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Simple Combination Therapy May Heal Rotator Cuff Tears

Edward G. Loniewski, DO, FACOS, FAOAO

Rotator cuff tears affect over 22% of the normal population and this percentage climbs to over 36% in patients in their 80’s according to one study published in the Journal of Orthopedics. The scary fact found in this study that up to 2/3rds of the patients above the age of 60 had no symptoms of the tear! Thus, we can see that rotator cuff problems are very common as we age and most of us will never know if we ever have this problem until our shoulders become painful and dysfunctional at a later date.

The rotator cuff is a group of four major muscles coming together to help “rotate” the shoulder joint. The true cause of rotator cuff tears can be multifactorial meaning that there are many reasons we cannot account for the disease. However, some researchers have found a common thread in biopsies performed at the area of the tear. There seems to be a link between a decrease in stem cells around where the tear happens. Repairing the tear and supplementing the repair with stem cells helps the repair process and prevent retearing according to another study. Although, there are only a few studies on this subject, there appears to be a link between the lack of cells and disease and the replacement of these cells and success.

A new technique combining hyaluronic acid and platelet rich plasma named enhanced PRP may provide this same type of results without a major surgery or the extended cost of stem cell therapy. Hyaluronic acid has been used for numerous medical conditions such as cataracts, skin wrinkles and arthritis for over 20 years. In orthopedics we have used this under the trade names Orthovisc, Monovisc or Supartz with about 50-60% of patients responding positively with knee arthritis. Although the mechanisms of action are many, a simplified explanation is that this cushions and lubricates the joint. However, not only does it cushion and lubricate, it is a natural carrier or substrate for growth factors. Hyaluronic acid provides an optimal environment for cells to live and thrive. However, it lacks the essential growth factors found in our body for the repair of damaged tissue. Luckily, platelet rich plasma contains numerous growth factors including Platelet Derived Growth Factor (PDGH) and Vascular Endothelial Growth Factor (VEGF). These are released fairly quickly when injected into an area of damage and they are lost within the bloodstream. However, when they are injected with a hydrogel such as hyaluronic acid, they can be slowly released in the area of damage over a longer period of time. This slow release, coupled by the fact that hyaluronic acid acts as a scaffold for tissue healing provides an optimal environment for the treatment of small to midsize rotator cuff tears. Not only is this a theoretical treatment, but one which was tested in a double blinded, placebo controlled study.

Patients were split into 4 groups of about 50 patients into each group. All the patients had a partial tear of the rotator cuff. One group received normal saline as a placebo, Group 2 received Hyaluronic Acid ( HA), Group 3 received PRP and Group 4 received the combination of PRP + HA. Patients were followed closely with follow up visits at 1,3,6 and 12 months and a repeat MRI. Patients were asked to complete two surveys ( the Constant Score and the American Shoulder and Elbow Surgeon). The PRP and the PRP+HA groups improved. The PRP + HA group improved the pain and function ASES score by 40.82 points and the PRP group improved by 27.02 while the HA group only improved 11.34 points and the Saline group worsened by 1.21 points. The Constant score confirmed these findings with an improvement of the PRP+HA group by 33.19 pts. The PRP group improved by 23.73 pts and the HA group by 12.93 pts. However, surprisingly the MRI scoring of the size and retraction of the rotator cuff also improved. In the combination therapy group, the score improved 5.85 pts; the PRP group also had an improvement of 2.89 pts and the HA group only improved 0.41 pt. However, the saline group worsened by 2 pts. What this data shows is that not only does the combination of HA and PRP provide far superior clinical results with reduction of pain and increased function of the shoulder, but it also demonstrates healing of the partial rotator cuff tears.

The best part of this treatment is the value for patients. The cost of this combination therapy for shoulders is about $1050 which is much lower than the cost of many PRP injections and certainly lower than stem cell therapies and surgical repair. In addition, the complication rates of these injections is very low. At Cellular Healing, we provide nearly painless injections with the additional use of nitrous oxide (laughing gas) anesthetic. There are no major restrictions after these injections and you can return to work or play the next day. The only drawback is the fact that you may need to have this repeated every 1-2 years. Thus, you could argue that the combination treatment of HA and PRP is one of the best values in orthopedic medicine.

You can call 810-299-8552  for a personal one-on one consultation or you can click HERE to schedule on-line.

References: 

[1] Minagawa H, Yamamoto N, Abe H, et al. Prevalence of symptomatic and asymptomatic rotator cuff tears in the general population: From mass-screening in one village. J Orthop. 2013;10(1):8–12. Published 2013 Feb 26. doi:10.1016/j.jor.2013.01.008

[1] Hernigou P, Merouse G, Duffiet P, Chevalier N, Rouard H. Reduced levels of mesenchymal stem cells at the tendon-bone interface tuberosity in patients with symptomatic rotator cuff tear. Int Orthop. 2015 Jun;39(6):1219-25. doi: 10.1007/s00264-015-2724-8. Epub 2015 Mar 12. PubMed [citation] PMID: 25757411

[1] Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H. 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 Sep;38(9):1811-8. doi: 10.1007/s00264-014-2391-1. Epub 2014 Jun 7. PubMed [citation] PMID: 24913770

[1] Cai YU, Sun Z, Liao B, Song Z, Xiao T, Zhu P. Sodium Hyaluronate and Platelet-Rich Plasma for Partial-Thickness Rotator Cuff Tears. Med Sci Sports Exerc. 2019;51(2):227–233. doi:10.1249/MSS.0000000000001781

Combination of a Joint Lubricant and Natural Growth Factors May Be The Best Since Peanut Butter & Chocolate?

By: Edward G. Loniewski, DO, FACOS, FAOAO  

Peanut Butter Meets Chocolate vintage commercial

Remember the ads for Reese's Peanut Butter Cups?   When peanut butter collided with chocolate and a match made in heaven was born.  That image came up again when I started to read the studies on the combination of platelet rich plasma with hyaluronic acid and I thought again “a match made in heaven.”   

Hyaluronic Acid Restores Natural Lubrication

Hyaluronic Acid is a natural lubricant and anti-inflammatory covered by most insurances

Hyaluronic Acid (HA) was FDA approval for the treatment of osteoarthritis of the knee since the 1990’s.   The major mechanisms of actions are proposed to restore the normal viscosity (thickness) of the joint fluid and the reduction of inflammatory products produced by an osteoarthritic joint.    Interestingly enough, hyaluronic acid can be formed into many different shapes as a scaffold for three dimensional  mesenchymal stem cell growth. The problem with hyaluronic acid treatments in the past has been the low response rate.  Only 50 to 60% of the patients receiving hyaluronic injections in the knee have a positive response.   This has lead some organizations such as the American Academy of Orthopedic Surgeons (AAOS) to rescind its initial recommendation of this treatment for arthritis.   ( see references)

Platelet Rich Plasma Restores Natural Balance

PRP provides your own natural growth factors to help restore balance

Platelet Rich Plasma (PRP) has also been used in orthopedics since the 1990’s but mainly to enhance procedures using large bone grafts.  Recently, this has been expanded to treat common tendon and joint problems with some  success.   The mechanisms of action of PRP are also numerous, but two main proposed actions include reduction of harmful biochemicals as well as the delivery of important growth factors necessary for joint hemostasis (the balance between damage and repair with each of our joints).   Since, PRP is made from the host (you), it is not considered a drug and thus, does not need FDA approval.  Numerous studies have been conducted comparing PRP to HA and although both provide positive benefits, PRP has been shown to have  wider response in a greater number of patients over a longer period of time.   Yet, there are still failures of both treatments.   This led researchers to ponder the thought of combining HA with PRP to see if there is synergistic effect. (see references)

Combining PRP and HA Complement Each Other

Basic research into the possibility of combining the positive benefits of restoring the natural thickness and function of the joint fluid with the growth factor benefits of platelet rich plasma led to the proposal of a three armed study comparing HA, PRP and the combination therapy of PRP and HA.  In addition, a sequence of basic science studies proposed numerous positive mechanisms of action to reduce proinflammatory chemical production; protection of the cartilage and meniscus; as well as reducing the production of osteoarthritis immune cells.  Thus, scientists followed these recommendations and designed a few studies on human knee osteoarthritis to see if these proposals are true.

Researchers in China have performed controlled studies examining the clinical effects of combining hyaluronic acid and platelet rich plasma for two very common orthopedic conditions, namely arthritis of the knee and partial rotator cuff tears of the shoulder.  Both studies had positive results. ( see references)

Combining the natural lubricant with natural growth factors shows promise for knees and shoulders

  HA and PRP Combo Provides Superior Results for Knee Arthritis

In the knee arthritis study, researchers conducted a double blinded, placebo controlled study over a 52 week period.  This is one of the most powerful methods to determine if a treatment is equal to or superior to another treatment. Both the patients and the researchers are blinded, or unable to know which treatment each patient received.  Patients either received a placebo ( a saline injection) , hyaluronic acid, PRP or a combination of PRP and hyaluronic acid injection. At the end of the study, the patients receiving the hyaluronic acid injections alone had an average increase in function and a decrease in pain by 10.9 points through a very standard method of measurement called the Western Ontario & McMaster Universities Arthritis Index abbreviated WOMAC .   The PRP patients had an increase of 15.9 points, but the combination of hyaluronic acid and PRP had an amazing increase of 23.7 points!  Thus, combining the two may provide superior relief for over a year period.   If we compare this to some studies on knee replacement, the average improvement after a year is about 24 points.   Although, this is not a direct comparison study and it is hard to compare the two results, it does give us some baseline information for future studies. (see references)  

HA and PRP Mixture Helps Repair Rotator Cuff Tears of the Shoulder  

In the shoulder study, patients were split into 4 groups of about 50 patients into each group.  All the patients had a partial tear of the rotator cuff which is a common condition causing pain and weakness of the shoulder.   One group received normal saline as a placebo, Group 2 received Hyaluronic Acid ( HA), Group 3 received PRP and Group 4 received the combination of PRP + HA.  Again, patients were followed closely with follow up visits at 1,3,6 and 12 months and a repeat MRI. Patients were asked to complete two surveys ( the Constant Score and the American Shoulder and Elbow Surgeon).   As expected, the PRP and the PRP+HA groups improved. The PRP + HA group improved the pain and function ASES score by 40.82 points and the PRP group improved by 27.02  while the HA group only improved 11.34 points and the Saline group worsened by 1.21 points.   The Constant score confirmed these findings with an improvement of the PRP+HA group by 33.19 pts.  The PRP group improved by 23.73 pts and the HA group by 12.93 pts. However, surprisingly the MRI scoring of the size and retraction of the rotator cuff  also improved. In the combination therapy group, the score improved 5.85 pts; the PRP group also had an improvement of 2.89 pts and the HA group only improved 0.41 pt.  However, the saline group worsened by 2 pts. What this data shows is that not only does the combination of HA and PRP provide far superior clinical results with reduction of pain and increased function of the shoulder, but it also demonstrates healing of the partial rotator cuff tears. (see reference list)

Thus, we can see a developing pattern of superior results not only in the knee, but also in the shoulder with very similar results at one year.  This confirmed by patient surveys and now also by MRI evidence.

The best part of this treatment is the value for patients.  A good portion of this treatment is covered by most (but not all) insurance carriers for knee arthritis.   Medicare and many major carriers cover the hyaluronic acid injections and a standard PRP injection is only $500 for each joint.  Thus, you could have very good pain relief for less than the cost of two new tires or many round trip airfares.   There are very limited complications and side effects from these treatments, and the only drawback is the fact that you may need to have this repeated every 1-2 years.   Compare this to a joint replacement costing over $35,000 and more than $4,000 out of pocket expenses as wells as a complication rate of anywhere from 3% to 16% and more than 6 weeks away from work or recreation.  Most of these injections require no time off work and the complication rates are very low.   Many of the current treatments for either knee arthritis or rotator cuff tears have very high costs; long periods of time away from work or physical activity and have higher rates of complications.  Thus, you could argue that the combination treatment of HA and PRP is one of the best values in orthopedic medicine.       

Could the combination of Hyaluronic Acid and Platelet Rich Plasma be the best idea since peanut butter combined with chocolate?   As the announcer would say…”only time will tell.”

If you are interested in consultation and discussing your joint concerns with a board certified orthopedic surgeon, call 810-299-8552 or register online HERE.

Dr. Edward G. Loniewski, Brighton, Michigan

About the Author:  Dr. Edward G. Loniewski, DO, FACOS, FAOAO is a board certified orthopedic surgeon specializing in adult arthritis.  He is fellowship trained and has extensive experience in alternative therapies for treating arthritis including over 4,000 cell based treatments since 2005.   He has been featured on the Outdoor Channel as well as WXYZ TV. local news channel and has over 60 informational videos through CellularHealing.net.    He is recognized as an expert in cell therapy as a frequent speaker at national and international conferences.  Dr. Loniewski has developed instrumentation and cell therapy techniques used by physicians all over the world. He is also founder of a not for profit organization which provides cell therapy to the underprivileged as well as trains the physicians of tomorrow on the proper use of cell therapies.   He has offices in Brighton, Michigan and provides one on one consultation to personalize a comprehensive program tailored to your specific goals easily fit within your social  and professional commitments. Register for a SEMINAR or for a CONSULTATION.   “Remember, these are your cells for your healing.”

References:

The effect of sodium hyaluronate treating knee osteoarthritis on synovial fluid interleukin -1β and clinical treatment mechanism. Yang L, Zhang J, Wang G.Pak J Pharm Sci. 2015 Jan;28(1 Suppl):407-10. PubMed [citation]  PMID:25631505

Chiou CS, Wu CM, Dubey NK, et al. Mechanistic insight into hyaluronic acid and platelet-rich plasma-mediated anti-inflammatory and anti-apoptotic activities in osteoarthritic mice. Aging (Albany NY). 2018;10(12):4152-4165.

Altman RD, Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. Hyalgan Study Group. J Rheumatology. 1998 Nov; 25(11):2203-12

Oryan A, Alidadi S, Moshiri A. Platelet-rich plasma for bone healing and regeneration. Expert Opin Biol Ther. 2016;16(2):213-32. doi: 10.1517/14712598.2016.1118458. Epub 2015 Dec 4. Review.

Filardo G, Di Matteo B, Kon E, Merli G, Marcacci M., Platelet-rich plasma in tendon-related disorders: results and indications.  Knee Surg Sports Traumatol Arthrosc. 2018 Jul;26(7):1984-1999. doi: 10.1007/s00167-016-4261-4. Epub 2016 Sep 24. Review.


Chen CPC1Cheng CH2Hsu CC3Lin HC1Tsai YR1Chen JL4. The influence of platelet rich plasma on synovial fluid volumes, protein concentrations, and severity of pain in patients with knee osteoarthritis. Exp Gerontol. 2017 Jul;93:68-72. doi: 10.1016/j.exger.2017.04.004. Epub 2017 Apr 20.

https://www.fda.gov/media/124138/download

anchanatawan W1Arirachakaran A2Chaijenkij K3Prasathaporn N4Boonard M5Piyapittayanun P2Kongtharvonskul J6.  Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee.  Knee Surg Sports Traumatol Arthrosc. 2016 May;24(5):1665-77. doi: 10.1007/s00167-015-3784-4. Epub 2015 Sep 19.

Andia I, Abate M.,  Knee osteoarthritis: hyaluronic acid, platelet-rich plasma or both in association? Expert Opin Biol Ther. 2014 May;14(5):635-49. doi: 10.1517/14712598.2014.889677. Epub 2014 Feb 17. Review.PubMed [citation] PMID: 24533435

Chen WH, Lo WC, Hsu WC, Wei HJ, Liu HY, Lee CH, Tina Chen SY, Shieh YH, Williams DF, Deng WP., Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy. Biomaterials. 2014 Dec;35(36):9599-607. doi: 10.1016/j.biomaterials.2014.07.058. Epub 2014 Aug 28.  PubMed [citation] PMID: 25176059

Yu W, Xu P, Huang G, Liu L. Clinical therapy of hyaluronic acid combined with platelet-rich plasma for the treatment of knee osteoarthritis. Exp Ther Med. 2018;16(3):2119-2125.

Courtney, PM et al. Complications Following Outpatient Total Joint Arthroplasty:  An Analysis of a National Database. J Arthroplasty, 2016 Dec 14

https://health.costhelper.com/knee-replacement.html#extres3


Are Stem Cells Better Than Most Common Treatments for Knee Pain?

Some of the most convincing evidence for the use of stem cell therapy exists for arthritis of the knee. While we can’t comment much on the use of stem cells for arthritis in other joints, each joint manifests unique results in our clinical practice, with knees showing particularly beneficial outcomes.

What’s the Evidence Stem Cells work for knee arthritis?
First, let us look at literature which illustrates a series of cases as a “proof of concept” type of study. Dr. Chris Centeno developed a method of using bone marrow derived stem cells through his patented and marketed Regenexx™ stem cell clinics, which are based in Colorado. Dr. Centeno published his findings from his patient registry evaluations, wherein he looked at 373 patients who received this treatment in the form of an injection into the osteoarthritic knee. He examined these patients at one, three, and six month intervals, as well as once a year. Over this period of time, Dr. Centeno found that all his patients showed improvements in pain and function, and that the severity of the arthritis did not have an impact on the outcome.There is, however, a problem with such a study: it does not compare the treatment in question against another form of treatment, allowing us to determine which treatment may be a better choice.

Stem Cells Better than Hyaluronic Injections (Chicken Fat)
If we now compare the results of bone marrow derived stem cells to commonly accepted non-surgical treatments for osteoarthritis of the knee, we can start to evaluate which treatment is superior.

Spanish researchers performed such a study when they compared cultured bone marrow stem cells to a commonly treatment called Hyaluronic Acid (sometimes known in the United States as rooster injections or chicken fat injections to the knee). Hyaluronic injections are a very common form of treatment in the United States; over 4 million of these injections are given each year, and it is a commonly accepted and covered treatment by many health insurance carriers. These Spanish researchers compared a form of cultured bone marrow stem cells taken from a separate individual, and injected it into the knee of patients. Another group received the standard single injection of hyaluronic injection. Both sets of patients were followed for a year, being monitored with surveys and an MRI.

At the end of one year, the stem cell recipient patients showed significantly lower pain scores and higher functionality scores. In addition, the group that received the stem cell treatment had improved MRI findings.

Stem Cells Better than Arthroscopy and Micro-fracture.
If we compare bone marrow derived cells to commonly accepted surgical treatments for arthritis, we also find some interesting results. One common surgical treatment used to treat isolated areas of arthritis of the knee is to debride, scrape, or puncture holes in the areas where there is exposed bone. (This action can only be done in patients who have good cartilage surrounding the worn area.) These techniques were made very popular for professional athletes suffering from high impact trauma. The original form of this surgery was developed in Okemos, Michigan by Dr. Lanny Johnson, who invented most of our modern arthroscopic procedures.

The procedure was further promoted by Dr. Steadman at the famous Vail Clinic. This updated procedure poked or drilled small holes within the exposed bone in hopes that this would allow stem cells from the bone of the knee to fill in the space, stimulating healing. This method is currently known as a micro-fracture technique. However, this procedure involved a degree of pain, as the small breaks require the patient to maintain a very strict adherence to limited weight bearing.

Dr. Koh from South Korea’s Center for Stem Cell and Arthritis Research decided to compare the results of stem cells taken from fat and fixed with a special type of fibrin glue to a micro-fractured area of the knee, and compare this to a standard microfracture technique. He followed over 40 patients in each group for over two years. During this time, he not only compared their MRI’s, but also was able to perform a visual arthroscopic examination and biopsy of most of the participants in the study - 57 of the 80 patient, to be exact. Dr. Koh and his research group discovered that patients who received the stem cells and micro-fracture had statically significant improvement in their pain scores (36 vs. 30-point improvement), as well as improved MRI findings, with 65% of the patients in the stem cell group showing complete cartilage coverage vs. 45% in the non-stem cell group.  Note that this study used cultured, fat-derived stem cells, and therefore results should be viewed with caution, particularly when being compared to bone marrow.

Dr. Lisa Fortier from Cornell, a veterinary physician, performed a series of studies evaluating the use of the same type of bone marrow we use for knees and its effect on horses. One interesting study of her’s evaluated using a simple injection of bone marrow concentrate versus performing the microfracture surgery in horses. Dr. Fortier and her team followed the horses with sequential MRI studies after one year, and discovered that the bone marrow group had improved findings in the area of the bone next to the injury, as well as the tissue textures.

Stem Cells Better than Most Surgeries for Knee Arthritis
Another commonly used treatment for arthritis is called a high tibial osteotomy, abbreviated HTO. This procedure corrects the bow of the knee joint and helps to restore it to natural alignment. During the procedure, the shin or femur bone is cut and moved over to correct the bow. Dr. Wong and his research team in Singapore evaluated the effects of cultured (grown) stem cells on improving the outcome of this surgery for osteoarthritic knees. Fifty-six patients were randomly assigned to receive stem cells and hyaluronic injection, while others were given the hyaluronic injection alone three weeks after their corrective bone procedure. Both groups were followed for over two years, with follow-up MRI’s performed at the one year mark. In the end, the patients who received the cultured stem cells had improved pain and function scores, as well as improved MRI findings. A follow up study conducted in Italy found similar positive results.

Researchers in Singapore performed another study evaluating if surgery is even necessary for cartilage defects of the knee. The very first cartilage cell procedure approved by the FDA was named Autologous Chondrocyte Implantation (ACI). Surgeons would harvest, or sample, some cartilage from a patient during the patient’s first surgery. This sample would then be sent to a company in Boston, where the team would culture and expand only the cartilage cells. Afterward, the cells would be shipped back to the surgeon; a second surgery would be performed upon which the patient’s knee is opened up and a pouch is made from the covering of the shin bone, then glued to create a small pouch where the cultured cells are injected.

This process would require two surgeries and prolonged sessions of physical therapy. Because of this, the researchers proposed they simply inject stem cells rather than requiring the patient to undergo two prolonged surgeries.

Seventy-two patients were placed into one of two test groups. The first group comprised of thirty-six patients, and all received the two stage ACI surgery. The second group consisted of thirty-six patients as well, and all received a single injection of bone marrow derived stem cells. Both groups of patients were then followed for two years. Both groups showed significant improvements in outcome; however, the two stage ACI surgery group did not show improvement if the patient was above the age of 45, while age made no difference for the stem cell injection group.

Researchers in Jabalpur, India were curious if they could improve the results of a very common surgery used to treat arthritic knees with mechanical symptoms such as meniscus tears (cartilage ring tears). Arthroscopy is a minimally invasive procedure using a mini fiber optic camera to look within the knee and treat common conditions such as a tear or loose pieces of cartilage. The researchers divided fifty patients into two groups. Group A received the standard arthroscopic procedure and group B received the arthroscopic procedure, but also received some bone marrow derived stem cells. The stem cell group B had improved quality of life as well as reduced pain.

What???? Stem Cells are Better than Knee Replacement!!!
Now, what about comparing stem cell therapy to one of our best-known treatments for arthritis of the knee - knee replacement surgery? Knee replacement surgery is a very reliable and durable method of relieving the pain and dysfunction of arthritis; in fact, the American Academy of Hip and Knee Surgeons (AAHKS) reports that over 90% of patients have relief of pain and over 80% of these patients have the same joint replacement in place over 20 years from the time of their surgery.

Although 90% of patients experience pain relief, this does not quantify the degree of the pain relief - for example, most patients may receive pain relief, but a portion of this 90% may only receive ten to twenty percent reduction of their pain, which is not satisfactory. Because of this, we must look at the whole group of joint replacement patients. When we look at this whole group, we find that twenty-seven to thirty percent of the patients are dissatisfied with this joint replacement. These findings were also discussed in a review article by researchers at Bristol University, UK.

Dr. Loniewski has personally replaced over 5,000 joints in his career, and can confirm that this is a good option for patients who have severe deformity of the knee. However, the knee replacement procedure does has some concerns. The first is the potential complication rates.

A review of over 160,000 patients through a national database by researchers from Rush University in Chicago found that the 30-day complication rate form both hip and knee replacement was 16%. Patients over the age of 70 or with histories of malnutrition, diabetes, cardiac disease, and smoking had higher risks.

Other than the higher complication rate, potential patients should consider the inconvenience of a joint replacement surgery. Although some joint replacements can be done in a minimally invasive manner and some patients can have this done as an outpatient, there is still the simple fact that the knee is maximally manipulated with the cutting of bone and the release of ligaments, as well as the implantation of foreign metal and plastic. For this reason, even with our modern minimally invasive techniques, patients still require 24/7 around-the-clock care for a minimum of two weeks; most require three weeks.

Following surgery, patients cannot drive their cars, shop, or enjoy a night out while the knee heals. They are recommended to attend physical therapy at least twice a week for a minimum of three weeks. You the patient cannot return to work (even sedentary types of work) for these same three weeks, and any moderate or high demand types of work (food service, factory) must be put on hold for up to three months. There is also the need for narcotic medications as well as medications to prevent blood clots.

Finally, these procedures normally only treat one knee at a time, meaning patients may have to repeat the treatment within the same year.

Phillipe Hernigou, MD from the University of Paris recognized the shortcomings of joint replacement as well as the benefits of bone marrow derived stem cell therapy and decided to compare the two treatments in some well-designed long term studies. He first looked at using this treatment for young patients who traditionally required joint replacement for a devastating type of arthritis of the knee called avascular necrosis - a condition where the blood supply to the bone around the knee is diminished, and the result is death of the bone and cartilage.

This condition normally occurs in younger patients during the third and fourth decades of life. The thought of replacing a knee in such a young group is concerning since most joint replacements have a limited life expectancy, while younger patients will likely have multiple joint surgeries in the future. His research team decided to evaluate the use of autologous bone marrow derived stem cell therapy injected into the diseased bone near the joint to treat this condition and compare it to traditional joint replacement in the same patient. Thirty patients with an average age of twenty-eight were randomized to receive a stem cell replacement to one knee and a joint replacement to the other knee.

The randomization process eliminated bias in selecting the less severe knee for one specific treatment. All the patients were followed for an amazing twelve years of average follow up. MRI’s were performed prior to the surgery and again at 24 months, five years, and at the last follow-up visit. X-rays were also reviewed and compared to the initial study. Samples of bone marrow were taken at specific sites in the arthritic knee as well as the pelvis where the bone marrow was harvested. The surgical procedure to replace the knee took an average 1.5 times longer than the entire stem cell procedure on the other knee.

After the surgery, patients reported a higher rate of blood clots on the side which received the knee replacement (15% vs. 0%). At the last follow up, six of the thirty knees (20%) with the knee replacement required another surgery, while only three of the stem cell knees (10%) required a knee replacement - but at longer periods out of six, eight and twelve years from the stem cell procedure. The patients recorded their satisfaction with each knee.

The knee replacement group showed eight of thirty (26%) reporting excellent pain relief, and the stem cell side reported four of thirty (13.3%); but there were a much higher number of patients in the poor pain relief after the knee replacement, with four out of thirty (13.3%) and only one out of thirty (3%) from the stem cell side. Most importantly, however, is that when patients were asked to point to the knee they preferred more, 70% of patients pointed to the stem cell side!

When Dr. Hernigou evaluated the sequential MRIs of the stem cell treated knee, he found that there was an increase in cartilage volume as well as a significant decrease in the size of the bone marrow lesion (BML), which is an area of inflamed bone and a cause of pain. Even when some of the stem cell knees required a joint replacement, sampling of the bone and cartilage revealed that the patients who had a poor response still had an average 45% increase in bone mass and required a less invasive type of knee replacement than the other side. In addition, none of the stem cell knees that required a knee replacement required further surgeries.

Dr. Hernigou’s team also looked at treating the very elderly with the same treatment. This study comprised of sixty elderly male patients all 85 years old or older. Group A was treated with the standard total knee replacement for both knees., while Group B was treated with the bone marrow stem cells to both knees injected directly into the bony part of the knee next to the joint. Group C had one knee injected with the stem cells, and the other knee replaced.   After an average of six years (ranging from two to fifteen years), the patients in Group B (stem cell group) showed the following:

  • Improved knee function scores (Knee Society Scores). There was a 16.3-point improvement for the stem cell group versus only an 8.9-point improvement for total knee group.
  • Faster functional recovery-   At 9 months, the stem cell group had faster recovery than the total knee group.
  • Lower complication rates. Blood clots occurred in only 2% of the stem cell group compared to 12% in the knee replacement group. None of the stem cell patients required a blood transfusion, and 29.3% of the total knee group required blood transfusions.
  • Higher use of analgesic medications such as narcotics were used in the total knee group.
  • Lower re-operation rate. Only one of the stem cell patients required further surgery or conversion to a total knee. However, 5% of the total knee patients required further surgery.
  • Higher overall satisfaction. In Group C, when patients were asked to point to the knee which they preferred, 70% of the patients pointed to the stem cell therapy knee.

It is very interesting that Dr. Hernigou has been able to demonstrate that cell based treatments help the two most vulnerable populations affected by arthritis of the knee. Both the very young and the very old may benefit from this treatment with superior safety, efficiency and patient satisfaction.

Here is what we learned today:  Stem Cell Therapy for Knees Have Proof that they have superior results to:

  • Hyaluronic Injections (chicken fat)
  • Autologous Cellular Implantation (cartilage cell implant)
  • Corrective surgery (High Tibial Osteotomy)
  • Arthroscopy
  • Total Knee Replacement
  • Not only is this therapy superior in results to the most commonly used treatments, it is safer and less expensive.

If you would like a face to face consultation with Dr. Loniewski to discuss your knee pain and the options available, please call 810-299-8552 for an appointment.

Footnotes
1 - Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A Systematic Review and Meta-Analysis of Clinical Trials. Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ, Canadian Critical Care Trials Group. PLoS ONE. 2012 Oct 25; 7(10): e47559 PMC [article] PMCID: PMC3485008 PMID: 23133515 DOI: 10.1371/journal.pone.0047559

2 - Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. Hernigou P, Homma Y, Flouzat-Lachaniette CH, Poignard A, Chevallier N, Rouard H. J Bone Joint Surg Am. 2013 Dec 18;95(24):2215-21. doi: 10.2106/JBJS.M.00261. PubMed [citation] PMID:24352775

3 - A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis. Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. BMC Musculoskeletal Disorders. 2015 Sep 18; 16: 258 PMC [article]

4 - Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial. Vega A, Martín-Ferrero MA, Del Canto F, Alberca M, García V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sánchez A, García-Sancho J.
Transplantation. 2015 Aug;99(8):1681-90. doi: 10.1097/TP.0000000000000678. PMID: 25822648

5 - Adipose-Derived Mesenchymal Stem Cells With Microfracture Versus Microfracture Alone: 2-Year Follow-up of a Prospective Randomized Trial. Koh YG, Kwon OR, Kim YS, Choi YJ, Tak DH. Arthroscopy. 2016 Jan;32(1):97-109. doi: 10.1016/j.arthro.2015.09.010. Epub 2015 Nov 14. PMID:26585585

6 - Minimally Manipulated Bone Marrow Concentrate Compared with Microfracture Treatment of Full-Thickness Chondral Defects: A One-Year Study in an Equine Model. Chu CR, Fortier LA, Williams A, Payne KA, McCarrel TM, Bowers ME, Jaramillo D. J Bone Joint Surg Am. 2018 Jan 17;100(2):138-146. doi: 10.2106/JBJS.17.00132. PMID: 29342064

7 - 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. Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH. Arthroscopy. 2013 Dec;29(12):2020-8. doi: 10.1016/j.arthro.2013.09.074. PubMed [citation] PMID:24286801

8 - Combination of High Tibial Osteotomy and Autologous Bone Marrow Derived Cell Implantation in Early Osteoarthritis of Knee: A Preliminary Study. Cavallo M, Sayyed-Hosseinian SH, Parma A, Buda R, Mosca M, Giannini S. Archives of Bone and Joint Surgery. 2018 Mar; 6(2): 112-118 PMC [article]PMCID: PMC5867354 PMID:29600263

9 - Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH. Am J Sports Med. 2010 Jun;38(6):1110-6. doi: 10.1177/0363546509359067. Epub 2010 Apr 14. PubMed [citation] PMID: 20392971

10 - The new avenues in the management of osteo-arthritis of knee--stem cells. Varma HS, Dadarya B, Vidyarthi A. J Indian Med Assoc. 2010 Sep;108(9):583-5. PubMed [citation] PMID:21510531

11 - A review of the clinical approach to persistent pain following total hip replacement. Lam YF, Chan PK, Fu H, Yan CH, Chiu KY.
Hong Kong Med J. 2016 Dec;22(6):600-7. Epub 2016 Oct 31. Review. PubMed [citation]
PMID: 27795449

12 - Total knee replacement: is it really an effective procedure for all?
Wylde V, Dieppe P, Hewlett S, Learmonth ID. Knee. 2007 Dec;14(6):417-23. Epub 2007 Jun 26. Review. PubMed [citation] PMID: 17596949

13 - Complications Following Outpatient Total Joint Arthroplasty: An Analysis of a National Database.
Courtney PM, Boniello AJ, Berger RA. J Arthroplasty. 2017 May;32(5):1426-1430. doi: 10.1016/j.arth.2016.11.055. Epub 2016 Dec 14. PubMed [citation] PMID: 28034481

14 - Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee.
Hernigou P, Auregan JC, Dubory A, Flouzat-Lachaniette CH, Chevallier N, Rouard H.
Int Orthop. 2018 Mar 27. doi: 10.1007/s00264-018-3916-9. PubMed [citation] PMID: 29589086

15 - Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Hernigou P, Homma Y, Flouzat Lachaniette CH, Poignard A, Allain J, Chevallier N, Rouard H. Int Orthop. 2013 Nov;37(11):2279-87. doi: 10.1007/s00264-013-2017-z. Epub 2013 Jul 24.PubMed [citation] PMID: 23881064 PMCID: PMC382489

16 - Autologous conditioned serum for the treatment of osteoarthritis and other possible applications in musculoskeletal disorders. Frizziero A, Giannotti E, Oliva F, Masiero S, Maffulli N. Br Med Bull. 2013;105:169-84. doi: 10.1093/bmb/lds016. Epub 2012 Jul 4. Review. PubMed [citation]PMID:22763153

17 - Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee. Hernigou P, Auregan JC, Dubory A, Flouzat-Lachaniette CH, Chevallier N, Rouard H. Int Orthop. 2018 Mar 27. doi: 10.1007/s00264-018-3916-9. [Epub ahead of print] PubMed [citation] PMID: 29589086

How Do Stem Cells Work?

How Do Stem Cells Work?

By: Edward G. Loniewski, DO, FACOS, FAOAO

This is a very common question asked not only by our patients, but also many educated physicians using this therapy.   After years and years of trying to understand this process myself, I have attempted to simplify this very complex and complicated system down to 3 easy to remember mechanisms.   The problem with simplifying a complex system is that it can leave out some other minor systems at work, but if we want to take a 10,000 foot look at this mountain of information, I believe that you can begin to make more sense of this process by boiling this down to a few basic mechanisms.   The goal is not to make anyone an expert, but rather just an informed consumer so you can make an educated and knowledgeable decision if this therapy may be a viable treatment for either yourself or your loved ones.    Many great philosophers in the past such as Camus, Kierkegaard and Aristotle have suggested we narrow down complex systems into three reasons, examples or theories because it allowed the student to understand the subject in a coherent manner.  Thus, I am following their suggestion to narrow this down to 3 main mechanisms.  But I think a more important reason is that I can’t remember more than three things at a time!

 

Before we talk about stem cells, we need to clarify that common stem cell therapies used in the United States contain a very small number of stem cells. Many treatment centers may only transfer a few thousand cells and thus, the mechanisms of action of these treatments are not due solely to the stem cells.  Rather, they are due to the other nurturing biochemical compounds found around these cells.  Therefore, bone marrow is  very important in this process.  Bone marrow is the natural home environment for stem cells in your body.  This is where they are born, raised and utilized.  Thus, we need to consider the contributions of the bone marrow products surrounding the stem cells such as Interleukin 1-B receptor antagonist (that was a mouthful) and Alpha 2 Macroglobulin as well as Transforming Growth Factor- Beta.  These are important to help set the proper environment for stem cells to conduct their work.   So, the title of this section is a bit misleading and should say “How does Cell Therapy Work?”

So, what are these three mechanisms of action?  They are very easy to remember since they all start with R.   This is what we call a pneumonic because they sound similar and are easier to remember.   These mechanisms are:

  • Reduce
  • Restore
  • Regenerate

We will take each one and explain how this mechanism relates to cell based therapies.

Reduce-  Cell based therapies reduce the harmful biochemical storm in your joint.   We normally have nice balance of specific biochemicals in our joints.  They serve to help maintain the normal cell function of the joint.   However, as we age, or with trauma or with specific inflammatory diseases of the joint, this chemical balance is upset and we have too many pro-inflammatory chemicals causing continued destruction.  One of the most important biochemical families are the interleukins and especially interleukin-1-beta.  This is normally used to help regulate our response to infection or inflammation.  However, the production of this biochemical begins to rise and cause widespread inflammation and destruction of both cartilage and bone.   Interleukin 1-B is the “Kingpin” or “Godfather” of these biochemicals and REDUCING IL-1 B will help restore this normal balance.  Many biochemical pathways lead back to Interleukin-1 B and just like the Corleone family, when we start to investigate who is causing all this crime and destruction, many pathways lead back to the “Godfather” biochemical.  Interleukin-1B controls the judges, the newspapers, and the police in New York City just like Don Corleone. 

 

 

How is this done? Our own bone marrow contains a natural inhibitor of IL-1 B called Interleukin 1-B receptor antagonist.  This is the antidote for the toxic effects of IL-1B and it is found intimately wrapped in the environment of your stem cells throughout your bone marrow.   When we take your own bone marrow, there is a nice concentration of this natural inhibitor already present and connected to your stem cells. Race horses have used Interleukin 1-B Receptor Antagonist for the past 12 years to treat arthritis and improve their performance.   In fact, this therapy is so effective and popular, one horses in the 2017 Kentucky Derby was named IRAP which stands for the IL-1 B receptor antagonist.   As humans, you only require a small amount of interleukin-1 B receptor antagonist in a ratio of 100:1 for it to be effective in REDUCING its activity.

Thus, Bone Marrow Concentrate taken from your own pelvis can REDUCE the biochemical storm happening in your joint naturally and effectively.  Without this reduction, there is little hope that any cartilage cells will survive and continued destruction will occur.

Our next mechanism involves Restoring the normal cell to cell communication of a joint.

Your joint is an organ just like a kidney, brain or heart.   An organ is a group of specialized cells working together to perform a specific function.   For example, your kidney cells function together to filter out toxins in your blood and help maintain healthy blood pressure. Your joint has specific cells designed to allow smooth and efficient movement of your body.   To accomplish this goal, the specialized cells need to talk to one another through a special communication mechanism for one cell to talk to another local cell.  This is called paracrine signaling.    A diseased joint has a dysfunction of this signaling due to guess who….”The Godfather.”   In a normal joint, cartilage cells need to talk to other cartilage cells to help with their normal function. Bone cells need to talk to other bone cells to do the same.  When Interleukin 1-B is elevated, tunneling through the diseased bone next to your joint occurs and bone cells start to talk to cartilage cells rather than other bone cells through a mechanism called “cross talk”.

 

This cross talk is just like someone trying to give you directions to a restaurant when everyone else is talking very loudly in the background.  Both parties on the line become frustrated and eventually hang up.  Your bone and cartilage cells do the same and become dysfunctional unable to perform the specialized functions they were born to do because they cannot communicate effectively with each other.  The bone marrow concentration helps RESTORE this normal cell to cell signaling by reducing the Interleukin-1 B and shutting down the tunnels between bone and cartilage.  Over time, the small tunnels are shut down and cartilage cells now talk only to cartilage cells so they can function like a normal organ.   Normal tissue function returns which in turn RESTORES the normal function of the joint as an organ.

Finally, we can discuss Regenerate as the third, but least important mechanism of cell therapy.    Although many so called stem cell clinics  claim the regenerative properties of their therapy is the most important mechanism, as we can see from the two previous mechanisms, unless you have a stable environment first, there is no reason to regenerate any tissue because it will be either destroyed by the biochemical storm caused by the Godfather or if by some miracle, there is tissue growth, the cells won’t be able to function as a normal organ because of the loss of paracrine signaling or cell to cell communication.    So, cell based therapies REDUCE this biochemical imbalance and RESTORE normal cell to cell communication setting the stage for proper REGENERATION.

Think about this process compared to another very common disease in our country.  Alcoholism is very prevalent in our society.  I don’t really need to remind anyone of it’s prevalence.  Ironically, just about the same number of people in the United States are affected by Arthritis as Alcoholism which is about 28 million.   If we look at one of the most effective treatments for alcoholism, we can see a parallel to the three mechanisms of cell based therapies.  Alcohol recovery programs normally begin with the removal of the harmful chemicals, or alcohol, causing the problem.    In cell based therapies, we remove the harmful biochemical causing continued destruction.  Without the removal of alcohol, the destructive process continues and this is the same for your joint.   Next, critical relationships are restored through personal, family and marriage counseling.  During counseling, broken lines of communication are restored.

In cell based therapy, broken and dysfunctional cell to cell communication is restored.   Once the harmful chemical has been REDUCED and the communication RESTORED, now the family can thrive and function again and grow in a stable, non-toxic and loving environment.  Your joint is the same with the REDUCED toxic chemicals and in a stable RESTORED environment promoting the REGENERATION of new tissue.   The amount of new tissue may be very small in relation to the dramatic effects of reducing the toxins and restoring the normal function of the cells, but it is still a property of the mesenchymal stem cells delivered in the bone marrow concentrate.  There is little relationship between the amount of tissue regenerated and the relief of your pain.  However, there is a direct and linear relationship between levels of Interleukin-1 beta and the severity of your arthritic symptoms.   Thus, reducing this harmful biochemical is paramount to the restoration and regeneration of your joint.

To prove this point, think of the last time you took a pill for your arthritis pain. Not everyone responds to these pills, but most people have some relief for a brief period of time after taking such a medication.   Pills such as Aleve or Motrin have absolutely no effect on regenerating new cartilage tissue. Yet, you may have experienced some relief for about 4 to 6 hrs.   Have you ever wondered how this happened?   From a biochemical perspective, this medication reduced one of the biochemical pathways causing pain in your joint.   Yet, this is pill in your stomach and not in your joint and it did not regenerate any new tissue and may have contributed to some further tissue destruction, but it provided some relief!    Bone marrow concentrate stem cell therapy provides long term REDUCTION of the most important “Godfather” biochemical pathways for years and it RESTORES normal cell to cell communication leading to an optimal environment for the icing on the cake which is REGENERATION of some tissue.

I hope this simple explanation has accomplished its goal of making you a more informed and educated consumer and hopefully you can now understand if this therapy may be helpful for your our your loved one’s joint.   The use of cell therapy can help your body naturally reduce a harmful chemical imbalance; restore cell to cell communication; and regenerate new tissue all adding up to a joint with lower pain and higher function without side effects or the inconvenience and risk of major surgery.

 

Hour Top Docs 2016 - Laith Farjo MD

We are pleased to announce that Dr. Laith Farjo has been selected as an Hour Magazine Top Doc for 2016, his fifth year in a row to receive this honor! Every year, Hour Magazine polls physicians in Southeast Michigan and asks them to rate physicians they feel are exceptional - the highest ranking of these doctors are rated a Top Doc by the magazine.

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