.

Mesenchymal stem cells can be identified by their expression of markers on the cell surface (including OCT4, Nanog and Sox2, CD73, CD90 and CD105) and a lack of blood cell markers (CD34 and CD45). 

Where do Mesenchymal Stem Cells come from?

Mesenchymal stem calls (MSC’s) can be found in bone marrow and adipose tissue.

Bone marrow is a soft, spongy tissue found in large bones. There are two types of bone marrow – red bone marrow and yellow bone marrow. Red bone marrow contains hematopoietic stem cells (HSC’s) which mature into red blood cells, white blood cells and platelets. Yellow bone marrow contains MSC’s which mature into connective tissues.

Adipose tissue is more commonly known fatty tissue. It can be found under the skin (subcutaneous) or packed around internal organs (visceral). Adipose-derived MSC’s are of particular interest as they are found in the highest natural concentration within the body, extraction from the fat is far easier than for bone-marrow, and there is no reduction in numbers or potency/capability as we age.

mesenchymal stem cells
Mesenchymal stem cell
stem cells
mesenchymal stem cells

How do Mesenchymal Stem Cells (MSC's) work?

MSC’s react to injury by lifting off the surface of the blood vessels and moving towards the area of damage where they begin to produce very high concentrations of tissue and cell specific targeting substances known as growth factors (cytokines and microRNA) that support, maximize and direct self-repair and regeneration. These secretions significantly support recovery by:

  • Blocking excessive inflammation: primarily through production and local secretion of molecules (TSG-6 and IL-1R-alpha antagonist) that can clean, clear and reduce inflammation. This enables and promotes the healing process and provides long-term pain relief.
  • Scar-less tissue healing and regeneration: MSC’s produce vast quantities of molecules that support tissue regeneration (SDF-1, HGF, TGF-beta and VEGF). These molecules cause tissue to produce more of its own healing substances, creating the perfect environment for repair. When MSC’s have been injected or implanted into damaged joints, the natural healing processes of the body are vitalized and maximized
  • Innate immunity: MSC’s can modify the body’s own immune responses. They secrete substances (IL-6, IL-10 and PGE2) that interact with the body’s white blood cells, instructing them to block inflammatory pathways, create (the M2 type) anti-inflammatory macrophages, and significantly increase anti-bacterial activity protecting the injury site from infection.

Long-term delivery of growth factors is provided due to the extraordinary capability of the MSC’s to release these substances enclosed in tiny parcels known as exosomes. Delivery is maintained as long as the viability (capability to remain alive) of cells or tissue is maintained. This means that the beneficial effects could continue for months or years, as long as the MSC’s remain resident at the site of the injury. This has been shown to be the case particularly when they are used in conjunction with the fat the MSC’s were extracted from, which makes them ‘sticky’ and in effect constitutes a type of tissue graft rather than a simple injection of cells. The MSC’s seem to have an ‘intelligent’ perception of where they are since the content of and release of the exosomes (and other secretions) as well as the fate of the MSCs is determined by the environment in which they reside.

For example, a highly inflammatory, hypoxic (low oxygen) environment, often seen within an osteoarthritic joint will induce the MSC’s to develop what is known as a Th1-phenotype while releasing more anti-inflammatory molecules and providing enhancement of osteogenic (production of new bone) and angiogenic (production of new blood vessels to aid healing) potential. 

How does your Mesenchymal Stem Cell count change with age?

It has been shown that the number of mesenchymal stem cells and the functionality of these cells found in bone marrow decreases with age. However, the functionality and volume of mesenchymal stem cells derived from adipose (fat) tissue is not affected by ageing.

What is the difference between Embryotic Stem Cells and Mesenchymal Stem Cells?

Mesenchymal stem cells are harvested from the bone marrow or adipose (fat) tissue from fully matured adults. They are only capable of differentiating into connective tissue cells.

Embryotic stem cells are derived from the undifferentiated inner mass of an embryo. Embryotic stem cells are pluripotent. This means that they are capable of differentiating into any type of cell. 

embryotic stem cell

What are Minimally-Manipulated Mesenchymal Stem Cells and Manipulated Mesenchymal Stem Cells?

Minimally-manipulated mesenchymal stem cells can be harvested from  bone marrow and fat. Once removed they are then processed in a very minimal way before being used for treatment. This tends to mean that the cells are not cultured or altered in a laboratory before being used for treatment.

Minimally-manipulated stem cells are termed as such because they maintain the normal architecture of the body tissue that they have been retrieved from.  

Manipulated mesenchymal stem cells are harvested in the same way however following removal from the body the stem cells are separated in a laboratory. The stem cells are then cultured and multiplied under strict laboratory conditions before being used in a separate procedure for treatment. This process of manipulating stem cells is not allowed by legislation both in the UK and the European Union if they are intended for treatment. These techniques are allowed by the government for scientists to study and are occasionally used under very strict regulations in research studies run by various Universities.

What are common misconceptions about Stem Cells?

There are many misconceptions around the use of mesenchymal stem cells. Below are two main examples.

1. That embryos and foetuses are destroyed in order to provide stem cell treatments 
No foetuses are destroyed in stem cell therapies. Stem cell therapies exclusively use mesenchymal stem cells which are obtained from adult adipose tissue and bone marrow. 

The extraction or manipulation for clinical use of embryotic stem cells is illegal within the United Kingdom and European Union.

2. That stem cells can cure absolutely everything
This is certainly not the case as with any treatment modality, there are failures. In most orthopaedic treatments anywhere between 5-30% of individuals having a surgical procedure end up not having the full benefits that the surgical procedure intends. It is the same with a variety of non-surgical treatments including physiotherapy, manual therapy, injections of various compounds including steroids and of course, stem cell treatments. 

stem cell

What are the uses of Mesenchymal Stem Cells (MSC's) in clinical trials?

There are currently over 1000 FDA-registered clinical trials, utilising MSC’s, ongoing with more than 20 trials at phase-3 (used in the treatment of patients) world-wide. An excellent safety profile has been observed over this period. A clinical indications prediction scale (CLIP) based on the capability of a particular donor sample to activate protein markers in vitro, can be used to define the activity of a population of MSC’s. This could help in the future to predict probable super responders as well as those that may require optimization or alternative strategies in order to benefit from the treatment.

Repair or regeneration of body tissues is an extremely complex process, and one requiring the coordinated interaction of many different cells and substances. For this reason it ultimately has to be a process organized from within the body. However, the evidence is clear that supplementing the tissue with MSC’s can strongly assist and support the natural healing processes.

knee cartilage

Mesenchymal Stem Cell Regenerative Treatment for Osteoarthritis

Osteoarthritis is a degenerative joint disease that represents a growing healthcare burden, particularly in ageing populations. Traditional medical therapies have failed to alter the progression of this debilitating condition. Osteoarthritis has been conceptualised in terms of progressive loss of articular cartilage. Articular cartilage is a smooth tissue that forms a protective barrier across the end of bones where they come together to form joints.

In osteoarthritic joints, there is a noticeable lack of cartilage accompanied by synovial inflammation, joint effusions (swelling) and bone bruising, all of which contributing to pain.

Mesenchymal stem cells can be injected into the joint affected by osteoarthritis to prevent the worsening of, and in some cases reverse, the degeneration of cartilage and reduce swelling.

knees

What Mesenchymal Stem Cell Therapies does The Regenerative Clinic Offer?

At The Regenerative Clinic, we offer Micro-Fragmented Adipose Tissue (MFAT) and Bone Marrow Aspirate Concentrate (BMAC) mesenchymal stem cell therapies.

Micro-Fragmented Adipose Tissue (MFAT)

Micro-Fragmented Adipose Tissue (MFAT) has been used in more than 35,000 patients worldwide. It is an innovative system designed to harvest, process, and implant adipose cells. At The Regenerative Clinic, our procedure allows the mesenchymal stem cells, harvested from adipose (fat) tissue, to be ready to use quickly, meaning that the whole procedure is completed within a short, day-case visit to one of our clinics.

The MFAT procedure uses cutting-edge technology that gently processes your body’s own fat tissue in order, amongst other things, to cushion and support areas of injury or damage as your body heals itself. MFAT is injected precisely into areas of the body in order to help establish an environment that helps tissue healing and repair. MFAT tends to stay in the area where it is injected instead of being reabsorbed, allowing your body to maximise the benefits of MFAT for an extended period of time. Read more here.

Bone Marrow Aspirate Concentrate (BMAC)

Bone Marrow Aspirate Concentrate (BMAC) is a non-surgical, minimally invasive, regenerative treatment that harnesses the natural ability to heal the body through the assistance of biological growth factors. BMAC utilises the regenerative mesenchymal stem cells collected from bone marrow to aid in the acceleration of healing moderate to severe osteoarthritis and tendon injuries. Performed in a day-case outpatient setting, this innovative treatment harvests and implant mesenchymal stem cells from bone marrow. Read more here.  

Here are some terms used in relation to stem cells and their meaning:

  • Self-renewal: a stem cells ability to divide and produce copies of itself for an indefinite period of time
  • Totipotent: a cell able to form an entire organism. When an egg is fertilised, it is called a zygote.
  • Pluripotent: a cell able to form every type of organ and tissue in the body. An example of this is embryonic stem cells.
  • Multipotent: a cell able to form some but not all of the organs in the body. For example, haematopoietic (blood) stem cells which are found in the bone marrow are only able to form the cells that make up our blood. MSCs can form all cells from the mesenchyme that include carilage, bone, muscle and fat.
  • Differentiation: the process by which stem cells become specialised into specific tissues to perform particular tasks. An example is when a MSC differentiates to cartilage cells which is essential for healthy joints.

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