Common questions (click question to find out more):
What are Stem Cells?
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 embryonic and adult Stem Cells?
Embryonic stem cells
Embryonic stem cells are derived from the undifferentiated inner mass of an embryo. They are able to multiply and grow into a human being when in the womb.
The use of embryonic stem cells for medical treatment is currently against the legislation. They are under very strict conditions with scientists being able to study them but not use them in any treatments unless part of a research study.
Pain in other parts of the body, particularly the lower back, can also cause pain to appear in your hip – this is known as referred pain.
Adult stem cells are found in the fully-grown human and have potential to differentiate into various tissues such as nerves, muscles, bone and cartilage.
These cells are less versatile than embryonic stem cells but can divide to replenish dying cells and regenerate damaged tissues.
What are minimally-manipulated and manipulated Stem Cells?
Adult stem cells can either be minimally-manipulated or manipulated.
Minimally-manipulated stem cells
Adult stem cells can be harvested from parts of the body which can be rich in these cells. These tissues include 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 but are not subject to the same rules.
Manipulated stem cells
These cells are harvested in the same way however following removal from the body the stem cells are separated in a laboratory. These cells are then grown 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 being used 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.
Prof Dr Philip Schoettle talks to the Regenerative Clinic about his uses of manipulated stem cells
Prof Dr Philip Schoettle, MD, currently treats patients at his private institute for orthopedics, sports injuries, and cell therapy in Munich, Germany; he also sees our patients on a scheduled basis in London at the Harley Street Specialists Hospital in Marylebone. He is a cell therapy surgeon and orthopedic specialist at Okyanos Center for Regenerative Medicine. Prof. Schoettle is a strong proponent of regenerative medicine and adjunctive approaches to surgical treatment of the knees, shoulders and other joints. An expert in reconstructive knee surgery, Prof. Schoettle’s depth of knowledge extends to general orthopedic treatments combined with state-of-the-art medical technologies and novel therapeutics.
Where are adult Stem Cells found?
There are two main types of stem cells in the adult. One is in the bone marrow and the other is found in fat (adipose) tissue.
Fat Derived stem cells
Bone Marrow Derived stem cells
Bone marrow stem cells are harvested with a technique called ‘bone marrow aspiration’ which involves drilling into the bone of the pelvis and sucking out some of the soft tissue from inside. This bone marrow is then usually centrifuged to concentrate the stem cells. It has been shown that the quality and the concentration of bone marrow stem cells deteriorates as we age. Younger individuals will have better functioning and greater numbers of stem cells in their bone marrow compared to an older individual.
How do Stem Cells work?
There are a number of ways that stem cells can work. In the laboratory, using very complex techniques, stem cells can become different kinds of tissue cells such as bone or cartilage. They are placed on scaffolds and then placed inside the diseased parts of the body to try regenerate these areas. This technique has been performed for the past twenty years and scientists have found varying degrees of success when trying to treat numerous diseases including arthritis.
More recently, scientists have realised that stem cells do not necessarily turn into a variety of different cells types within the body but it maybe that they act as marshals in guiding the regenerative process within the tissues that are injured. The stem cells work by secreting a variety of chemicals that act in the injured tissues. These chemicals help in the clean up of the damaged tissues and then work to recruit the undamaged parts of the same tissue to start regenerating and replacing what has been lost.
What are Mesenchymal Stem Cells (MSCs)?
“MSCs are one of the body’s greatest natural healing forces. Over the coming years there is no doubt that they will be utilized more frequently as the driving force behind new treatments that will improve healing and regeneration of tissues throughout the body”.
Mesenchymal cells are a subgroup of stem cells. They are only capable of making a certain type of tissues such as bone, cartilage, muscle and fat.
They 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 damage and 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 (known as tri-lineage differentiation). Originally identified within the bone marrow, these adult multipotent cells are present in even higher concentrations within fat tissue living on the surface of blood vessels, and in other organs and tissues at lower concentrations (placenta, cord blood, dental pulp et al).
They were originally described as MSCs by Arnold Caplan in 1991 referring to them as ‘medicinal signalling cells’ that can be identified by their expression of markers on the cell surface which include OCT4, Nanog and Sox2, CD73, CD90 and CD105 and a lack of blood cell markers such as CD34 and CD45. They also form colonies known as colony forming units [CFUs].
Fat or adipose-derived MSCs are of particular interest since here 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. There is therefore a great potential to utilize these cells in the treatment of injury and disease.
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.
How do MSCs work and what do they do?
MSCs 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 microRNAs, 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 such as TSG-6 and IL-1R-alpha antagonist that can clean, clear and completely attenuate the pathological ongoing inflammatory condition thereby enabling and promoting the healing process and at the same time providing long-term pain relief.
- Scar-less tissue healing and regeneration; MSCs produce vast quantities of molecules that support tissue regeneration including SDF-1, HGF, TGF-beta and VEGF that cause the host tissue to react producing more of its own healing substances creating the perfect environment for repair. When these cells have been injected or implanted into damaged joints, the natural healing processes of the body are vitalized and maximized.
- Innate immunity; MSCs can modify the body’s own immune responses. They secrete substances including IL-6, IL-10 and PGE2 that interact with the body’s white blood cells e.g. T-lymphocytes, instructing them to block inflammatory pathways, create the M2 type of anti-inflammatory macrophages, and significantly increase anti-bacterial activity protecting the injury site from infection.
Long-term delivery of this ‘medication’ is provided due to the extraordinary capability of the MSCs to release these substances enclosed in tiny parcels known as exosomes, and this provides a long-term capacity of delivery to be maintained, as long as the viability (capability to remain alive) of cells or tissue is maintained inside the body. Meaning that the beneficial effects could continue for months or years as long as the MSCs remain resident at the site of the injury. This has been shown to be the case particularly when they are used in conjunction with a carrier such as the original fat of origin which makes them ‘sticky’ and in effect constitutes a type of tissue graft rather than a simple injection of cells. The MSCs 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, ultimately, 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 MSCs to develop what is known as a Th1-phenotype- concomitantly releasing more anti-inflammatory molecules and providing enhancement of osteogenic and angiogenic (production of new blood vessels to aid healing) potential. There is an enormous potential to more highly ‘tune’ (optimize) the MSCs making them even more fit for purpose depending on the place within the body and the type of treatment required and this demonstrates a great future capability and capacity as a key therapeutic for healing.
The use of MSCs in clinical trials
There are currently over 1000 FDA-registered clinical trials, utilizing MSCs, ongoing with >20 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 MSCs. This could help in 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 concerted and 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 MSCs can strongly assist and support the natural healing processes.
What are the misconceptions with using Stem Cells?
There are many misconceptions around the use of stem cells. Below are two main examples.
1. That embryos and foetuses are destroyed in order to provide stem cell treatments
This is clearly not the case as the use of embryonic stem cells is illegal in both the United Kingdom and in Europe. The stem cells that are used for treatments are from an adult which are harvested from the same individual that is being treated.
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.
What is Platelet Rich Plasma Therapy and how does it differ to Stem Cell therapy?
What is Platelet Rich Plasma therapy? Platelet Rich Plasma (PRP) is derived from the blood. Blood has two main components, the fluid (the plasma) and the cells. The Red Blood Cells transport oxygen and the white blood cells are part of the immune system. The blood is taken from a vein in the arm and placed inside a centrifuge to spin the blood. Spinning separates the red and the white blood cells from the plasma which is in the fluid portion of the blood. Within the plasma there are tiny fragments called platelets, which along with the plasma, form clots. The clots are usually formed where the body is injured and within these clots are various chemicals and compounds that are integral to the healing process. PRP has been used for over 20 years to treat a variety of conditions including inflammation around tendons as well as arthritis in joints.
How does it differ to Stem Cells therapy?
PRP includes a number of compounds that the body uses for the healing process. It is thought that MSCs are the factories that produce these compounds. The difference is between the battery and the generator. The PRP is much like a battery which is pre-loaded with a certain amount of electricity, whereas, a generator (stem cell) can go on to generate as much electricity as is required. The cells are the factories which produce the compounds used for the healing process in great variety and amount.