Growth Factors to Stimulate Angiogenesis

Today´s technology allows the surgeon to improve angiogenesis, by applying GF such as Vascular Endothelial Growth Factor (VEGF) These GF are obtained by Genetic Engineering from ischemic tissues. VEGF is vital for the development of blood vessels, it is found active in growing, developing and cicatrisation processes as well as in many pathological processes.

VEGF gene has been identified in humans in the 6p2134 chromosome. Different isoforms have been identified, depending on their affinity to heparin. Some of VEGF´s functions are increasing endothelial cell´s permeability, growth and migration. If administrated as a topic, it causes endothelial fenestration to generate capillaries. This also cooperates to a global increase vascular permeability.

VEGF is also useful to improve angiogenesis by stimulating endothelial cells migration and influencing the expression of molecules on cell´s surface.

In plastic surgery, VEGF has been used experimentally in expanding tissue areas that have suffered ischemia.

Angiogenesis induction is achieved when applying genetic engineering: A poorly irrigated area is injected with a DNA plasmid that codifies VEGF.

Padubidri performed abdominal island shaped flaps on rats, to cover both sides of the abdominal wall, based in only one pedicle. They thought that the contra lateral side will suffer necrosis. After lifting the flap one group was irrigated with a solution containing 5 ug of recombinant human VEGF and the other one with physiological solution. There was a significant improvement in flap´s vitality when injected with the recombinant GF.

Reent investigations have proved that normal cells respond to ischemia VEGF from their own DNA. Angiogenesis could be improved by transferring ischemic cells with aditional genetic sequences. Genetically modified cells could respond to ischemia by producing a greater amount of VEGF.

On the other hand, stem cell´s capacity to turn into blood vessels that could repair harmed circulatory system has been studied. In 1997 Jeffrey M. Isner proved that bone marrow´s cells could become progenitor endothelial cells and, produce blood vessels in a process known as vasculogenesis. During this process, new vessels are created from hemangioblsats. Hemangioblsata are bone marrow´s cells that are marked by a CD34 antigen. The main objective of these cells is to irrigate again the body areas that my be at risk because of a lack of circulation .

Fig. 215-6. Silicone guide tube. Growth factors application for nervous regeneration.

Even though angiogenic therapy is very promising, it is not completely proven to work in humans and even if it did, the proper way to administrate it still remains unknown.

Growth Factors and Nervous Regeneration

Many publications have proven GF´s neutrophilic action in vivo as a treatment for neurodegenerative disorders, brain damages and peripheral nerve injuries. Nerve Growth Factor-NGF is a peptide whose structure has 3 subunits, alpha, beta and gamma. Beta is the subunit related to biological effects. The gene that encodes the information for NGF has been cloned. This way it is possible to obtain recombinant NGF.

Insulin like Growth Factor -IGF-I, IGF-II, has 70 amino acids in it´s structure. It expresses in several tissues and increases during regeneration and reparation processes. They are formed in the spinal ganglion and the motor neurons of the spinal cord and transported though the axoplasm to the peripheral nerves. They are abundant in the Schwann cells when a nerve has been harmed.

Fibroblast Growth Factor-FGF is mitogenic for many cells including fibroblasts, endothelial cells, astrocytes and Schwann cells therefore they have an important roll in nerve regeneration.

Platelet Derived Growth Factor-PDGF is located in most human tissues and with its receptors it actions directly on regeneration. It is also a coadjuvant for other GF´s stimulation.

A study done by Toriumi describes the physiopathology of the events that take place after neurological harm. It shows the use of a silicone guide tube between the two ends of the nerve. This provides a micro-environment for nerve regeneration using GF. This study was performed rat´s injured sciatic nerve. (Fig. 215-6).

On the other hand, paralysis caused by brain damage can be significantly reversed using small thoracic nerves grafts combined to GF. This was proved by Vernon Lin .

Growth Factors in Bone Regeneration

It is well known that several GF stimulate bone formation in vivo, Insulin like Growth Factor -IGF-I, Fibroblast Growth Factor-FGF, Platelet Derived Growth Factor-PDGF, Transforming Growth Factor Beta 44. Many studies have been focused on using morphogenetic bone proteins (BMP). These proteins have been isolated and produced in a recombinant way. This way they provide the possibility to avoid using conventional bone grafts in a near future.

Some of these proteins are able to induce heterotopic bone through endocondrial ossification. In vitro, bone morphogenetic proteins are able to induce osteoblast differentiation and mysenchemal cells; they can also stimulate or inhibit cell proliferation. In vivo, these proteins can transform primitive mysenchemal cells into osteoblasts, they also act stimulating monocyte´s migration. This way they initiate and promote the bone formation cascade. The best way to apply these proteins is about to be discovered. BMPs will have a very important role in bone defects reparation .

Growth Factors and Cartilage Formation

In reconstructive plastic surgery, autologous cartilage grafts are used to replace harmed or pathologic tissue, especially in nose and ears. Still, this procedure is hard to perform, mainly because of a lack of donor areas. Farming Cartilage studies have been done in which the chondrocytes are classified after been taken from nasal septum cartilage and treated with Transforming Growth Factor Beta and Insulin like Growth Factor type 1.

This is how; autologous cartilage can be obtained in important amounts in very short periods of time.

On the other hand, one of the most innovating fields of the latest investigations involves the possibility of using stem cells to create tissues that can be used in medical treatments and surgical interventions. A system that allows polymer materials to direct stem cell´s growth and development by acting as platforms has been developed. In order to do this, polymeric gels would be implanted in the joints of artistic patients. As we said, these gels act as structures for bone marrow stem cells to create new cartilage.

Stem cells would be obtained from the blood that gets to the joint area during the implantation. Once the new tissue is obtained, the polymer would biodegrade. The main objective of this scientific advance in arthritis treatment is to allow patients to regenerate their own cartilage and to avoid prosthesis implantation. Stem cells need surrounding substances to guide them (including Growth Factors). These substances are produced bay other cells. Stem cells also need mechanical attraction forces to be able to change into mature cells and therefore generate new tissues .

Figs. 215-7 and 215-8. GF rich Plasma in facial rejuvenation