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Knee Stem Cell Therapy

Everything you need to know about treating a variety of knee joint conditions.

Overview of using stem cell therapy for knee conditions

Safe, effective and natural, stem cell treatments for knee joint conditions have a proven track record of cultivating increased functionality in the knee while also lowering pain and improving a patient’s quality of life. Read on to discover if you are a candidate for this procedure, and learn how cellular therapy can restore movement to one of the body’s most contingent areas.

1

What do we know about using stem cells for knees?

An overview of this specific therapy, explained in a way that is comprehensive and concise.

Adult autologous bone marrow derived stem cell therapy (meaning, stem cells taken from your own bone marrow) and/or Platelet Rich Plasma (PRP) can be used to treat a variety of conditions related to the knee joint. These conditions include:

  •  Arthritis
  • Tendonitis
  • Fractures or breaks in the bone
  • Cartilage injury
  • Infections

Every patient and knee is unique, and not everyone responds to treatment in the exact same way. For this reason, a proper evaluation and consultation consisting of a thorough physical exam and evaluation is first conducted, in addition to studies such as X-rays and MRI’s. Only then can an honest opinion can be given in regards to finding the best option for a patient’s condition.

Because adult autologous bone marrow derived stem cell therapy does not only provide stem cells but important plasma proteins and growth factors as well, this therapy can be used for a variety of conditions. However, we focus our discussion on studies of specific conditions evaluated in peer reviewed published studies.

‘Peer reviewed’ is a term referring to research which fellow physicians and expert researchers have critically reviewed and commented on in order to ensure that sound scientific methods were used to conduct the study in question. This method also ensures that any personal or industry bias has been reduced as much as possible.

2

Is there evidence that this works?

Evidence that this therapy is reliable and a worthy investment.

Adult Autologous Bone Marrow Derived Stem Cell Therapy has been used for numerous orthopedic conditions in and around the knee with excellent safety and efficacy, as evidenced through peer reviewed published studies.

We will review a few of these studies below and provide you with the references to these studies so that you may read and evaluate them yourself. These studies are intended to provide you with a body of scientific knowledge; but even so, you must consider that we are providing you with a one-sided review of results.

In addition, supporting and conflicting studies surrounding stem cell use appear daily. It is suggested that readers and potential clients perform their own review of the scientific literature available prior to committing to treatment.

3

Is bone marrow safe?

Testing has shown this treatment has proven and lasting results.

Cellular Health believes that before beginning to discussing a procedure, there should first be evidence that the procedure possesses far greater patient benefits than potential risks. This follows the principle of “Do no harm.” Fortunately, bone marrow concentrate and stem cells which come from the same patient being treated, without any manipulation, have a very good record of being safe.

A large study called the Safe Cell study evaluated numerous stem cell studies with over 1,012 patients being treated for a variety of serious medical conditions. This study concluded the following: “Based on the current clinical trials, MSC appears safe.”1

Further evidence of safety is seen in the work of Phillipe Hernigou from the University of Paris, who has been using bone marrow derived stem cell treatments for orthopedic conditions for over 30 years. Phillipe followed over 1,873 patients for an average of 12.5 years, with a combined total of over 7,306 MRI’s and 54,430 X-rays. Through all of this, no tumor formations were found. In fact, a lower rate of overall cancers was noted2!

4

How can we use bone marrow stem cells for knee arthritis?

Specific ways stem cells can benefit patients with arthritis.

Arthritis pains? Read our eBook on options for your arthritis now!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.

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 outcome3. 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.

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 (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 findings4.

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 marrow5.

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 horses6. 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.

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 findings7. A follow up study conducted in Italy found similar positive results8.

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 group9.

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 pain10.

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 replacement11. These findings were also discussed in a review article by researchers at Bristol University, UK12.

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 risks13.

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 surgeries14.

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.

If you would like to find out : AM I A CANDIDATE  or you would like to schedule a FREE CONSULTATION click away or dial 810-299-8552 to talk with someone. 

5

Who is a candidate for stem cell therapy for the knee?

Discover if you’re a candidate for therapy by reading about the conditions it can treat.

At Cellular Healing, our goal is to ensure that every patient who truly needs stem cell therapy receives treatment in a way that is most beneficial for them. If you would like to see all of our current options, please view our Arthritis Decision Sheet below.

New call-to-actionIf our team really believes you will not benefit from cell based therapy, we will be honest and tell you right away. Although the following is not a complete list, it is a general guideline to help you understand whom may be the ideal candidate for this procedure. Our goal is to recommend the best form or treatment for you based on numerous factors. Here are some factors we evaluate to find the best treatment for your specific and special condition:

  • Stable joint without frequent giving away or locking of the knee. If your knee feels unstable, gives way or locks more than two times per week, you may require an additional procedure such as an arthroscopic procedure to fix a tear or remove loose cartilage. The stem cell therapy treatment can be performed at the same time.
  • Lack of severe bowing of the joint. This normally means less than 10 degrees of bowing in either direction. As a rule, if you can see the bow of your knee through standard pants, stem cell therapy may not be recommended.
  • Lack of frequent severe joint swelling requiring needle aspirations. If you have water removed from your knee more than four times per year, stem cell therapy may not be recommended for you.
  • Lack of severe stiffness of the joint. If your knee has lost more than 20 degrees of normal motion, you may not be a stem cell candidate.
  • Willingness to participate in additional therapies to improve the health of the joint. Stem cell therapy has a higher rate of success when patients participate in frequent, simple, home-based therapy exercises, help reduce their weight, and adapt healthy diets.
6

How do you get the cells?

A look into the process of harvesting stem cells.

Although there are wide variations, many medical professionals follow the basic procedure of taking bone marrow from the pelvic bone using a special bone marrow needle called a Jamshidi needle. The technique used to harvest the bone marrow is important because there can be a 300% difference in the number of stem cell colonies based on how the bone marrow is removed15.

Most of the time, the larger amounts of bone marrow are concentrated into a smaller amount by use of a centrifuge (a device which spins at a fast rate), which separates the cells into specific layers. The layers align based on the specific gravity of each cell. Most, but not all of the important stem cells, proteins and growth factors end up in the middle layer of this process called the “buffy coat.” This rich layer is then removed carefully.

The red cells, such as hemoglobin which carry the oxygen throughout your body, are the heaviest cells; they make up the bottom layer. The lighter yellow layer is what was once known as the platelet poor plasma layer. This thinner, lighter platelet poor layer was once thought to be worthless, and was discarded in the biohazard trash. However, recent research and theory feels this layer can be concentrated into what is known as General Fluid Concentrate (GFC) with rich supplies of important proteins such as Interleukin 1- beta receptor antagonist or Alpha-2- Macroglobulin used to help reduce destructive chemicals in damaged joints16.

At times, extra bone marrow is harvested in very small batches under high suction to provide a bone marrow aspirate to inject into the area of damage without processing. This process is allowed due to the number of stem cells removed in ratio to the number of red blood cells - it is favorable for providing added numbers of stem cells and proteins while avoiding higher number of red blood cells, which can cause inflammation.

7

How are the cells delivered?

Get a better understanding of the procedure and what to expect during treatment.

After the cells are harvested and/or processed properly, we can deliver them to the area of damage or degeneration. This is typically done on the same day. In some cases, the injection is done under ultrasound or X-ray guidance. However, at times the area is so large and easy to reach with a normal needle that there is no need for ultrasound or X-ray.

Within 5 - 10 minutes after receiving the injected cells, patients can get up and walk, usually without any assistance. Patients can return to work and resume normal activities the next day. Simple, non-stressful exercises such as a stationary bike and walking are resumed in a few days.

In some cases, the bone marrow stem cells are delivered into specific areas of the bone on either side of the knee or into the knee cap. This is usually recommended if there are areas of acute bone marrow inflammation found on an MRI of the knee. If this procedure is recommended, it is normally delivered under the comfort and control of a surgical suite setting. A special bone marrow needle is carefully introduced near the damaged or inflamed bone; then, the damaged bone marrow cells are removed by suction, and the good cells are slowly infused into the bone. It is a simple “out with the bad and in with the good” concept. Sometimes, this is combined with an arthroscopic (tiny fiber optic camera) procedure within your joint to remove tears of the meniscus or loose pieces of cartilage. In this case, you may be asked to use a walker or crutches for one week following.

If you would like to see a video of the entire process, you can watch our in-office procedure video below.

 

 

If you would like to see a video of an operative procedure where we treat a torn meniscus and deliver stem cells to a specific area of damaged bone, you can watch the following video.

 

 

8

How much pain is expected?

What to expect in terms of pain both during and after treatment.

This is a question many patients ask, and it is something the staff at Cellular Healing takes very seriously. We try to reduce the discomfort of this procedure as much as possible and offer many different modalities and options. Personally, I (Dr. Loniewski) have had this procedure done twice in an office setting, and can testify to the safety, comfort, and efficacy of this treatment.

Every patient has different pain thresholds and different concerns about a medical procedure. For this reason, we offer a variety of options to experience this procedure. Most patients choose to have treatment done in our office under the effect of oral sedatives, narcotics, and a local anesthetic. However, if you would prefer to be unconscious for this procedure, this can be done under the care of a board-certified anesthesiologist at a local surgical center for an additional cost.

9

How long before I notice any improvement?

A general idea of the amount of time between the procedure and expected results.

With both procedures, most patients do not notice substantial improvement for approximately three months following treatment. In our clinical experience, there is a progressive reduction of pain and slow restoration of function. Every patient is unique and special, and the length of recovery can vary; however, our clinical experience is that most patients start to notice improvement around the three month mark with progressive improvement at six months and even more is seen at twelve months or longer. Peer reviewed research studies have shown that adult autologous bone marrow derived stem cell therapy has resulted in sustained relief for periods lasting over twelve years or more17.

10

How much does stem cell therapy for knees cost?

Understand ahead of time how much this procedure costs.

Although there is substantial evidence that Bone Marrow Derived Stem Cell Therapy is safe and effective, there is not yet a Medicare procedure code for this treatment. This also means no standard insurance carrier covers this procedure.

Other surgeries used to treat the knee such as arthroscopic meniscal removal or loose body removal are covered benefits with a insurance billing code; however, cell based therapies are not. If you have a health sharing plan such as Medi-share™, stem cell therapy may be covered since the cost of this procedure is much lower than a joint replacement. Most health sharing plans are affiliated with a religious organization, and you must choose this rather than Affordable Care Act (ACA) sanctioned plan.

In addition, if you have a health spending account, the expenses associated with this procedure may be offset by these accounts.

The staff at Cellular Healing are constantly looking for methods to reduce the cost while improving the outcomes of this procedure. Overall, our costs have been reduced substantially over the past few years. We also realize that not all patients are the same and that some may be able to benefit from lower cost harvesting and processing devices. Furthermore, some patients are requesting comprehensive treatment packages including exercise, nutrition and adjunctive health promoting therapies. For these reasons, we offer a wide variety of options to fit every patient’s arthritic condition and desires for additional, adjunctive proven therapies. Our team would be happy to review these options with you one-on-one to find the best fit based on your condition and personal desires.

Cellular Healing offers very effective bone marrow stem cell therapies starting at $2,950. Our ultimate stem cell therapy package offers state of the art stem cell processing and two additional customized platelet rich plasma injections coupled with nutrition optimization and whole body vibration, as well as low level laser therapy. Patients have access to a wide variety of options to help them return to a life with reduced pain and increased activity.

If you would like to learn more about these plans, please browse our Patient Services pages in the menu, or contact us for an immediate consultation.

11

Footnotes

Read the cited studies and texts that helped inform our knowledge on the effectiveness of this treatment.

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

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