Adipose-Derived Stem Cell Therapy

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1 22 Adipose-Derived Stem Cell Therapy Damir Hudetz, MD, PhD, orthopaedic surgeon and Head of the Department of Orthopaedics at St. Catherine, Specialty Hospital in Zabok, Croatia, briefly described Stem Cell Therapy and the challenges in the field of orthopaedics in the future. Author: Katarina Bertoncelj Expert review: Damir Hudetz, MD, PhD, orthopaedic surgeon, St. Catherine IN NOVEMBER 2015, YOU PERFORMED THE FIRST AUTOLOGOUS ADIPOSE-DERIVED STEM CELL TRANSPLANTATION IN THIS PART OF EUROPE. WHAT ARE THE CHARACTERISTICS OF THIS METHOD? For more than a year, being the first in South-East Europe, we have been using autologous stem cells derived from the adipose tissue. The Lipogems technology, patented in 2010 and clinically available since 2013, represents a new and completely closed tool for harvesting, washing, processing, and reinjecting human lipoaspirates. It has to be emphasised that the procedure is not a classical cell expansion but exclusively the application of autologous cells, which include many mesenchymal stem cells, perycites etc. As the technique is highly sophisticated, the possibility of adipose-derived products contamination is significantly reduced. The procedure can be used on one or more joints. The treatment aimes at improving the function of the joint and reducing the pain.

2 23 WHAT IS ADIPOSE-DERIVED STEM CELL THERAPY? It is a treatment method which uses fat tissue as an optimal source of mesenchymal stem cells. A single gram of adipose tissue contains 500 times more pluripotent cells than 1 gram of bone marrow aspirate. Its potentials are support, cushioning, filling of soft tissue defects as well as healing and regenerative capabilities.

3 24 Damir Hudetz, MD, PhD, orthopaedic surgeon at St. Catherine WHAT KIND OF PATIENTS ARE SUITABLE FOR THIS PROCEDURE? The procedure is carried out in patients with different stages of articular cartilage injuries. It is known that after an injury, the articular cartilage can hardly or perhaps never regenerate, especially because there are no blood and lymph vessels nor nerves. Eventually, most cartilage injuries lead to swelling and pain in the joint, while arthritis occurs when articular cartilage is damaged or worn off. It is recommended that patients visit us in the early stages of degenerative cartilage changes, because the results of Lipogems technology are better. What are the results of the method? Lipogems has proved to be very effective mainly in clinical regenerative cases, although adequate scientific support from formal clinical trials is needed to confirm these promising results. Based on clinical results from more than 800 patients worldwide (obtained from many European and American colleagues), the intra-articular injection of Lipogems to treat knee, ankle, hip and shoulder osteoarthritis resulted in a surprising improvement in symptoms, with 100% safety of the procedure. Recently, Professor C. Zorzi and Dr. A Russo from the Sacro Cuore-Don Calabria Hospital, Verona, Italy, reported the results from 170 patients affected by knee chondropathy who had received a single intra-articular injection of Lipogems. They concluded that despite of the heterogeneity of the population, the trend shows significant improvement. Only two adverse events (abdominal haematomas) were reported in 170 patients. One gram of the adipose tissue has up to 500 times more pluripotent stem cells than the bone marrow. What is the potential of the adipose tissue in regenerative medicine? Indeed, 1 in every 100 adipose tissue cells is a mesenchymal stem cell (MSC), compared to 1 in every 100,000 bone marrow cells. Furthermore, it is widely recognised that the viability and the differentiation capacity of the bone marrow-derived mesenchymal stem cells (MSC) decrease with the increasing age of the donor. Fat tissue is available in large quantities in most patients and can be harvested easily, with a minimally invasive approach (under either local or general anaesthesia), offering highly viable mesenchymal stem cell (MSC) population with an optimal differentiation potential, independent of the donor s age. The regenerative potential of the adipose tissue-derived mesenchymal stem cells (MSC) is similar to that reported in other tissues. In your opinion, in which direction does the modern orthopaedics have to turn? A new wave of scientific and biotechnological revolution brought very fast development of the regenerative orthopaedics. It is a new interdisciplinary discipline which tries to stop or delay aging, and accelerates the process of locomotor system healing. With the state-of-the-art discoveries in the field

4 25 Katarzyna of molecular and cell biology, clinical medicine and engineering, the final goal of the regenerative orthopaedics became tissue regeneration or complete regeneration of the injured tissue in the locomotor system. The principal concept of the regenerative medicine lies in the understanding and the exact coordination of the relation between three basic parts of the regenerative triangle: the cell, its surroundings (biological signal) and the carrier (scaffold). Autologous chondrocyte implantation, platelet-rich plasma and cell therapy with mesenchymal cells are the perfect examples of the personalised medicine put in practice. Jadranka Primorac, board member of the Hospital for finance and strategic issues provided us with a short description of the clinic and the stories which have been written so far. How do you see the future of the regenerative medicine? What can we expect from personalised medicine? Just recently, it seemed distant, but now the role of personalised medicine in everyday clinical practice has been growing. Medical staff have to adapt and get additional training in genomics, proteomics and their clinical use. It is undisputable that doctors will not treat their patients with regular treatment algorithms, but will have to introduce the findings based on the latest achievements in the field of molecular and cell biology, clinical medicine and tissue engineering, in order to achieve the correct diagnosis, preventive measures and therapy optimisation. Implementation of personalised medicine in everyday clinical practice will include interpretation of genetic data. This has important long- and shortterm benefits, particularly in chronic and complex diseases. Nowadays, pharmacogenomics as an integral part of personalised medicine cannot be avoided, and in the near future, pharmacogenetic analysis will be introduced to St. Catherine s routine practice. The goal of pharmacogenetics is to understand how the genome of an individual affects the therapeutic efficacy of medicines and the occurrence of undesirable side effects. What does personalised medicine mean to you? Individual approach to diagnostics and treatment can strongly improve the activity of healthcare and reduce unnecessary expenses of the State budget. Genos, one of the leading genetic laboratories, and our hospital are developing one of the first integrative concepts of the optimised treatment in Europe, using the methods of personalised medicine also involving molecular diagnostics, including coagulation factors and DNA tests, with the aim of prescribing optimised therapy

5 26 in conformity with pharmacogenetical findings. The above mentioned approach is extremely important for patients waiting for surgical procedures. You treat foreign patients who come from Europe, North Africa, the northern part of Iraq and Saudi Arabia. Could you share some experience from treating foreign patients? It is true, patients were diagnosed or treated in our clinic come from almost every continent. Since the hospital is also the centre of excellence for sports medicine, many top athletes were treated here, from Garry Kasparov, Marin Čilić, Luka Modrić, Ivan Rakitić and other football players to fourtime Olympic medal winners Ivica and Janica Kostelić and others. Could you share a story associated with the successful treatment of a foreign patient? There are many stories like this, but I would like to single out the case of a Russian girl from Moscow who suffers from the most difficult form of brittle bone disease, type III osteogenesis imperfecta. During her childhood, she suffered ten bone fractures. After her bones healed up, they were crooked, and until now she could not find proper orthopaedic treatment. After her last fracture in March, her doctor from Moscow contacted us and the demanding preparation for her arrival started. In the 7-hour-long surgical procedure that followed, the 11-year-old girl had telescopic screws put in her femurs. She had deformations from 30 to 50 degrees on both femurs, which we had to correct in a way to straighten the bone in profile and en face projections. Fourteen members of the hospital staff participated in the preparation for the surgery, diagnostic examinations and the surgery itself. dpm75@123rf.com Ivica Kostelić, Croatian ski racer, who won four Olympic silver medals and a set of medals (gold, silver and bronze) in the World Championships and who has 26 victories in World Cups, the big Crystal Globe from the 2010/2011 season and two small Crystal Globes, from the 2001/02 season in slalom and the 2010/11 season in the combined. sportgraphic@123rf.com Currently, the young girl undergoes physical therapy in Russia and will soon return to St. Catherine for her second surgery of the bones below the knee, which will enable her to move autonomously. Even the Russian doctors give us credit for an incredible success. Luka Modrić, Luka Modrić, Croatian football player, who currently plays for Spanish Club Real Madrid, where he moved in August 2012 after leaving Tottenham.