Stem Cells and Prolotherapy for Knee Osteoarthritis and Cartilage Regeneration
In this article Ross Hauser, MD discusses research that shows stem cell injection therapy will aid in the repair of osteoarthritic cartilage changes and relieve symptoms of stiffness, pain, disability, and inability to walk as commonly reported by our patients.
In new research, doctors from Australia published these observations about their patients suffering from knee osteoarthritis.
The problem: Current accepted medical treatment strategies for osteoarthritis are aimed at symptom control rather than curing or reversing the disease. Surgical options including knee replacement should be carefully examined before they are agreed to because of possibility of significant complications after the knee replacement.
The answer: There is a growing patient interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal stem cells (stem cells from soft tissue) in tissue repair.
Encouragingly, results of pre-clinical and clinical trials have provided initial evidence of efficacy and indicated safety in the therapeutic use of mesenchymal stem cell therapies for the treatment of knee osteoarthritis.1
In the Bone Marrow stem cell therapy procedure, bone marrow stem cells are drawn from the patient and injected into their knee with the hope of repairing cartilage and bone damage typical of knee osteoarthritis.
The non-surgical option is so appealing it is becoming a surgical option
Stem cells are so exciting that your surgeon may be anxiously waiting the ability and training to offer stem cell during surgery- here is the proof: Editorial – The Journal of Arthroscopic and Related Surgery a publication of the Arthroscopy Association of North America.
“we are believers in stem cell therapy” and “stem cells have substantial potential to allow 21st century physicians and surgeons… to achieve unprecedented tissue healing and repair.”2
More recently European researchers suggested to their arthroscopic surgeon readership:
- Nonsurgical treatments such as physiotherapy, anti-inflammatory medications, and other disease-modifying drugs all have modest and short-lasting effect.
- Biological approaches such as platelet concentrates (PRP), and mesenchymal adult stem cells are advocated amongst the most promising tool for the treatment of osteoarthritis, especially in the early phases when knee instability exists.
- (Stem cells and PRP) have showed promising results to relieve pain and reduce inflammation in patients with more advanced osteoarthritis as well, with the final aim to halt the progression of the disease and the need for joint replacement. 3
It has been long understood that there are limited treatment options for tissue restoration and the prevention of degenerative and osteoarthritic changes in the knee.
This is why stem cell therapy has generated so much excitement in the medical community. – it is the “unprecedented tissue healing and repair” as recent study proclaimed, and continued:
- Stem cell therapy is simpler than surgery
- Does not require hospitalization or surgery
- Provides pain relief
- and significantly improves cartilage quality.4
Which agrees with other studies and those cited above on the safety of stem cell injections, including this research on the ability of stem cells to promote meniscus regeneration following partial meniscectomy, and the positive effects of stem cells on osteoarthritic changes in the knee supporting the study of stem cells for knee-tissue regeneration.5
The educated patient will also find that not all research is favorable to stem cell therapy at this time due to “great deal of heterogeneity that is discrepancy in treatment methods,”6 the great variety of ways stem cell therapy is performed, some variations are not as potent as others, and the inability to come up with a gold standard platform to conduct clinical trials.
Seemingly the same issues that critics of our similar injection treatments of Prolotherapy and Platelet Rich Plasma Therapy point to. Variations in treatments and inability to conduct true controlled studies because of the nature of the treatment.7 Our article on Knee Osteoarthritis Injections explores the many different types of injections and the research.
One such variation is being led by researchers in China who have explored replacing apoptotic chondrocytes (dead or dying cartilage cells) in the cartilage by injecting mesenchymal stem cells. This effect was termed as bio-resurfacing.8
Stem Cell Injection Therapy For Knee Osteoarthritis
The tendons, muscles and ligaments of the knee are centered around the articular cartilage which is very important for flexibility and stabilization of the knee that allows it to bend and move freely about. This strong point of the joint too becomes its downfall. The loosening of ligaments is what brings about instability of the knee. This instability allows abnormal wear and tear on the cartilage, resulting in swelling of the joint and possibly overgrowth of the bone in attempt to stabilize the joint (this is known as osteoarthritis). Degeneration of or damage to this cartilage can lead to pain in the knee.
Can stem cell therapy regenerate meniscus and cartilage?
The latest scientific literature is telling us yes and that is why researchers and doctors are focusing on alternative methods for cartilage preservation and repair. Cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of cartilage, 9 and promoted meniscus regeneration.10 In a year long follow up animal study, doctors published research that stem cell treatments provided structural regenerations with mechanical properties comparable with the native cartilage.11,12,13
Can stem cell therapy stimulate natural hyaluronic acid production?
New research suggests that part of the healing process of stem cell therapy is the treatment’s ability to stimulate hyaluronic acid production. Hyaluronic Acid is the naturally occurring fluid in your knee that helps lubricate and cushion the joint. Hyaluronic acid injections have been widely used in osteoarthritis treatment.14
Two recent research studies examined the interactive roles of stem cells and naturally occurring hyaluronan (hyaluronic acid) in stimulating cartilage repair.
In the first study research doctors are saying that part of the healing mechanism of stem cell therapy is the treatment’s ability to stimulate hyaluronic acid production. They examined the interaction of Bone marrow mesenchymal stem cells and osteoarthritis-chondrocyte (cartilage cells) on the production of hyaluronan and inflammatory cytokines. Please see my article on Stem cell therapy and bone repair in osteoarthritis patients. In this article I explore the fascinating research on cell signalling and cytokines. Stem cells have the ability to reawaken dormant stem cells in a diseased joint.
The short conclusion is bone marrow mesenchymal stem cells change their behavior by increasing production of hyaluronan (hyaluronic acid) and decreasing inflammatory cytokines. 15
In the second study doctors exploring the use of Knee joint distraction (KJD) surgery found a “remarkable ‘spontaneous’ cartilage repair in which resident synovial fluid multipotential mesenchymal stromal cells (MSCs) may play a role. The stem cells from the knee environment. What they found was an underappreciated understanding of how the natural hyaluronic acid and stem cells rebuilt cartilage and how this provided a more rapid healing in surgical use.16
Stem cell injection therapy – use during surgery
Based on editorials and accompanying studies like those above, it is becoming more and more apparent that stem cell injection therapy will be the orthopedic treatment of choice for a new generation of orthopedists. Why the confidence in saying this? Because stem cell therapy is becoming thoroughly embraced by the surgical community. In this study’s abstract, doctor’s make an amazing statement.
“A new bone-marrow-derived mesenchymal stem cells technique has been developed for the treatment of osteochondral lesions of the knee. (Surgery!)
Thirty patients with osteochondral lesions underwent an arthroscopic one-step procedure. The bone marrow was harvested from the patients’ posterior iliac crest and arthroscopically implanted with a scaffold into the lesion site. . .Control MRI and bioptic samples showed an osteochondral regeneration of the lesion site. The one-step technique appears to be a good and reliable option for treatment of OLK at three years of follow-up.”17
Incredible. A new technique has been developed and it is surgery!
For the skeptic, can there be more compelling evidence of the confidence in stem cell therapy as a major tool in the regeneration of cartilage and damaged tissue than the need to develop proper surgical interventions?
“…most (surgical) approaches for delivering growth factors and stem cells have not been designed for dense connective tissues such as tendon. Therefore, we developed a scaffold capable of delivering growth factors and cells in a surgically manageable form for tendon repair.”18
In other words, in surgery they could not pinpoint the delivery of the growth factors. This may have lead to why surgeons developing injection techniques.
Writing in the medical journal titled Arthroscopy, researcher surgeons found that the results of their study showed: “intra-articular injection of infrapatellar fat pad-derived mesenchymal stem cells is effective for reducing pain and improving knee function in patients being treated for knee osteoarthritis.” 19 But a surgery was still involved, the stem cells from the kneecap area was harvested at the arthroscopic lateral portal site after the patient underwent arthroscopic debridement.
Stem Cell Therapy is, in our opinion, an alternative to surgery because most times the injections work better than the surgical introduction of stem cells.
In research published by the Journal of Bone and Joint Surgery, doctors have found that a single stem cell injection following meniscus knee surgery may provide knee pain relief and aid in meniscus regrowth. In this study, patients received a single injection of adult stem cells following the surgical removal of all or part of a torn meniscus. These patients reported a significant reduction in pain. Further, some meniscal tissue regrew! Up to 15 percent increase in meniscal volume at one year. There was no additional increase in meniscal volume at year two. (Comment: Maybe they should have given more than one injection.)
That question was seemingly answered in the American Academy of Orthopaedic Surgeons‘ press release. “The results of this study suggest that mesenchymal stem cells have the potential to improve the overall condition of the knee joint,” said Dr. Vangsness (a study author). “I am very excited and encouraged” by the results. With the success of a single injection, “It begs the question: What if we give a series of injections?”20
1 Freitag J, Bates D, Boyd R, et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy – a review.BMC Musculoskeletal Disorders. 2016;17:230. doi:10.1186/s12891-016-1085-9. [Pubmed]
2. Wetzler, Merrick J. Editorial Commentary: Doc, Can You Inject Stem Cells in My Knee? Arthroscopy , Volume 32 , Issue 1 , 110 [Pubmed]
3. de Girolamo L, Kon E, Filardo G, et al Regenerative approaches for the treatment of early OA. Knee Surg Sports Traumatol Arthrosc. 2016 Jun;24(6):1826-35. doi: 10.1007/s00167-016-4125-y. Epub 2016 Apr 27.
4. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentís J, Sánchez A, García-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013 Jun 27;95(12):1535-41. doi: 10.1097/TP.0b013e318291a2da. [Pubmed]
5. Vangsness CT Jr, Farr J 2nd, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M, et al. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014 Jan 15;96(2):90-8. doi: 10.2106/JBJS.M.00058. [Pubmed]
6. Wolfstadt JI, Cole BJ, Ogilvie-Harris DJ, Viswanathan S, Chahal J. Current concepts: the role of mesenchymal stem cells in the management of knee osteoarthritis. Sports Health. 2015 Jan;7(1):38-44. doi: 10.1177/1941738114529727. [Pubmed]
7. Uth K, Trifonov D. Stem cell application for osteoarthritis in the knee joint: A minireview. World J Stem Cells. 2014 Nov 26;6(5):629-36. doi: 10.4252/wjsc.v6.i5.629. [Pubmed]
8. Yang X, Zhu TY, Wen LC, Cao YP1, Liu C, Cui YP, Meng ZC, Liu H. Intraarticular Injection of Allogenic Mesenchymal Stem Cells has a Protective Role for the Osteoarthritis. Chin Med J (Engl). 2015 20th Sep;128(18):2516-2523. doi: 10.4103/0366-6999.164981. [Pubmed]
9. Mazor M, Lespessailles E, Coursier R, Daniellou R, Best TM, Toumi H. Mesenchymal stem-cell potential in cartilage repair: an update. J Cell Mol Med. 2014 Oct 29. doi: 10.1111/jcmm.12378. [Epub head of print]. [Pubmed]
10. Hatsushika D, Muneta T, Nakamura T, et al. Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model. Osteoarthritis Cartilage. 2014 May 2. pii: S1063-4584(14)01066-8. doi: 10.1016/j.joca.2014.04.028. [Epub ahead of print] [Pubmed]
11. Ude CC, et al. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model. PLoS One. 2014 Jun 9;9(6):e98770. doi: 10.1371/journal.pone.0098770. eCollection 2014. [Pubmed]
12.Ude CC, et al. Improved functional assessment of osteoarthritic knee joint after chondrogenically induced cell treatment. Osteoarthritis Cartilage. 2015 Aug;23(8):1294-306. doi: 10.1016/j.joca.2015.04.003. Epub 2015 Apr 14. [Pubmed]
13. Mehrabani D, Babazadeh M, Tanideh N, Zet al. The Healing Effect of Adipose-Derived Mesenchymal Stem Cells in Full-thickness Femoral Articular Cartilage Defects of Rabbit. Int J Organ Transplant Med. 2015;6(4):165-175. Epub 2015 Nov 1. [Pubmed]
14,15. Antonioli E, Piccinato CA, Nader HB, Cohen M, Goldberg AC, Ferretti M. Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes. Stem Cells Int. 2015;2015:640218. doi: 10.1155/2015/640218. Epub 2015 Jul 26. [Pubmed]
16. Baboolal TG, Mastbergen SC, Jones E, Calder SJ, Lafeber FP, McGonagle D. Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction. Ann Rheum Dis. 2015 May 6. pii: annrheumdis-2014-206847. doi: 10.1136/annrheumdis-2014-206847. [Epub ahead of print] [Pubmed]
17. Buda R, Vannini F, Cavallo M, Baldassarri M, Luciani D, Mazzotti A, Pungetti C, Olivieri A, Giannini S. One-step arthroscopic technique for the treatment of osteochondral lesions of the knee with bone-marrow-derived cells: three years results. Musculoskelet Surg. 2013 Feb 19. [Epub ahead of print] [Pubmed]
18. Manning CN, Schwartz AG, Liu W, Xie J, Havlioglu N, Sakiyama-Elbert SE, Silva MJ, Xia Y, Gelberman RH, Thomopoulos S. Acta Biomater. 2013 Feb 13. pii: S1742-7061(13)00065-2. doi: 10.1016/j.actbio.2013.02.008. [Epub ahead of print]
19. Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, Choi YJ.Mesenchymal Stem Cell Injections Improve Symptoms of Knee Osteoarthritis. Arthroscopy. 2013 Jan 29. pii: S0749-8063(12)01884-1. doi: 10.1016/j.arthro.2012.11.017. [Epub ahead of print].
20. Stem Cell therapy following Meniscal Surgery http://newsroom.aaos.org/media-resources/Press-releases/stem-cell-therapy-following-meniscus-knee-surgery-may-reduce-pain-restore-meniscus.htm
Page updated BW 7.10.2016