1. WHAT IS REGENERATIVE MEDICINE
2.1 POST BURN SCARS
2.3 CHRONIC ULCERS REGENERATION
WHAT IS REGENERATIVE MEDICINE?
Regenerative Medicine encompasses many medical fields – Orthopedics and Spine Surgery, Sports Medicine, Gynecology, Urology, Oncology, Dermatology, Plastic surgery, Vascular Surgery, Cardiac surgery, etc.
Regenerative Medicine is the branch of medicine that develops methods to regrow, repair or replace damaged or diseased cells, organs or tissues. Regenerative medicine includes the generation and use of therapeutic stem cells, tissue engineering and the production of artificial organs. It uses autologous blood, bone marrow or adipose components to stimulate the body’s own repair processes. A common source for regenerative cells and growth factors are bone marrow aspirate concentrate (BMAC), platelet rich plasma (obtained from one’s own blood) and adipose derived stem cells.
POST BURN SCARS
Accidentally touching something hot, like grabbing a pan right out of the oven, or getting scalded with boiling water can burn your skin. Chemicals, the sun, radiation, and electricity can also cause skin burns.
Burns cause skin cells to die. Damaged skin produces a protein called collagen to repair itself. As the skin heals, thickened, discolored areas called scars form. Some scars are temporary and fade over time. Others are permanent.
Scars can be small or large. Burn scars that cover a wide surface of your face or body can affect your appearance.
The amount of heat and how long it stays in contact with your skin determine whether you get a scar and how big it is. Burns are classified by how much of your skin they affect:
|First-degree burn||Second-degree burn (partial-thickness)||Third-degree burn (full-thickness)|
|damages epidermis (outer layer of skin)||✓||✓||✓|
|damages dermis (layer underneath epidermis)||✓||✓|
|may damage bones and tendons||✓|
|turns skin white or black||✓|
|damages nerve endings||✓|
First-degree burns often heal on their own without scarring. Second- and third-degree burns usually leave behind scars.
Burns can cause one of these types of scars:
- Hypertrophic scars are red or purple, and raised. They may feel warm to the touch and itchy.
- Contracture scars tighten the skin, muscles, and tendons, and make it harder for you to move.
- Keloid scars form shiny, hairless bumps.
Types of skin ulcers
Usually there is an underlying problem which causes the skin to be slow to heal. Causes include:
Ulcers caused by problems with blood circulation
The blood supply coming to the skin is needed for the skin to heal after it has become broken or split for any reason. If there is a problem with circulation, the break in the skin does not heal, and may persist, leaving an ulcer. This may be a problem with the veins, the arteries, or the smaller blood vessels. The kinds of ulcers caused by circulation problems are:
- Venous ulcers. These ulcers and their treatment are described in the separate leaflet called Venous Leg Ulcers. They occur when the circulation in your legs is not working very well. Fluid tends to pool in the legs because the veins don’t work well enough to pump the blood efficiently back to the heart (venous insufficiency). This type of ulcer is more common in people with varicose veins that have lead to associated skin problems such as varicose eczema. They are also more common if you are overweight or obese, or not very mobile for any reason. They can also occur when the circulation is damaged by a deep vein thrombosis (DVT).
- Arterial ulcers. These are caused by conditions affecting arteries – see the separate leaflet called Peripheral Arterial disease.
- Vasculitic ulcers. These are caused by a number of conditions which cause blood vessels to become inflamed. This is called vasculitis.
Ulcers caused by injury or pressure
- Injury. Most ulcers start off with an injury to the skin. Some are trivial; a little scratch or bite for example, which doesn’t properly heal for some reason, such as a circulation problem as above. Others may be larger skin injuries, or injuries which extend more deeply to tissue under the skin.
- Neuropathic ulcers. Some injuries to the skin occur because there is a problem with the feeling (sensation) in the skin. If you can’t feel your feet, for example, you may not be able to tell that a shoe is too tight, or the bath is too hot. So you end up with a blister or a burn, which can go on to become a skin ulcer, particularly if your circulation is not very good. Ulcers caused in this way are called neuropathic ulcers. Diabetes is the common cause. See the separate leaflet called Diabetes, Foot Care and Foot Ulcers.
- Pressure sores (pressure ulcers) are a common type of skin ulcer. Areas of skin become damaged due to a continuous pressure on them, usually due to a person not being able to move well. See the separate leaflet called Pressure Sores.
Ulcers caused by cancer
These types of skin ulcers are called malignant skin ulcers. They may be caused by skin cancers, or by spread of cancer from elsewhere. Cancers which can spread to the skin include breast cancer, and cancers of the head and neck or genital areas.
CHRONIC ULCERS REGENERATION
Chronic leg ulcers (CLU) are a common and complicated disease to treat, and result in high morbidity and significantly reduced quality of life. Normal wound healing consists of four overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Most ulcers heal when the cause is eliminated and the ulcer is treated with standard wound care. Some ulcers, however, are for various reasons locked in the inflammatory stage and do not heal. Regarding CLUs, most of the ulcers are caused by venous insufficiency or arterial ischemia, often secondary to diabetes, but some CLUs do not have an apparent underlying condition.
CLUs are a challenge for the physician, a significant physical and psychological setback for the patient, and a heavy burden on the healthcare systems. Thus, an American study reported an average cost of treating chronic venous leg ulcers of $9685 per patient per year. This reflects that these patients are difficult to treat, as the available treatment options are limited, leaving patients with a chronic condition severely affecting their quality of life. CLUs result in substantial use of the resources of healthcare systems regarding materials, hospital appointments, reduced working capability for the patients, and impairment of the patient in general.
Treatment with stem cells might be a new treatment option for these patients. Stem cells have the potential to differentiate into numerous types of cells . Over the last decade, stem cell therapy has shown great potential in the treatment of a variety of different conditions, such as orthopedic disorders, inflammatory diseases, hepatic failure, and autoimmune disorders . At the time of writing, adverse events have not been reported; therefore, stem cell treatment is currently regarded as safe. A review including more than 1400 patients found a favorable safety profile of adipose-derived stem cells (ADSC), but also highlighted the poor quality of most studies in regard to registering adverse events.
Adipose tissue is an excellent source of autologous ADSC and can be harvested easily compared with bone marrow-derived stem cells (BMSC) . Adipose tissue has in recent years surpassed bone marrow as the preferred source of mesenchymal stem cells. Besides being abundant, far easier to harvest, and with a lower risk of complications for the patient, adipose tissue additionally contains about 40 times more stem cells than bone marrow . A simple liposuction of the abdomen or inner thigh performed under local or general anesthesia is sufficient to harvest the required number of ADSC without any significant risk of complications . ADSC can be either freshly isolated or cultured. The culturing takes several days or weeks, and cannot be performed as a same-day procedure.
Stem cells are a heterogeneous pool of cells with numerous capabilities . They possess anti-inflammatory and neoangiogenic effects, secrete numerous growth factors, and can differentiate into various cells types. Many of these are known to be involved in the complex healing of wounds, although the exact capabilities and mechanisms of action of stem cells in wound healing are not yet fully understood. Research suggests that stem cells work though two mechanisms of action: firstly they attenuate the general inflammatory response and, secondly, they transform into cells involved in wound healing such as fibroblasts, myofibroblasts, antigen presenting cells, endothelial progenitor cells, and so forth.
Freshly isolated ADSC are far more heterogeneous compared with the quite homogeneous cells harvested from cultured ADSC. The greater variety of cell types in the freshly isolated ADSC could have a significant advantage in wound healing, compared with the far more limited number of different cells in cultured ADSC. In ADSC, endothelial, hematopoietic, and pericytic lineages represent 10–20%, 25–45%, and 3–5%, respectively, of the total nucleated cells.
Several methods of isolating ADSC have been reported . The most common is enzymatic isolation. Some techniques use simple centrifugation and vibration to isolate a stem cell pellet. Others are more complex and involve, for example, enzymatic (collagenase) dissolving of the adipose tissue. Fully automatic systems also exist. The different methods have advantages and disadvantages regarding the time required for the procedure, the need for advanced equipment/specially trained personnel, and financial cost. Data describing the efficacy of various methods are not available; therefore, no standardized method exists. In addition, the optimal method of application of ADSC is still undecided.
Various animal studies have documented the positive effect of ADSC in accelerating healing of chronic ulcers. The clinical translation is ongoing, with several clinical studies already published. The aim of this review is to describe the available data on the treatment of CLU with autologous ADSC by identifying published human studies and ongoing/registered clinical trials on the matter.