FRIDAY, 24 JANUARY 2020 | Nina Klein

Osteoarthritis Risk Factors

Osteoarthritis (OA) affects millions worldwide and while it is common among the elderly, people below 60 years can also be affected by the illness. People at risk include those who are overweight, those born with bone deficiencies, and those with a history of osteoarthritis in the family. If you have OA or have a family member who is suffering from this condition, then you may be familiar with some home remedies or medicines used to manage the pain. But did you know that there are alternative therapies that can address the root cause of osteoarthritis?

Unfortunately, we can’t prevent aging nor we can choose our genetic history, but we can lower the risk of osteoarthritis.

What is Osteoarthritis?

Simply put, it is a disease affecting the joints, characterized by stiffness and pain, especially during physical activities. It’s more common among older people, aged 60 and above. However, young people at risk could develop it as well. Risk factors include heredity, previous joint injury, and obesity. 

Types of Osteoarthritis

There are several kinds of osteoarthritis and they are divided according to causes and severity of the condition:

  • Primary - This is the type that’s most commonly diagnosed for people who are 55 to 60 years old. It is often associated with aging and the wear and tear of bones and joints.
  • Secondary - This has a specific cause that is not related to aging. An example is sustaining an injury or having this disease in the family. Obesity, hormone disorders, and lack of physical activities can also contribute to this because weak muscles cannot support the bones properly.
  • Severe - Though this is associated with an advanced stage of OA, it can also be referred to as a type of osteoarthritis. The reason for this is to distinguish the severe type of osteoarthritis from its milder or less serious form.
  • Erosive - Known to be an inflammatory type of OA, it mainly affects the joints of the hands. It is also a progressive disease, which means it can spread if not treated right away.
  • Known to be an inflammatory type of OA, it mainly affects the joints of the hands. It is also a progressive disease, which means it can spread if not treated right away.

Stages of Osteoarthritis

Osteoarthritis is a condition that can worsen if not detected or treated early.

  1. Stage 0 - Healthy knee and no signs of OA. Joints are functioning well.
  2. Stage 1 - Bone spurs along the edges appear. Simply explained, bone spurs make the edges of your bones ragged and they also narrow the spaces between bones.
  3. Stage 2 - Also considered as “mild” OA, there will be more severe bone spurs and there is slight discomfort when doing physical activities.
  4. Stage 3 - Known as moderate OA, the cartilage between the bones are damaged at this point. People suffering from this stage can experience stiffness around the joints and frequent pain when doing physical activities.
  5. Stage 4 - OA at this stage is severe and simple physical movements can cause great discomfort. Space between bones is very narrow and there is little to no cartilage left between the bones.

Symptoms of Osteoarthritis

OA shares many symptoms with other forms of arthritis. Because the tissues and muscles around the bones are affected, they could manifest in:

  • Joint pain after a day of physical activities
  • Joint stiffness that doesn’t go away, even after resting
  • Limited movement and muscle weakness
  • Bone cracking sounds after a sudden movement
  • Swelling of the joints

To confirm if these symptoms are caused by osteoarthritis or another type of arthritis, a blood test can be carried out.


What is the Difference Between Osteoporosis and OA?

Osteoporosis affects the thickness and strength of bones. This happens when the particles inside the bones become too thin which causes the bones to become fragile. Consequently, this often results in bones breaking easily. The illness can affect any bone in the body but, the usual parts affected are the spine, hips, and wrists.

Osteoarthritis vs. Rheumatoid Arthritis

Rheumatoid arthritis causes the inflammation of the joints. It can affect different parts of the body simultaneously. Parts of the body often affected are hands, wrists, and feet.
This may sound similar to osteoarthritis because they both result in pain and discomfort due to stiffness around the joints. However, treatment of patients differs because their causes are also distinct.
To be more specific, rheumatoid arthritis is an autoimmune condition while osteoarthritis is not. Autoimmune essentially means that your own immune system is attacking healthy cells because it confuses them for unhealthy ones.
On the other hand, osteoarthritis is brought about by several factors, including age, obesity, genetics, and birth defects.

Is Osteoarthritis Classified as a Disability?

Different countries have varying definitions of physical disability. What’s common among these definitions is that for a disease to be counted as a disability, it should prevent people from doing their day-to-day activities.
For example, the USA considers osteoarthritis as a disability if it impacts one’s ability to work. This allows patients to claim the Social Security Disability Benefits. In Canada, it is also listed under physical disabilities, making it possible for Canadians with osteoarthritis to claim Candian Disability Benefits.

Is it an Autoimmune Disease?

Osteoarthritis is not an autoimmune disease. This means that the weakening of joints and cartilages is not caused by the immune system attacking the healthy cells in these parts of the body.
There are several risk factors that lead to osteoarthritis such as age and weight. However, since these causes do not involve the immune system, osteoarthritis cannot be classified as an autoimmune disease.

Does Osteoarthritis run in Families?

According to studies published by the National Center for Biotechnology Information (NCBI), genetics play an important role in acquiring this disease. If OA runs in your family, the risk of having it later on in life is estimated to be between 35% to 65%.
Evidence-based studies published by the NCBI also state that the probabilities of inheriting OA for different parts of the body differ. For example, there is a 40% chance of getting OA in the knees while there is a 65% of inheriting OA in the hands and hips.
Because OA is a hereditary disease, scientists are keen to find out more about it by analyzing genomes and bio-bank data. If you do have family members suffering from osteoarthritis, try not to panic. It’s not a guarantee that you will get the disease, especially if you have an active and healthy lifestyle. Analyzing genomes and bio-bank data.

What are the Main Causes of Osteoarthritis?

Although scientists cannot target one main cause for this disease, there are several risk factors, including old age, excessive weight gain, injuries such as ligament damage, and genetics. Women are also more likely to develop osteoarthritis. In fact, out of the 27 million Americans with this disease, 60% are women. People born with conditions such as hip dysplasia or dislocation are also more likely to develop this disease later in their lives.

How is Osteoarthritis Diagnosed?

When you first visit the doctor, they can do a physical exam and check for swelling and redness around the joints. To confirm the onset of OA, they also need to do several tests:

  • Imaging Tests - Cartilage damage doesn’t appear on X-Ray images but the doctor can still see if bone space has narrowed, indicating the thinning of cartilage. Another imaging test is MRI or Magnetic Resonance Imaging. With this, a detailed image of bone and soft tissues is printed.
  • Laboratory Tests - Blood tests can be done to rule out other causes of the joint pain experienced by the client. Another test called joint fluid analysis can be used to examine the inflammation and rule out other causes like gout.
  • Genetic Tests - Though genetic testing doesn’t directly diagnose OA, it can show if one is at risk of inheriting the condition.

How do you Treat Osteoarthritis?

There are several ways to treat this disease, which include natural remedies, surgery, and physical therapy. Most of these are simply used to manage the pain and effects are not long lasting.
To address the root cause of osteoarthritis in the cellular level, evidence-based research papers suggest that stem cell therapy can hold the key in reversing its effects.

Natural Remedies

Home remedies for osteoarthritis are popular among people who experience mild or moderate pain. These methods include a change in lifestyle such as changing one’s diet and getting more exercise.

Proper Diet

Certain vegetables or food have been known to help alleviate the symptoms or reduce the pain. An example is green tea which has anti-inflammatory qualities. Another is ginger, which is said to decrease the pain and even the risk for disabilities linked to osteoarthritis. There are also food and drinks which should be avoided for people with this condition. Examples include artificial sweeteners, rice, bread, sugar, salt, trans fats, and alcohol.

Simple Exercises

Having OA shouldn’t stop people with this condition from living an active lifestyle. In fact, exercises such as yoga, tai chi, walking, and swimming can improve one’s flexibility. The Arthritis Foundation recommends around 150 minutes of these simple exercises per week.

Salt Bath

Taking a bath using Epsom salt may help relieve the pain for patients. This is because Epsom contains magnesium which alleviates the symptoms of inflammation.

Weight Support Devices

To shift one’s weight away from affected joints, devices can be used to support the movement of patients. They can be canes, knee braces, tools for grabbing or gripping, shoe inserts, and more.


Over-the-counter and prescription drugs are available for people suffering from chronic pain brought about by osteoarthritis. However, they only bring temporary relief and they shouldn’t be looked at as long-term solutions.

Pain Management Drugs

There are several prescription medications that can help patients who have osteoarthritis. An example is an acetaminophen like Tylenol which manages mild to moderate pain. Another is a duloxetine like Cymbalta, an antidepressant which also treats chronic pain.

Anti-Inflammatory Medication

Over-the-counter nonsteroidal drugs like ibuprofen usually relieve pain caused by osteoarthritis. These should be taken at recommended doses because it can have side effects such as liver damage and kidney problems.


Invasive procedures are available for osteoarthritis. Bear in mind that these operations can be risky and they are also not considered as long-term solutions.

Injections for Pain

This type of procedure requires the doctor to numb the area around the joint before inserting the injection filled with pain medication such as cortisone. Take note that taking pain medication surgically can worsen joint damage, so it's advisable to limit this procedure to a maximum number of four times every year.

Injections for Lubrication

There are also surgical procedures that offer more lubrication in the affected joints. An example is hyaluronic acid, a similar substance found in joint fluids that also offers pain relief. Injecting this into the knee can create a kind of liquid padding.

Joint Replacement Surgery

Also known as arthroplasty, this type of procedure requires a surgeon removing joint surfaces that are damaged. After which, they are replaced with metal or plastic parts which were specifically designed for the patient. The downside to this type of surgery is the risk of infection and even blood clot around the foreign parts inserted in the body. At the same time, these parts also need to be replaced every few years since they come loose or worn out.


This is done by examining the structure of the joint and removing damaged cartilage. Loose cartilage can also be repaired using this procedure.


In this operation, the surgeon tries to fix one side of the affected joint which was damaged by osteoarthritis. They do this by cutting or removing a part of the bone to shift the body weight away from the damaged part. This procedure is also called bone realignment surgery.

Motor Skills Therapy

Because OA patients have difficulty even with the simplest body movements, they need physical and occupational therapy to get on with their day-to-day activities.

Physical Therapy

Most physical therapists help people recovering from a serious injury or accident. These are the people who are relearning their motor functions like walking or lifting their arms. People suffering from osteoarthritis can also benefit from physical therapy since it involves exercises for the muscles that can reduce pain and increase one’s flexibility.

Occupational Therapy

Once you get back to your job or you’re capable enough of doing everyday tasks, an occupational therapist can help you settle in by finding a way to decrease stress on affected body parts. They train you with correct postures and recommend exercises that improve flexibility.

Stem Cell Therapy

Evidence-based studies suggest that stem cell-based therapies offer long-lasting effects for treating osteoarthritis. Stem cell therapy tries to address the problem on the cellular level by creating new cells and tissues to replace the damaged ones.

Can OA be Prevented?

Since OA develops with age, there are no guarantees that you can completely avoid it. What you can do instead is lessen the risk. Here’s what you can do to decrease your chances of getting osteoarthritis:

  • Maintain a healthy body weight to avoid putting stress on your joints. Stem cell-based treatments
  • Lower your blood sugar to avoid getting diabetes, which can lead to OA.
  • Be active and exercise to prevent your joints from getting stiff.
  • Be cautious and prevent your joints from getting injured. For example, wear knee pads and other protective gear while playing sports or working out.
  • Don’t ignore the pain. If you experience pain after exercising, make sure to rest to avoid overexertion and injury.

Can it be Reversed?

Most therapies simply address the symptoms but not the disease itself. Stem cell-based treatments can be considered a regenerative approach to the treatment of OA. This is because research has shown that stem cells are able to replenish lost nerve supply and transform into the cells that produce the cartilage. By having a new supply of cartilage, the effects can be more long-lasting compared to solutions that only suppress the symptoms.

Osteoarthritis Statistics and Research

There is an estimated 3.3% to 3.6% of people worldwide who suffer from OA. To put that into context, that means that it causes severe disability in 43 million people. According to the US National Institute of Health, it’s actually the 11th most paralyzing disease in the world.
In the United States alone, 80% of people over 65 years experience OA. And among these people, only 60% experience symptoms. This highlights the need for an annual check-up especially for people who are at risk - the elderly, people suffering from obesity, or those who have a genetic history of this disease.
Thankfully, there are ongoing studies about this condition. In 2015, the Arthritis Research UK together with the University of Oxford started clinical trials of the methotrexate drug that manages pain. In their pilot studies, they found that 37% of patients with knee OA who took this medicine felt a slight improvement in their condition.
According to the Osteoarthritis Treatment Market Analysis, the OA treatment market is expected to have a compounded annual growth rate of 4.2% from 2019 to 2024. This is largely because of the increasing elderly population who are most affected by this disease.
This market is biggest in North America due to the growing number of people with obesity. It’s no surprise that the overweight and elderly population in this region of the world are seeking new treatments and drugs to treat OA.
One of the therapies sought out by North Americans is stem cell therapy. Many clinics in the region are offering stem cell-based procedures but some have been called out by the US Food & Drug Administration Board due to ethical issues and non-compliance.
Outside North America, there are still clinics that offer stem cell therapy for osteoarthritis. Clinics in Europe like the ANOVA Institute for Regenerative Medicine are held to the strictest standards when it comes to quality and compliance, to ensure a safe treatment.

If you want to learn more about our treatment programs for people with osteoarthritis, feel free to reach out to us. 

  1. Georg Hansmann, Philippe Chouvarine, Franziska Diekmann, Martin Giera, Markus Ralser, Michael Mülleder, Constantin von Kaisenberg, Harald Bertram, Ekaterina Legchenko & Ralf Hass "Human umbilical cord mesenchymal stem cell-derived treatment of severe pulmonary arterial hypertension". Nature Cardiovascular Research volume 1, pages568–576 (2022).
  2. Murphy JM, Fink DJ, Hunziker EB, et al. Stem cell therapy in a caprine model of osteoarthritis . Arthritis Rheum. 2003;48:3464–74.
  3. Lee KB, Hui JH, Song IC, Ardany L, et al. Injectable mesenchymal stem cell therapy for large cartilage defects—a porcine model. Stem Cell. 2007;25:2964–71.
  4. Saw KY, Hussin P, Loke SC, et al. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: an experimental study in a goat model. Arthroscopy . 2009;25(12):1391–400.
  5. Black L, Gaynor J, Adams C, et al. Effect of intra-articular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Vet Ther. 2008;9:192-200.
  6. Centeno C, Busse D, Kisiday J, et al. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008;11(3):343–53.
  7. Centeno C, Kisiday J, Freeman M, et al. Partial regeneration of the human hip via autologous bone marrow nucleated cell transfer: a case study. Pain Physician. 2006;9:253–6.
  8. Centeno C, Schultz J, Cheever M. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell. 2011;5(1):81–93.
  9. Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose derived stem cells: a case series. J Med Case Rep. 2001;5:296.
  10. Kuroda R, Ishida K, et al. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage. 2007;15:226–31.
  11. Emadedin M, Aghdami N, Taghiyar L, et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15(7):422–8.
  12. Saw KY et al. Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy. 2013;29(4):684–94.
  13. Vangsness CT, Farr J, Boyd J, et al. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy. J Bone Joint Surg. 2014;96(2):90–8.
  14. Freitag, Julien, et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy–a review. BMC musculoskeletal disorders 17.1 (2016): 230.
  15. Maumus, Marie, Christian Jorgensen, and Danièle Noël. " Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: role of secretome and exosomes. " Biochimie 95.12 (2013): 2229-2234.
  16. Dostert, Gabriel, et al. " How do mesenchymal stem cells influence or are influenced by microenvironment through extracellular vesicles communication?. " Frontiers in Cell and Developmental Biology 5 (2017).
  17. Chaparro, Orlando, and Itali Linero. " Regenerative Medicine: A New Paradigm in Bone Regeneration. " (2016).
  18. Toh, Wei Seong, et al. " MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment. " Seminars in Cell & Developmental Biology. Academic Press, 2016.
  19. Chaparro, Orlando, and Itali Linero. " Regenerative Medicine: A New Paradigm in Bone Regeneration. " (2016).
  20. S. Koelling, J. Kruegel, M. Irmer, J.R. Path, B. Sadowski, X. Miro, et al., Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis , Cell Stem Cell 4 (2009) 324–335.
  21. B.A. Jones, M. Pei, Synovium-Derived stem cells: a tissue-Specific stem cell for cartilage engineering and regeneration , Tissue Eng. B: Rev. 18 (2012) 301–311.
  22. W. Ando, J.J. Kutcher, R. Krawetz, A. Sen, N. Nakamura, C.B. Frank, et al., Clonal analysis of synovial fluid stem cells to characterize and identify stable mesenchymal stromal cell/mesenchymal progenitor cell phenotypes in a porcine model: a cell source with enhanced commitment to the chondrogenic lineage, Cytotherapy 16 (2014) 776–788.
  23. K.B.L. Lee, J.H.P. Hui, I.C. Song, L. Ardany, E.H. Lee, Injectable mesenchymal stem cell therapy for large cartilage defects—a porcine model, Stem Cells 25 (2007) 2964–2971.
  24. W.-L. Fu, C.-Y. Zhou, J.-K. Yu, A new source of mesenchymal stem cells for articular cartilage repair: mSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model , Am. J. Sports Med. 42 (2014) 592–601.
  25. X. Xie, Y. Wang, C. Zhao, S. Guo, S. Liu, W. Jia, et al., Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration , Biomaterials 33 (2012) 7008–7018.
  26. E.-R. Chiang, H.-L. Ma, J.-P. Wang, C.-L. Liu, T.-H. Chen, S.-C. Hung, Allogeneic mesenchymal stem cells in combination with hyaluronic acid for the treatment of osteoarthritis in rabbits , PLoS One 11 (2016) e0149835.
  27. H. Nejadnik, J.H. Hui, E.P. Feng Choong, B.-C. Tai, E.H. Lee, Autologous bone marrow–derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study , Am. J. Sports Med. 38 (2010) 1110–1116.
  28. I. Sekiya, T. Muneta, M. Horie, H. Koga, Arthroscopic transplantation of synovial stem cells improves clinical outcomes in knees with cartilage defects , Clin. Orthop. Rel. Res. 473 (2015) 2316–2326.
  29. Y.S. Kim, Y.J. Choi, Y.G. Koh, Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes , Am. J. Sports Med. 43 (2015) 2293–2301.
  30. W.-L. Fu, Y.-F. Ao, X.-Y. Ke, Z.-Z. Zheng, X. Gong, D. Jiang, et al., Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment , Knee 21 (2014) 609–612.
  31. Y.-G. Koh, O.-R. Kwon, Y.-S. Kim, Y.-J. Choi, D.-H. Tak, Adipose-derived mesenchymal stem cells with microfracture versus microfracture alone: 2-year follow-up of a prospective randomized trial , Arthrosc. J. Arthrosc. Relat. Surg. 32 (2016) 97–109.
  32. T.S. de Windt, L.A. Vonk, I.C.M. Slaper-Cortenbach, M.P.H. van den Broek, R. Nizak, M.H.P. van Rijen, et al., Allogeneic mesenchymal stem cells stimulate cartilage regeneration and are safe for single-Stage cartilage repair in humans upon mixture with recycled autologous chondrons , Stem Cells (2016) (n/a-n/a).
  33. L. da Silva Meirelles, A.M. Fontes, D.T. Covas, A.I. Caplan, Mechanisms involved in the therapeutic properties of mesenchymal stem cells , Cytokine Growth Factor Rev. 20 (2009) 419–427.
  34. W.S. Toh, C.B. Foldager, M. Pei, J.H.P. Hui, Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration , Stem Cell Rev. Rep. 10 (2014) 686–696.
  35. R.C. Lai, F. Arslan, M.M. Lee, N.S.K. Sze, A. Choo, T.S. Chen, et al., Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury , Stem Cell Res. 4 (2010) 214–222.
  36. S. Zhang, W.C. Chu, R.C. Lai, S.K. Lim, J.H.P. Hui, W.S. Toh, Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration, Osteoarthr . Cartil. 24 (2016) 2135–2140.
  37. S. Zhang, W. Chu, R. Lai, J. Hui, E. Lee, S. Lim, et al., 21 – human mesenchymal stem cell-derived exosomes promote orderly cartilage regeneration in an immunocompetent rat osteochondral defect model , Cytotherapy 18 (2016) S13.
  38. C.T. Lim, X. Ren, M.H. Afizah, S. Tarigan-Panjaitan, Z. Yang, Y. Wu, et al., Repair of osteochondral defects with rehydrated freeze-dried oligo[poly(ethylene glycol) fumarate] hydrogels seeded with bone marrow mesenchymal stem cells in a porcine model
  39. A. Gobbi, G. Karnatzikos, S.R. Sankineani, One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee , Am. J. Sports Med. 42 (2014) 648–657.
  40. A. Gobbi, C. Scotti, G. Karnatzikos, A. Mudhigere, M. Castro, G.M. Peretti, One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years , Knee Surg. Sports Traumatol. Arthrosc. (2016) 1–8.
  41. A. Gobbi, G. Karnatzikos, C. Scotti, V. Mahajan, L. Mazzucco, B. Grigolo, One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2-Year follow-up , Cartilage 2 (2011) 286–299.
  42. K.L. Wong, K.B.L. Lee, B.C. Tai, P. Law, E.H. Lee, J.H.P. Hui, Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up , Arthrosc. J. Arthrosc. Relat. Surg. 29 (2013) 2020–2028.
  43. J.M. Hare, J.E. Fishman, G. Gerstenblith, et al., Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the poseidon randomized trial, JAMA 308 (2012) 2369–2379.
  44. L. Wu, J.C.H. Leijten, N. Georgi, J.N. Post, C.A. van Blitterswijk, M. Karperien, Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation , Tissue Eng. A 17 (2011) 1425–1436.
  45. L. Wu, H.-J. Prins, M.N. Helder, C.A. van Blitterswijk, M. Karperien, Trophic effects of mesenchymal stem cells in chondrocyte Co-Cultures are independent of culture conditions and cell sources , Tissue Eng. A 18 (2012) 1542–1551.
  46. S.K. Sze, D.P.V. de Kleijn, R.C. Lai, E. Khia Way Tan, H. Zhao, K.S. Yeo, et al., Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells , Mol. Cell. Proteomics 6 (2007) 1680–1689.
  47. M.B. Murphy, K. Moncivais, A.I. Caplan, Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine , Exp. Mol. Med. 45 (2013) e54.
  48. M.J. Lee, J. Kim, M.Y. Kim, Y.-S. Bae, S.H. Ryu, T.G. Lee, et al., Proteomic analysis of tumor necrosis factor--induced secretome of human adipose tissue-derived mesenchymal stem cells , J. Proteome Res. 9 (2010) 1754–1762.
  49. S. Bruno, C. Grange, M.C. Deregibus, R.A. Calogero, S. Saviozzi, F. Collino, et al., Mesenchymal stem cell-derived microvesicles protect against acute tubular injury, J. Am. Soc. Nephrol. 20 (2009) 1053–1067.
  50. M. Yá˜nez-Mó, P.R.-M. Siljander, Z. Andreu, A.B. Zavec, F.E. Borràs, E.I. Buzas, et al. Biological properties of extracellular vesicles and their physiological functions (2015).
  51. C. Lawson, J.M. Vicencio, D.M. Yellon, S.M. Davidson, Microvesicles and exosomes: new players in metabolic and cardiovascular disease , J. Endocrinol. 228 (2016) R57–R71.
  52. A.G. Thompson, E. Gray, S.M. Heman-Ackah, I. Mager, K. Talbot, S.E. Andaloussi, et al., Extracellular vesicles in neurodegenerative diseas—pathogenesis to biomarkers, Nat. Rev. Neurol. 12 (2016) 346–357.
  53. I.E.M. Bank, L. Timmers, C.M. Gijsberts, Y.-N. Zhang, A. Mosterd, J.-W. Wang, et al., The diagnostic and prognostic potential of plasma extracellular vesicles for cardiovascular disease , Expert Rev. Mol. Diagn. 15 (2015) 1577–1588.
  54. T. Kato, S. Miyaki, H. Ishitobi, Y. Nakamura, T. Nakasa, M.K. Lotz, et al., Exosomes from IL-1 stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes , Arthritis. Res. Ther. 16 (2014) 1–11.
  55. R.W.Y. Yeo, S.K. Lim, Exosomes and their therapeutic applications, in: C. Gunther, A. Hauser, R. Huss (Eds.), Advances in Pharmaceutical Cell TherapyPrinciples of Cell-Based Biopharmaceuticals, World Scientific, Singapore, 2015, pp. 477–491.
  56. X. Qi, J. Zhang, H. Yuan, Z. Xu, Q. Li, X. Niu, et al., Exosomes secreted by human-Induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats , Int. J. Biol. Sci. 12 (2016) 836–849.
  57. R.C. Lai, F. Arslan, S.S. Tan, B. Tan, A. Choo, M.M. Lee, et al., Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles , J. Mol. Cell. Cardiol. 48 (2010) 1215–1224.
  58. Y. Zhou, H. Xu, W. Xu, B. Wang, H. Wu, Y. Tao, et al., Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro , Stem Cell Res. Ther. 4 (2013) 1–13.
  59. Y. Qin, L. Wang, Z. Gao, G. Chen, C. Zhang, Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo , Sci. Rep. 6 (2016) 21961.
  60. M. Nakano, K. Nagaishi, N. Konari, Y. Saito, T. Chikenji, Y. Mizue, et al., Bone marrow-derived mesenchymal stem cells improve diabetes-induced cognitive impairment by exosome transfer into damaged neurons and astrocytes , Sci. Rep. 6 (2016) 24805.
  61. K. Nagaishi, Y. Mizue, T. Chikenji, M. Otani, M. Nakano, N. Konari, et al., Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes , Sci. Rep. 6 (2016) 34842.
  62. S.R. Baglio, K. Rooijers, D. Koppers-Lalic, F.J. Verweij, M. Pérez Lanzón, N. Zini, et al., Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species , Stem Cell Res. Ther. 6 (2015) 1–20.
  63. T. Chen, R. Yeo, F. Arslan, Y. Yin, S. Tan, Efficiency of exosome production correlates inversely with the developmental maturity of MSC donor, J. Stem Cell Res. Ther. 3 (2013) 2.
  64. R.C. Lai, S.S. Tan, B.J. Teh, S.K. Sze, F. Arslan, D.P. de Kleijn, et al., Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome , Int. J. Proteomics 2012 (2012) 971907.
  65. T.S. Chen, R.C. Lai, M.M. Lee, A.B.H. Choo, C.N. Lee, S.K. Lim, Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs , Nucleic Acids Res. 38 (2010) 215–224.
  66. R.W. Yeo, R.C. Lai, K.H. Tan, S.K. Lim, Exosome: a novel and safer therapeutic refinement of mesenchymal stem cell, J. Circ. Biomark. 1 (2013) 7.
  67. R.C. Lai, R.W. Yeo, S.K. Lim, Mesenchymal stem cell exosomes, Semin. Cell Dev. Biol. 40 (2015) 82–88.
  68. B. Zhang, R.W. Yeo, K.H. Tan, S.K. Lim, Focus on extracellular vesicles: therapeutic potential of stem cell-derived extracellular vesicles , Int. J. Mol. Sci. 17 (2016) 174.
  69. Hu G-w, Q. Li, X. Niu, B. Hu, J. Liu, Zhou S-m, et al., Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice , Stem Cell Res. Ther. 6 (2015) 1–15.
  70. J. Zhang, J. Guan, X. Niu, G. Hu, S. Guo, Q. Li, et al., Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis , J. Transl. Med. 13 (2015) 1–14.
  71. B. Zhang, M. Wang, A. Gong, X. Zhang, X. Wu, Y. Zhu, et al., HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing, Stem Cells 33 (2015) 2158–2168.
  72. B. Zhang, Y. Yin, R.C. Lai, S.S. Tan, A.B.H. Choo, S.K. Lim, Mesenchymal stem cells secrete immunologically active exosomes , Stem Cells Dev. 23 (2013) 1233–1244.
  73. C.Y. Tan, R.C. Lai, W. Wong, Y.Y. Dan, S.-K. Lim, H.K. Ho, Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models , Stem Cell Res. Ther. 5 (2014) 1–14.
  74. C. Lee, S.A. Mitsialis, M. Aslam, S.H. Vitali, E. Vergadi, G. Konstantinou, et al., Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension , Circulation 126 (2012) 2601–2611.
  75. B. Yu, H. Shao, C. Su, Y. Jiang, X. Chen, L. Bai, et al., Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1 , Sci. Rep. 6 (2016) 34562.
  76. Jo CH, Lee YG, Shin WH, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof of concept clinical trial. Stem Cells. 2014;32(5):1254–66.
  77. Vega, Aurelio, et al. Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation. 2015;99(8):1681–90.
  78. Davatchi F, Sadeghi-Abdollahi B, Mohyeddin M, et al. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011;14(2):211–5
  79. Hernigou P, Flouzat Lachaniette CH, Delambre J, et al. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case- controlled study. Int Orthop. 2014;38(9):1811–1818
  80. Galli D, Vitale M, Vaccarezza M. Bone marrow-derived mesenchymal cell differentiation toward myogenic lineages: facts and perspectives. Biomed Res Int. 2014;2014:6.
  81. Beitzel K, Solovyova O, Cote MP, et al. The future role of mesenchymal Stem cells in The management of shoulder disorders . Arthroscopy. 2013;29(10):1702–1711.
  82. Isaac C, Gharaibeh B, Witt M, Wright VJ, Huard J. Biologic approaches to enhance rotator cuff healing after injury. J Shoulder Elbow Surg. 2012;21(2):181–190.
  83. Malda, Jos, et al. " Extracellular vesicles [mdash] new tool for joint repair and regeneration. " Nature Reviews Rheumatology (2016).

  1. Xu, Ming, et al. " Transplanted senescent cells induce an osteoarthritis-like condition in mice. " The Journals of Gerontology Series A: Biological Sciences and Medical Sciences (2016): glw154.
  2. McCulloch, Kendal, Gary J. Litherland, and Taranjit Singh Rai. " Cellular senescence in osteoarthritis pathology ." Aging Cell (2017).

Patient Services at ANOVA Institute for Regenerative Medicine

  • Located in the center of Germany, quick access by car or train from anywhere in Europe
  • Simple access worldwide, less than 20 minutes from Frankfurt Airport
  • Individualized therapy with state-of-the-art stem cell products
  • Individually planned diagnostic work-up which include world-class MRI and CT scans
  • German high quality standard on safety and quality assurance
  • Personal service with friendly, dedicated Patient Care Managers
  • Scientific collaborations with academic institutions to assure you the latest regenerative medical programs