Bone Marrow Stem Cell Therapy
Overview: Advanced Orthopedic Specialists was the first orthopedic private practice to offer state of the art cell based therapies to our patients in the area. Every treatment is not for every patient, and at Advanced Orthopedic Specialists we try very hard to ensure you receive a specially tailored and personalized treatment designed specifically for you.
What are they?
Our body stores cells required for repair within specific areas of our body. One such area is within your bone marrow. This is the space within the middle of your bone rich in cells used to regenerate damaged cells. Some of the stem cells found in this space are progenitor cells. These are matured stem cells used to repair damaged tissue such as bone and cartilage. Progenitor stem cells may be more efficient than normal stem cells found in your blood at repairing bone and cartilage but have lost some of their ability to form all different types of tissue.  Think of progenitor cells as stem cells that are more mature and like a young man in college majoring in biochemistry. They are bigger, smarter and more efficient than their younger stem cell cousins in elementary school. These younger cousin cells have the potential to mature into different cell lines, but we only need them to mature into bone and or cartilage cells. Thus, these progenitor stem cells are perfect for orthopedic conditions. Although other tissues in our body may have a higher number of stem cells, they are less likely to form the cells and tissue we need. Many of the same growth factors found in platelet rich plasma are found abundantly in your bone marrow. Specific stem cells called pericytes which support our vascular system are found within our bone marrow and they become important in the paracrine cell to cell communication. When our joints become diseased, this cell to cell communication breaks down and bone marrow derived stem cells as well as other factors help restore this normal communication. Finally, very important plasma proteins are found within your bone marrow including Intrluleukin-1 Receptor Antagonist Protein (IRAP) and Alpha 2 Macroglobulin (A2M). These plasma proteins are extremely important in reducing the destruction of your bone and joint. These very important proteins can be filtered and concentrated to help reduce damaging chemical reactions in your joint which cause destruction and pain.
Bone Marrow Stem Cell treatments can provide the following:
- Source of stem cells such as pericytes, and progenitor cells to help repair damaged tissues especially bone and cartilage cells and help cells communicate with each other.
- Platelet Rich Plasma (PRP) which provides important growth factors to help in the repair process.
- Plasma Proteins found in your bone marrow to reduce harmful chemicals in your joint.
 Levesque JP et al, Mobilization of Bone Marrow Derived Progenitors, Bone Marrow Derived Progenitors, Springer Berlin, 2007, p 4-28.
 Danisovic L et al, Comparison of in Vitro Chondrogenesis Potential of Human Mesenchymal Stem Cells Derived from Bone Marrow and Adipose Tissue, Gen Physiol Biophys, 2009 March, 28 (1) 56-62.
 Caporali A et al, Contribution of Pericyte Paracrine Regulation of the Endothelium Angiogenesis, Parmacol Ther. 2016, Oct 11, 30179-6.
 Weng S et al, Identification of a2-macroglobulin as a master inhibitor of cartilage- degrading factors that attenuates the progression of post traumatic osteoarthritis, Arthritis Rheumatol. 2014 Jul: 66(7) 1843-53
 Dinarello, CA et al, Treating inflammation by blocking interleukin-1 in humans; Semin Immunol. 2013 Dec 15 25(6) 469-84.
How does this work?
You will have the area over the front or back of your pelvis numbed with a local anesthetic like what you receive at the dentist. In addition, we provide you with medications to relax you. A specially designed needle is than used to enter the middle of your pelvic bone to remove the bone marrow concentrate. This concentrate is than processed in a sterile manner to further concentrate the progenitor, stem and pericyte cells as well as the platelet rich plasma into a fibrin material that is injected directly into the area of concern. These regenerative cells work on numerous biochemical pathways in your joint to help reduce pain and inflammation as well as increase cell-to-cell communication (paracrine signaling) resulting in improved function of the joint over a 3-4 month period. The pathways and mechanism of how this occurs is still debated, and very complex, but one possible theory could be:
Restorative Phase- The bad, destructive chemicals within the joint are reduced. Interleukins and cytokines causing chronic destruction to the joint are reduced to restore a normal balance.
Communicative Phase- Cells that have lost their ability to communicate with each other are now restored and this cell to cell communication causes a paracrine event. The cell function is restored so the joint can function in a more normal manner.
Regenerative Phase- Once the chronic destructive phase is reduced to a manageable level, and the cells begin to talk with each other and restore normal lines of communication, the joint can begin to function like a normal organ just like a kidney, brain or heart. Once these necessities for growth are established, the cells can start to regenerate. However, the actual number of cells regenerated may be minimal in comparison to the changes occurring with the restorative and communicative phase.
Although this is not a complete list, it is a general guideline to help you understand whom may be the ideal candidate for this procedure. You and your surgeon will always find exceptions since not every patient responds the same to each treatment:
- Patients looking for longer term pain relief of 4 or more years.
- Diagnosed osteoarthritis of the joint.
- Stable joint with giving away, locking or instability not occurring more than 2 times per week.
- Lack of severe bowing of the joint (less than 8-10 degrees of bowing)
- Lack of frequent severe joint swelling requiring needle aspirations (removing water from the knee)
- Lack of severe stiffness of the joint with range of motion within 20 degrees of normal motion.
- Willing to participate in additional therapies to improve the health of the joint
Safety of this procedure:
This procedure has been used for many years with a very good safety record. Laula MM and colleagues reviewed all the clinical trials using intravascular stem cell therapy in humans through the national database, and found that in over 1012 participants, they did not detect any association between acute toxicity, organ system complications, infection, death or malignancy and the only adverse event was transient fever. Another researcher reviewed over 1873 patients from 1990 to 2006 who received autologous bone marrow stem cell therapy at the University of Paris and concluded that there was no risk of cancer or cancer formation. In fact, he found that the normal rate of cancer in this patient population reduced from an expected number of 97 to 108 cases down to 58 cases. Thus, the actual rate of cancer in these treated patients was lower than expected.
A long term, retrospective study conducted by Mendoca injecting Bone Marrow Concentrate (BMC) into 14 patients with spinal cord injury. All subjects displayed variable improvements in tactile sensitivity, and eight subjects developed lower limbs motor functional gains, principally in the hip flexors. Seven subjects presented sacral sparing and improved American spinal injury association impairment scale (AIS) grades to B or C - incomplete injury. Nine subjects had improvements in urologic function. Statistically significant correlations between the improvements in neurological function and both injury size and level were found. Most importantly, no adverse events occurred in this sensitive procedure. In another meta-analysis (a review of numerous studies) of 78 studies using bone marrow derived stem cell therapy for cirrhosis of the liver concluded that there were no adverse events or complications.Thus, we can see from this short review that there have been little to no adverse events with this treatment and it is a very safe procedure.
 Lalu MM et al, Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A systemic Review and Metanalysis of Clinical Trials. PLoS One. 2012 Oct 25 7(10) e47559.
 Herniguo P et al, Cancer risk is not increased in patients treated for orthopedic disesases with autologous bone marrow concentrate. J Bone Joint Surg Am, 2013 Dec 18: 95(24) 2215-21.
 Mendoca et al Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury. Stem Cell Research and Therapy, 2014 Nov 17;5(6):126.
 Pan XW. Bone Marrow-derived mesenchymal stem cell therapy for decompensated liver cirrhosis: a metal-analysis. World Journal of Gastroenterology, 2014 Oct 14;20(38):14051-7.
Efficacy of Treatment:
Overall, most of the studies evaluating the use of this treatment have been encouraging but not conclusive. One such study is the use of bone marrow concentrate (BMC) injection compared to an orthopedic surgery used to grow cartilage cells in a culture and re-implant these into a surgically created pouch in the damaged joint called Autologous Chondrocyte Implantation (ACI). The ACI procedure requires two invasive surgical treatments and prolonged rehabilitation. On the other hand the bone marrow concentrate only required the simple injection to the knee without any significant pain or rehabilitation. Seventy-two (72) patients were in each group and both groups improved in all parameters. Interesting enough, only patients younger than the age of 45 improved with the ACI surgery. However, age did not alter results in patients receiving the bone marrow concentration.Another study evaluating the use of bone marrow concentrate in combination with a procedure that straightens the knee (called a high tibial osteotomy or HTO) revealed some encouraging results. Seventy-six (76) patients were split into two groups. The first group received the standard joint straightening procedure (HTO) along with a micro-fracture technique (holes placed in the bone to stimulate cartilage-like formation) to help repair the damaged cartilage. The second group had the same HTO procedure but they added culture expanded bone marrow cells to the knee. They were followed for 2 years and had a follow up MRI. The bone marrow group had statistically significant improvements in all the measurement scores including improvements of the cartilage as seen on the MRI scans. Another orthopedic surgeon in Colorado has used a technique of culture expanded bone marrow cells (meaning these were grown in a lab) and then re-injected into the knee. In a single case study report, the researcher could show an improvement in clinical outcome with improvements seen on follow up MRI of the knee. Further in-vitro studies (Latin for “in glass”) which is studying cells outside their environment revealed that bone marrow cells can differentiate into cartilage cells better than adipose derived cells.
 Nejadnik H. et al Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. American Journal of Sports Medicine 2010 Jun;38(6):1110-6
 Wong, KL. et al 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. Arthroscopy 2013 Dec;29(12):2020-8
 Centeno CJ Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physicians, 2008 May-Jun;11(3):343-53
 Dansovic L, Comparison of in vitro chondrogenic potential of human mesenchymal stem cells derived from bone marrow and adipose tissue. Gen Physiol Biophys 2009 Mar;28(1):56-62.
Convenience of this Procedure:
This procedure is done in the office setting within 30 minutes. You may require someone to drive you home if you choose to use an oral sedative for the procedure. You can resume all your normal activities within reason the day of the procedure. There is no need for time off work and there are limited follow up visits. We do ask most patients to perform simple home exercises to help heal the joint. Other patients are encouraged to use a brace for 3 months. The pain relief from this procedure may not occur until 3 months, and patients with severe arthritis may take 4 or more months.
Pain of this Procedure:
There is minimal pain associated with this procedure. Some people may have some soreness around their pelvis along with some bruising for up to a week. You are provided with pain medication and muscle relaxers if needed for the procedure. There is minimal if any swelling or pain to the joint injected.
No insurance plans currently cover this procedure. These expenses may be reimbursable through qualified Health Spending Accounts (HSA), Flexible Spending Account (FSA), Medical Savings Account (MSA), or Health Reimbursement Arrangement (HRA). Please contact your plan administrator for details. Deferred payment plans are available if you are interested. Our surgical scheduler can provide you with the details of this simple plan. The cost of this procedure covers the cost of the harvesting, processing and delivery of the cells. This does not include normal office visits including x-rays, co-pays, or additional therapies. When considering price comparisons, please realize the following:
- We have the most experience in recognizing the most appropriate patients for these treatments as well as the most advanced harvesting, processing and delivery of these cells with over 12 years of experience and over 4,000 patients treated. The process we use can increase the number of harvested cells by over 300% from normal harvesting techniques and we can capture over 90% of the important cells where many other systems capture a maximum of 50%.
- We have developed easy to follow pre-and post procedure protocols which help ensure a positive outcome.
How long will these treatments last?
Patients rightfully ask this question. Here is some evidence to show that this is not a short-term solution, but hopefully a long-term solution. First, many of the studies above show results at 2 years and some as short as 6 months. However, this does not mean that the treatment stopped working at this interval. This merely means that the study was designed to stop at this point. If you look at some of these studies, there are some promising results showing positive structural reversal of the arthritic disease. For example, Koh et al in his arthroscopic second look study revealed reversal of the arthritic changes on visual inspection of the knee through arthroscopy. This finding was confirmed by the South Korean dosing study. In addition, Khanh Hong-Thien Bui and colleagues found positive structural changes on serial MRI’s.  Thus, we can conclude that this is not just a band aide type of treatment, but this evidence helps point us in the direction of positive reversal of the underlying destructive process of arthritis. This is unlike many other current treatments available in orthopedics.
Some more recent studies from Iran show further long term success. Eighteen patients were treated with a bone marrow concentrate in multiple joints including knee, ankle and hip and followed for 30 months with careful laboratory, radiographic and MRI studies. The research team reported the “All” patients received therapeutic benefits confirmed by pain and function scores and were confirmed by MRI. Researchers at the University of Paris followed 534 patients up to 18 years after a bone marrow stem cell treatment for avascular necrosis of the hip which is an arthritis caused by the lack of blood supply to the hip. This long-term study revealed that only 15.7% of the patients went on to receive a total hip after this treatment and many of the x-rays and MRI’s of the hip stabilized.
We also have a “white paper” result from a very interesting long term study comparing bone marrow stem cell therapy to our traditional total knee replacement in elderly male patients. A white paper is a study which is not yet published and thus it has not been peer reviewed and one must be careful in using this data because it has not yet been validated. However, this same researcher has published hundreds of peer reviewed studies and is a very respectable source. This study took 60 elderly male patients all 85 years old or older. Group A was treated with the standard total knee replacement for both knees. 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 6 yrs. (ranging from 2 to 15 yrs.), the patients in Group B (stem cell group) had the following:
- Improved knee function scores (Knee Society Scores)-3-point improvement for the stem cell group vs. 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- None 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.
A large multi-national, multi-center study evaluating patients of all ages with all levels of severity gives us some further evidence that this is a longer term treatment for arthritis. In the study by Michalek J, et al. entitled “Autologous adipose tissue-derived stromal vascular fraction cells in patients with osteoarthritis,”(Cell Transplant, 2015 Jan 20. doi: 10.3727) followed 1128 patients for up to 54 months (over 4 yrs). A majority of these patients (63%) had at least 75% improvement of pain and function and 91% had at least 50% improvement. However, obese patents and patients with more severe arthritis took longer to respond. This is one of the largest and longest term study showing promising positive results in the longer term. Our own experience confirms this result. Our own unpublished evaluation of pain and function using a visual analog scale and the WOMAC on hundreds of patients receiving a similar procedure for over 3 years reveals similar results with an excellent safety profile and no serious adverse events.
Most of these studies are not controlled, blinded, or randomized, but they do show a common pattern of:
- This is a safe procedure with very low rates of complications
- Consistent reduction of pain.
- Consistent restoration of function.
- High rate of patient satisfaction.
- Improved MRI or physical findings (microscopic or arthroscopic).
 Koh YG et al, Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy, 2013 Apr; 29(4) 748-55.
 Khanh Hong-Thien Bui et al , Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study, Biomedical Research and Therapy, 2014 (1):02-08
 Emadedin M., et al, Long-Term Follow up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle or Hip Osteoarthritis, Arch Iran Med. 2015, Jun;18(6): 336-44
 Hernigou, P, et al, Cell Therapy of hip necrosis with autologous marrow grafting , Indian J Orthop.2009 Jan-Mar; 43(1): 40-45
 Michalek J et al., Autologous adipose tissue-derived stromal vascular fraction cells in patients with osteoarthritis, Cell Transplant, 2015 Jan 20. doi: 10.3727