Vienna Stem Cell Center

VIENNA STEM CELL CENTER

Stem cell therapy—The future of osteoarthritis therapy

Dr. Christian Gäbler is one of Austria’s top international knee specialists. Together with his team of professionals, he leads the SPORTambulatorium Wien, a clinic specialized in acute and chronic joint conditions.

Dr. Gäbler's many years of activity and experience in the field of operative as well as conservative (non-surgical) treatment of joint problems are incorporated into all treatment approaches. The team at the Sportambulatorium Wien is committed to providing the most modern and effective therapy methods to all patients. Dr. Gäbler has many years of hands-on surgical and research experience with stem cell therapy.

The unprecedented possibilities that have opened up through the use of mesenchymal stem cells (which can be derived from fat cells) have led to the development of minimally invasive alternatives to the infiltration therapies and surgical procedures many are familiar with.

Recent studies have shown that stem cell therapy can significantly lower pain levels, thus improving quality of life, as well as increase cartilage thickness (see below).

The implantation of prosthetic joints, in particular for knees, can often be significantly delayed, and in some cases even prevented entirely, by using stem cell therapy treatments!

What are stem cells?

Stem cells are special human cells that have the unique ability to develop into many different cell and tissue types. This means that stem cells are able to heal virtually any tissue in the human body. This distinctive characteristic combines with the fact that they remain dormant until activated by encountering a problem (injury, inflammation, cell attrition) to make them highly interesting for medical applications. 

Once stem cells are activated, they begin to multiply and stimulate the body’s self-healing processes. 

What is the goal of stem cell therapy? 

• Achieving a symptom-free state 
• Restoring cartilage functionality
• Increasing resilience
• Improving patient quality of life 
• Avoiding prosthetic implantation 

How does stem cell therapy work? 

• In stem cell therapy (also called ACA therapy, or Autologue Conditioned Adipose Tissue Therapy), the body’s own cells activate and stimulate healing responses.
• Stem cells contain all the information necessary to differentiate and become other specialized cell types. They can therefore be used to treat all organs. Because some parts of the body are home to only a limited number of stem cells, supplemental cells are extracted from other very potent yet underused areas (from, for example, abdominal fat) and relocated where needed most.
• Recent scientific research has shown that stem cells can sense their environment and, if necessary, release high doses of bioactive molecules, antioxidants, and growth factors. This inhibits the inflammatory self-destructive processes that cause progressive degeneration in arthritic joints.
• It has also been shown that stem cells do something called “homing”, which is when the cells infiltrate cartilage defects and stimulate new cartilage growth right where it is needed most. This improves the resilience of the treated joint. 

For example, a scientific paper by S. Lopa et al. (2019) states: “Injective mesenchymal stem cell-based treatments for knee osteoarthritis: from mechanisms of action to current clinical evidence”, and describes the functional mechanism in more detail:

A dramatic cultural revolution started about 10 years ago when the scientists consistently focused their attention on the ability of these cells to “sense” the environment and secrete as a response large quantities of different bioactive molecules, such as cytokines, antioxidant and pro-angio- genic substances, trophic factors, and other proteins [45]. In physiological conditions, MSCs reside in the perivascular niche in a quiescent condition until the signals released after an injury activate their migration to the damaged site pro- moting the production of bioactive molecules to re-establish tissue homeostasis [46–48]. For this reason, they have been recently renamed as “medicinal signaling cells” [46, 47, 49]. As a result, the paracrine activity of MSCs would be involved in productive repair, by switching off inflammation, limiting stress response, and apoptosis, and recruiting the immune and reparative cells of the recipient [50–53]. 

An extensive in vitro and ex vivo research activity focused on the identification and explanation of the mechanisms of action of MSCs. Some of these studies clearly report an influence of MSC paracrine activity on inflammation and matrix turnover in OA, where the presence of a proinflammatory milieu was suggested as the switcher to promote the antiinflammatory effects of MSCs. Indeed, priming BMSCs with OA synovial fluid promotes an increase of indoleamine 2,3-dioxygenase (IDO) expression [54], while priming these cells with IFNγ and TNFα determines an increase of IDO activity and IL-6 expression [55]. Moreover, conditioned medium obtained from BMSCs primed with OA synovial fluid inhibits T-cell proliferation [54], while, after IFNγ and TNFα priming, BMSC-conditioned medium determines IL-1β downregulation and SOCS1 (suppressor of cytokine signaling) upregulation in synovium explants, and a down- regulation of ADAMTS5 and upregulation of IL-1Ra and SOCS1 in cartilage explants [55]. In addition, in the presence of high levels of pro-inflammatory mediators, a co-culture in transwell of ASCs obtained from infrapatellar fat pad, subcutaneous hip, or abdominal fat with chondrocytes and synoviocytes determines a decrease of IL-1β, IL-6, and CXCL8/IL-8 expression and release [56].

All these recent observations do not invalidate the “old school” theory based on the participation of MSCs to the repair process through their direct differentiation into tissue- specific cells. However, it is hard to believe that the few MSCs contained in a BMAC or SVF preparation injected intra-articularly can reach the multiple chondral lesions, permanently adhere and start the repair process by producing new cartilage. Therefore, while these two mechanisms of action of MSCs (paracrine action and direct cell differentiation) are not exclusive of each other, the difference is essential and needs to be taken into account for a critical analysis of the literature and for informing correctly the patients about the reasonable results they should expect from this kind of treatment.

Results

The majority of the studies reports significant improvements in terms of pain and knee function compared to baseline values, up to 24 months of follow-up.

What issues can be treated?

Stem cell therapy is considered the treatment of the future in orthopedics.
Currently, the following types of arthritis can be treated with success:

• Arthritis of the knee (gonarthrosis)
• Arthritis of the hip (coxarthrosis)
• Arthiritis of the shoulder
• Arthritis of the ankle

Success rates for stem cell therapy depend on a great number of factors. We here at the clinic are happy to provide more information and discuss your personal case in detail. 

How is stem cell therapy carried out? 

• Extraction of subcutaneous fatty tissue under local anesthesia
• Immediate preparation of the extracted tissue with specialized instruments. Using this method, we are able to obtain around 1,500,000 stem cells from the removed tissue.
• Cells are enriched with autologous blood (PRP), which contains high dosages of growth factors that augment the effects of the stem cells and make them more potent.
• The stem cell preparation is then infiltrated into the afflicted joint.
• Duration: 60 – 90 minutes.
• Following the procedure, the treated area must be protected from any stress for two weeks, sometimes by using crutches.

ATTENTION: Blood thinners must be discontinued three days prior to the treatment and their use must be reported to the doctor!

Advantages over other therapy methods: 

• minimally invasive
• rapid regeneration and thus a quick return to everyday life
• lower risk of infection than surgery
• rapid outpatient procedure lasts only 60 – 90 minutes 
• long-lasting impact 
• high success rates 
• minimal side effects (compared to knee replacement).
  

Stem cell therapy is currently one of the most promising osteoarthritic therapies. Please see the literature below for additional information. Research shows excellent results in wide range of cases. Stem cell therapy is in use worldwide, but is relatively new, so long-term studies are not yet available. We cannot make explicit promises about the exact healing outcomes of any therapy. 

Excerpts from over 500 published studies: 

• Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, Paterson K, Boyd R.: Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. In Regen Med. 2019 Mar;14(3):213-230.
• Lu L, Dai C, Zhang Z, Du H, Li S, Ye P, Fu Q, Zhang L, Wu X, Dong Y, Song Y, Zhao D, Pang Y, Bao C.: Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial. In: StemCell Res Ther. 2019 May 21;10(1):143.
• Ha CW, Park YB, Kim SH, Lee HJ.: Intra-articular Mesenchymal Stem Cells in Osteoarthritis of the Knee: A Systematic Review of Clinical Outcomes and Evidence of Cartilage Repair. In: Arthroscopy. 2019 Jan;35(1):277-288
• Dall’Oca C, Breda S, Elena N, Valentini R, Samaila EM, Magnan B. Mesenchymal Stem Cells injection in hip osteoarthritis: preliminary results. In Acta Biomed. 2019 Jan 10;90(1-S):75-80.
• Shimozono Y, Fortier LA, Brown D, Kennedy JG. Adipose-Based Therapies for Knee Pain-Fat or Fiction. In: J Knee Surg. 2019 Jan;32(1):55-64.
• Russo A, Screpis D, Di Donato SL, Bonetti S, Piovan G, Zorzi C. Autologous micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis: an update at 3 year follow-up. In: J Exp Orthop. 2018 Dec 19;5(1):52.
• Pers YM, Quentin J, Feirreira R, Espinoza F, Abdellaoui N, Erkilic N, Cren M, Dufourcq-Lopez E, Pullig O, Nöth U, Jorgensen C, Louis-Plence P. Injection of Adipose-Derived Stromal Cells in the Knee of Patients with Severe Osteoarthritis has a Systemic Effect and Promotes an Anti-Inflammatory Phenotype of Circulating Immune Cells. In: Theranostics. 2018 Nov 5;8(20):5519-5528.
• Baiguera, S., Jungebluth, Ph., Mazzanti, B., Macchiarini, P.Mesenchymal stromal cells for tissue-engineered tissue and organ replacements. In: Transpl Int 25. Nr. 4, April 2012, S. 369–382,
• Pretheeban, T., Lemos, D.R., Paylor, B. et al.: Role of stem/progenitor cells in reparative disorders. In: Fibrogenesis Tissue Repair 5. Artikelnr. 20, 27. Dezember 2012.
• Ra, J.C., Shin, I.S., Kim, S.H. et al.: Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. In: Stem Cells Dev 20. Nr. 8, August 2011, S. 1297–1308,
• Karp, J.M., Leng Teo, G.S.: Mesenchymal stem cell homing: the devil is in the details. In: Cell Stem Cell 4. Nr. 3, 6. März 2009, S. 206–216.
• Uccelli, A., Moretta, L., Pistoia, V.: Mesenchymal stem cells in health and disease. In: Nat Rev Immunol 8. Nr. 9, September 2008, S. 726–736.
• Chamberlain, G., Fox, J., Ashton, B., Middleton, J.: Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. In: Stem Cells 25. Nr. 11, November 2007, S. 2739–2749,
• Kern, S., Eichler, H., Stoeve, J. et al.: Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. In: Stem Cells 24. Nr. 5, Mai 2006, S. 1294–1301,