Lipogems – Application of Mesenchymal Stem Cells Therapy

Mechanism of action

Theories related to the potential mechanism of action 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 direct 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 initiated 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 transplantation, thereby becoming MSCs and starting the regenerative 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-articularly, 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.

Lipogems® Clinical Application

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.

The very low infection risk is a result of the production of the antimicrobial molecule LL-37 (1). 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. In addition, single-case reports have demonstrated that intra-articular injection 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 improvement 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 Cuore-Don Calabria Hospital, Verona, Italy recently reported results on 170 patients affected by knee chondropathy 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 significant improvement. Out of 170 patients they reported only two adverse events (abdominal hematoma).

Professor Joseph Purita, Director of the Institute of Regenerative 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 Lipogems® 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 application. Our data suggesting that the use of adipose derived mesenchymal stromal/stem cells (Ad-MSC) therapy 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.

Literature:

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.

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