Stem cells – Nanovectors - 3D Prostheses
Medicine has reached levels unimaginable until a few years ago. We are facing an important historical period in which the treatments are less and less invasive to offer the patient an acceptable and sustainable lifestyle.
Among the most important discoveries of these years we find stem cells, nanovectors and 3D prostheses. These are just some of the methods that derive from many years of experimentation, today they are reality and in a few years they will find an ever wider application.
Stem cells are primitive, non-specialized cells, endowed with the ability to transform into different other types of body cells through a process called cell differentiation.
Stem cells are being studied by many researchers who try to exploit their innate characteristic of turning into other cells. The goal is to cure different diseases.
Stem cells can be taken from different sources such as the umbilical cord, the amniotic sac, the blood, the bone marrow, the placenta, the adipose tissues, the dental pulp.
The first example of the use of stem cells took place in the 1980s. Some researchers thought that perhaps healthy skin cells, capable of continually regenerating themselves, could be used to treat particularly serious burns, which otherwise in many cases could prove fatal. The hypothesis turned out to be right. The epithelial lining cells, which cover the inside and outside of our body, constantly need to be exfoliated and regenerated, and they succeed thanks to stem cells. A sort of “reserve” of cells not yet differentiated that at the moment of need can turn into skin cells and guarantee a replacement for life.
Another therapeutic area where stem cells have recently provided encouraging results in clinical studies is stem cell gene therapy: instead of replacing a defective gene (introducing a gene can be dangerous because it can go into any cell) the gene is corrected in stem cells, which are then given to patients. In this way all the daughter cells will be genetically corrected.
For over thirty years hematopoietic stem cells extracted from the marrow of healthy donors have been used for the treatment of bone marrow transplantation with variable results depending on the pathology considered. For about ten years, on the other hand, gene therapy approaches based on the use of autologous haematopoietic stem cells (of the patient) and viral vectors capable of correcting the genetic defect underlying the disease have been developed.
Then there are the mesenchymal cells, stem cells that release factors capable of regulating actions and mechanisms within the body. In this case, stem cells have more a therapeutic effect than a substitute: they give a stimulus and then disappear, as if it were a drug therapy through cells. For some years these cells have also been used in clinical situations characterized by serious states of inflammation and autoimmunity in which traditional anti-inflammatory drugs (such as cortisone) have failed.
The cardiovascular field is a bit complex and today clinical studies give an indication to protect, rather than regenerate the heart with rather modest results than others. In this case, cells taken from the peripheral blood or from the marrow of the patients are used, which are purified in the patient after purification. The main applications are two: myocardial ischemia (heart) and peripheral (vessels). The first with several conventional treatments that in some cases, however, do not give the desired effect, the second with little possibility of treatment.
Then there are more frontier therapies that have not yet arrived in the clinic such as tissue engineering. Process that also involves many other disciplines such as bioengineering, science and physics of materials. The dream is to arrive at the “production” of a completely artificial vessel that can be used as a natural bypass, for an ischemic myocardium reperfusion operation, and that does not undergo restenosis.
Another goal is to instruct myocardial cells to regenerate the heart after a heart attack. Another area of basic research linked to the screening of biocompatible materials that could be used to combine different cells and generate a tissue that can integrate and replace the dead or damaged one.
Those involved in cardiovascular tissue engineering are trying to follow an approach similar to the one followed for the cornea, where, however, everything is easier because the cells are of a single type and the structure of the tissue is laminar, formed by a single layer. The heart is more complicated, there are different types of cells, it has a more complex architecture.
The final goal is to build a tissue that can replace the missing or damaged parts of an organism. Or use combinations of materials to instruct the damaged tissue to go towards regeneration, through an operation of awakening the stem cells. These will be the frontier researches that will see a preclinical experimentation not before 5 or 6 years.
The use of nanoparticles capable of transporting drugs in cancer cells has been experimented for some time, but without having found a fairly effective system without side effects.
A group of researchers from the University of California at San Diego, the Massachusetts Institute of Technology (MIT) and the Brigham and Women’s Hospital in Boston has now developed a type of silicon-based “shuttles” capable of lighting up with sufficient intensity to highlight even small tumors, and that do not release toxic substances to the body when they degrade.
The silicon particles are injected near the tumor and, once they reach the cancer cells, they bind to it. The experiments carried out on mice showed that the luminescence – of an intense red, induced with ultraviolet rays after injection – persists for a few hours before disappearing when the particles dissolve, releasing the drugs.
The chemotherapy drugs are transported thanks to porosity created with an ultrasound system in the tiny structures. These are the first nanoparticles designed to minimize the side effects of this type of approach, in fact other materials, such as carbon nanotubes and gold, are able to perform the same functions, but present problems of toxicity.
The advantages of using nanovectors are different: they affect tumors more effectively and selectively, and require lower drug doses than standard therapies. Other advantages are related to the relatively large size of the particles (about 100 nanometers): they can carry greater quantities of chemotherapy and be filtered and more easily expelled by the kidneys once they are degraded.
The first clinical application of nanotechnologies was, therefore, anti-tumor therapy. There are a dozen “nanopharmaceuticals” currently in vast clinical use, and almost all of them are used in oncology. The goal is to move from the laboratory to the patient’s bed as quickly as possible, while maintaining safety guarantees, in various primary sectors of contemporary medicine, such as cardiovascular and neurodegenerative.
The translation process from research to the clinic is often more difficult than scientific research itself. In the US, investment in nanopharmaceuticals is now almost equivalent to that in conventional or biotechnological drugs. What are the other possible applications? In addition to the targeted release of antitumor drugs, there are the implantable nanoglytes to release low concentrations of substances for a long time that exploit the principle of diffusion in the nanochannels, or the «nano fluidic». Then they can also be applied to regenerative medicine, prevention and diagnostic protocols.
The basic consideration is that the vital process in biology is given precisely by microscopic objects that coordinate the nano objects and we imitate this flow: we create microscopic objects and load them with nano units that act as vectors.
The greatest difficulties in this path are given by biological barriers. That is, it is necessary to arrive in the right place at the right time to kill the cancer cell in a given patient, unlike another. In summary, cancer is a pathology of biological barriers that alter molecular and cellular transport.
To overcome this problem, it is necessary to optimize the characteristics of the nanoparticle, which is increasingly precise and able to complete its task. For example, it is known that the spherical shape is the worst for the effectiveness of transport: better the “half coconut” shape. Also they choose materials that easily degrade in the body, such as porous silicon, and that do not release toxic substances.
Created to reproduce small things, toys or objects, 3D printing is increasingly proving to be an exceptional tool used in the various specialties of surgery and protesis. It sounds like science fiction and yet this new technology is able to reproduce, with the most diverse materials, bones, mandibles, parts of the skull, the auditory apparatus and much more.
Recently in the USA a cardiac surgeon has successfully used this method to reproduce, with particular tissues, some parts of a young man’s heart, saving him from certain death.
As well as people traumatized in various parts of the body, new bones of the motor apparatus, mandibles or some fractured parts of the skull have been installed, perfectly reproduced with these innovative instruments.
In Hungary, an exoskeleton, 3D printed, has been reproduced with this technique, which allows walking to a paraplegic. At Cornell University in the state of New York, a 3D printer was used to recreate a wounded patient’s earlobe.
The Wake Forest Institute in North Carolina was the first to transplant laboratory-produced blisters using this technique. 3D printing can produce a hip prosthesis perfectly equal to the diseased one, in a single solution, including the spherical part that fits into the joint cavity.
The flexibility of the materials that are used allows the realization of tissues similar and compatible to human ones, bone grafts of various types, in what is called regenerative medicine.
Researchers and scientists are studying the possibility of producing, in addition to tissues, also blood vessels, nerve pipelines through the development of molecular engineering, of cell biology using the sophisticated technique of bio-printers. A new frontier has opened up for the world of health care and reconstructive surgery whose boundaries and applications cannot be imagined.
One of the most frequent uses is the realization of artificial limbs: arms, hands and legs. Prostheses, usually very expensive, can now be made quickly and with high quality materials. Above all, you can make perfect prostheses thanks to the computer design and the connected 3D printer.
The low cost of the prosthesis, combined with a very high quality, is important in younger patients. In fact, during growth, it is necessary to provide for a new prosthesis adapted to the new dimensions, so the 3D printing comes to our aid by creating new prostheses at a minimal cost.
Furthermore, on a psychological level it is very important for the patient that the prostheses are similar to the real limbs. The dimensional accuracy, the complex geometries that can be achieved with 3D printing and above all the wide range of more or less flexible materials, make this technology ideal for the bioengineering sector.