St. Catherine Hospital is “The Center of Excellence” for cartilage defect treatment with mesenchymal stem cellsThis procedure was launched in St. Catherine Hospital in November 2015.

Working hours:Zagreb: Monday - Friday 8 am - 8 pm

Zabok: Monday - Friday 8 am - 8 pm

LIPOGEMS®

Application of Mesenchymal stem cells therapy

St. Catherine Specialty Hospital

Bračak 8 / 49210 Zabok / Croatiaphone +385 49 296 600 / Fax +385 49 296 699 / info@svkatarina.hr

Polyclinic St. Catherine

Trpinjska 9 / 10000 Zagrebphone +385 1 286 74 00 / Fax +385 1 286 74 99 / info@svkatarina.hr

www.svkatarina.hr

days of excellence

Lipogems® Clinical ApplicationLipogems® 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. The very low infection risk is a result of the produc-tion of the antimicrobial molecule LL-37 (1). Based on clinical results from more than 800 patients worldwide (obtained from many European and American col-leagues), the intra-articular injection of Lipogems® to treat knee, ankle, hip, and shoulder osteoarthritis re-sulted in a surprising improvement in symptoms, with 100 % safety of the procedure. In addition, single-case reports have demonstrated that intra-articular injec-tion of Lipogems® in patients with osteoarthritis and nonresponsive knee pain in association with meniscal damage seems to improve joint functionality (5) and recently it was published that intra-articular injection of Lipogems® improved knee function in a patient with a posttraumatic lesion of the cartilage (5). The im-provement in measured outcomes for pain, quality of life, KOOS (Knee Injury and Osteoarthritis Outcome Score), and MRI imaging showing sustained gains up to 6 months (6).Professor C. Zorzi and dr. A Russo from Sacro Cuo-re-Don Calabria Hospital, Verona, Italy recently re-ported results on 170 patients affected by knee chon-dropathy to whom a single intra-articular injection of Lipogems® was applied. They concluded that despite of the heterogenity of the population, the trend is of sig-nificant improvement. Out of 170 patients they report-ed only two adverse events (abdominal hematoma).Professor Joseph Purita, Director of the Institute of Re-generative and Molecular Orthopaedics in Boca Raton,

Florida who is among pioneers in the use of stem cells and platelet rich plasma PRP), highlighted that the Li-pogems® technique so far has been utilized in over 5,000 patients. In our recent study, 16 patients (30 knees) were examined at baseline and at 3, 6 and 12 months after Ad-MSC ap-plication. Our data suggesting that the use of adipose de-rived mesenchymal stromal/stem cells (Ad-MSC) ther-apy in patients with osteoarthritis result (measured by dGEMRIC MRI) increased glycosaminoglycans (GAGs) content deposition in hyaline cartilage. Those results are in line with secondary outcome measurements including quantitative MRI analysis, KOOS and VAS.However, now, several clinical trials are under way to support the initial encouraging outcomes. Lipogems® is a minimal risk procedure: in fact, it would be considered the safest technique of this kind.Literat ure:1. Tremolada, C., Colombo, V. & Ventura, C. Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development. Curr Stem Cell Rep. 2016;2:304-312. doi:10.1007/s40778-016-0053-5.2. Tremolada C, Beltrami G, Magri A, Bianchi F, Ventura C, Di Vito C, Campanella R, Navone SE, Marfia G, Caplan IA. Adipose Mesenchymal Stem Cells and “Regenerative Adipose Tissue Graft” (Lipogems) For Musculoskeletal Regeneration. European Journal of Musculoskeletal Diseases. 2014;3(2): 57-67.3. Ceserani V, Ferri A, Berenzi A, Benetti A, Ciusani E, Pascucci L, Bazzucchi C, Cocce V, Bonomi A, Pessina A, Ghezzi E, Zeira O, Ceccarelli P, Versari S, Tremolada C, Alessandri G. Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells. Vascular Cell. 2016;8:3. doi: 10.1186/s13221-016-0037-3.4.Bosetti M, Borrone A, Follenzi A, Messaggio F, Tremolada C, Cannas M. Human Lipoaspirate as Autologous Injectable Active Scaffold for One-Step Repair of Cartilage Defects. Cell Transplantation. 2016; 25:1043–1056.5.Striano R, Chen H, Bilbool N, Azatullah K, Hilado J, Horan K. Non-responsive knee pain with osteoarthritis and concurrent meniscal disease treated with autologous micro-fragmented adipose tissue under continuous ultrasound guidance. CellR4. 2015; 3 (5): e1690.6. Franceschini M, Castellaneta C, Mineo G. Injection of autologous micro-fragmented adipose tissue for the treatment of post traumatic degenerative lesion of knee cartilage: a case report. CellR4. 2016; 4 (1): e1765. 7. Hudetz D, Borić I, Rod E, Jeleč Ž, Radić A, Vrdoljak T, Skelin A, Lauc G, Trbojević Akmačić I Plećko M, Polašek O, Primorac D. A year follow-up study of Ad MSC therapy in patients with knee osteoarthritis. Book of Abstracts. The Tenth ISABS Conference on Forensic and Anthropologic Genetics and Mayo Clinic Lectures in Individualized Medicine. Dubrovnik, June 19-24, 2017.

Meet Our Physician Team

Dr. Damir Hudetz, M.D., Ph.D., orthopedic surgeon

Dr. Eduard Rod, M.D., orthopedic surgeon

Dr. Andrej Radic, M.D., orthopedic surgeon

Dr. Željko Jelec, M.D., Ph.D., orthopedic surgeon

Dr. Trpimir Vrdoljak, M.D., orthopedic surgeon

Dr. Alan Ivkovic, M.D., Ph.D., orthopedic surgeon

Application of Mesenchymal stem cells therapy

The use of adipose tissue has taken on increasing importance in the field of regenerative stem cell therapy. This therapy can be divided into two major pathways. One pathway involves plastic and reconstruction surgery. The other major pathway involves orthopedics and its related fields. New therapeu-tic approaches, such as the use of mesenchymal stem cells (MSC), seem to show promising preliminary results when ap-plied in the context of joint degeneration and osteoarthritis. MSCs were first reported by A. Caplan in 1991. MSCs have ex-tensive proliferative ability in culture in an uncommitted state, while retaining their multilineage differentiation potential, which makes them attractive candidates for biological cell-based tissue repair approaches. The controversial and often poorly understood roles of MSCs are slowly being elucidated and the regenerative capabilities of fat (adipose derived stem cells, ADSCs), with mesenchymal properties, are being widely explored. Through trophic, mitogenic, anti-scarring, anti-apoptotic, immunomodulatory, and anti-microbial actions, produced by a plethora of bioactive elements, growth fac-tors and cytokines, these cells “sense” and “signal” changes in the microenvironment where they reside. More recently, perivascular cells (pericytes) have been reported as the origi-nators of MSCs. Adipose tissue is rich in vascular niches, that provide a readily available source of native cushioning, and could serve as a source of potential healing and regenerative tissue containing ADSCs.

Fat Tissue PotentialThe idea that fat tissue is an optimal source of mesenchy-mal stem cells (MSC), is supported by the abundance of these cells in this tissue compared with other tissues, such as the widely-used bone marrow, and by their easy access. Indeed, 1 in 100 adipose tissue cells is a mesenchymal stem cells (MSC), compared with 1 in 100,000 bone marrow cells. Moreover, bone marrow harvesting is an invasive and traumatic procedure compared with lipoaspiration and is performed under general anesthesia with a higher risk of viral infection. Finally, it is widely recognized that the vi-ability and differentiation capacity of bone marrow-derived mesenchymal stem cells (MSC) decreases with increasing donor age. Fat tissue is available in large quantities in most patients and can be harvested easily with a minimally in-vasive approach (under either local or general anesthesia), offering a highly viable mesenchymal stem cells (MSC) population with optimal differentiation potential independ-ent of the donor’s age. The regenerative potential of adipose tissue-derived mesenchymal stem cells (MSC) is similar to that reported in other tissues (1).

The Lipogems® technologyThe Lipogems® technology, patented in 2010 and clinical-ly available since 2013 (PCT/IB2011/052204), represent a new completely closed tool to harvest, wash, process, and

reinject human (or animal) lipoaspirates. Briefly, the surgical procedure consists in two steps: the infiltration step, in which adrenalin, in a saline solution, and very diluted lidocaine are injected to induce vasoconstric-tion and local anesthesia, facilitating the subsequent lipoaspiration; the aspiration step, in which a standard liposuction technique is performed (2). In short, the Lipogems® technology is characterized by optimal han-dling ability and a great regenerative potential based on adipose-derived mesenchymal stem cells (MSC).

Lipogems® recently obtained FDA clearance. In this novel technology, the adipose tissue is washed, emulsi-fied, and rinsed and adipose cluster dimensions gradu-ally are reduced to about 0.3 to 0.8 mm. In the resulting Lipogems® product, pericytes are retained within an intact stromal vascular niche and are ready to interact with the recipient tissue after transplantation, thereby becoming mesenchymal stem cells (MSC) and starting the regenerative process. (1)

How is fat obtained

The fat used for the transfer can be taken from any area of the body, although the abdomen is preferred. Dilute local anaesthetic is injected into the donor area, than the fat is obtained using a special needle.

Mechanism of actionTheories related to the potential mechanism of ac-tion may include the micro-fragmented adipose tissue providing volume, support, cushioning, filling of soft tissue defects or potential healing and regenerative capabilities. Additional mechanisms may include di-rect differentiation and chondrogenesis, regenerative signaling by activated perivascular cells, tissue repair, signaling of trophic and paracrine factors, activation of opioid receptors, pain reduction, down-regulation of the arthrogenic muscle inhibition, exosome initi-ated cascades or a combination of all of these. In the resulting Lipogems® product, pericytes are retained within an intact stromal vascular niche and are ready to interact with the recipient tissue after transplanta-tion, thereby becoming MSCs and starting the regen-erative process (1).

Recent work on Ceserani indicate that Lipogems® micro-fragmented adipose tissue retains either per se, or in its embedded MSCs content, the capacity to induce vascular stabilization and to inhibit several macrophage functions involved in inflammation (3).

However, promising in vitro assays results (4) where the potential of intra-articular injection of micro-fragmented lipoaspirate was investigated, it may be speculated that an injectable autologous biologically-active scaffold (lipoaspirate), employed intra-articu-larly, may either:

1 - become a fibrous tissue that provides mechanical support for the load on the damaged cartilage;

2 - induce host chondrocytes to proliferate and produce ECM;

3 - provide cells at the site of injury, which could regenerate or repair the damaged or missing cartilage.