Bone marrow stem cell therapy and Prolotherapy: Published review 7 case histories

Ross Hauser, MD

Stem cell therapy can be confusing to many patients because there are many services being offered as stem cell therapy. The most common are:

  • Bone Marrow derived stem cell therapy
  • Adipose (Fat cells) derived stem cell therapy

Both of these treatments are stem cells from you.

There are also stem cell therapies that are not really stem cell therapies. These are:

  • Amniotic stem cell therapy, which some are now more appropriately calling: Amniotic Membrane Injections
  • Placenta stem cell therapy, which some are now more appropriately calling: Placenta Tissue Injections

Many emails that come into our office ask us to compare various form of stem cell therapies. Most of the emails we get are from people who have recently attended a seminar in which they were introduced to the idea that a new born baby was willing to donate his/her amniotic fluid or cord blood or placenta afterbirth material to them to replace the patients own old or weakened stem cells. The use of this donated material is not stem cell therapy as there are no stem cells in the treatment. This is discussed further in my article on “amniotic stem cell therapy.

Bone marrow aspirate concentrate, stem cell therapy, or bone marrow Prolotherapy refers to the use of bone marrow concentrate injections into areas of degenerative joint disease to stop and repair degenerative changes. The use of bone marrow aspirate relies on the action of stem cells to initiate and guide this joint repair.

In this article we will summarize research including presenting to you our own published research on the benefits of Bone Marrow Aspirate Concentrate or “Stem Cell Prolotherapy.” Stem cells from you.

Mayo Clinic and Yale University studies on your own bone marrow stem cells

Doctors at the Mayo Clinic and Yale University published their research on the benefits of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis in the American Journal of Sports Medicine. Here is the summary of that research:

  • Bone marrow aspirate concentrate (BMAC) is increasingly used as a regenerative therapy for musculoskeletal pathological conditions despite limited evidence-based support.
  • HYPOTHESIS: Bone marrow aspirate concentrate will prove feasible, safe, and efficacious for the treatment of pain due to mild to moderate degenerative joint disease of the knee.

In their single-blind, placebo-controlled trial, 25 patients with bilateral knee pain from bilateral knee osteoarthritis were randomized to receive Bone marrow aspirate concentrate into one knee and saline placebo into the other.

  • Early results show that Bone marrow aspirate concentrate is safe to use and is a reliable and viable (stem cell) cellular product. Study patients experienced a similar relief of pain in both Bone marrow aspirate concentrate- and saline-treated arthritic knees.(1)

Doctors in New Jersey at the Department of Orthopedic Surgery, Jersey City Medical Center published their findings in support of this research, in the World journal of orthopedics, here is what the paper said:

“The current literature demonstrates the potential benefits of utilizing concentrated bone marrow aspirate for the repair of cartilaginous lesions, bony defects, and tendon injuries in the clinical setting.

The studies have demonstrated using concentrated bone marrow aspirate as an adjunctive procedure can result in cartilage healing similar to that of native hyaline tissue, faster time to bony union, and a lower rate of tendon re-rupture.”(2)

Doctors announced their findings in the Archives of Iranian medicine on patients who received stem cell therapy in the hip, knee, or ankle for treatments of osteoarthritis. All seventeen patients in the study exhibited therapeutic benefits such as increased walking distance, increased function, and reduced pain.”(3This 2015 study is considered a cornerstone study by some and it frequently referenced as it is here including citations in 5 studies in 2016 and 4 studies in 2017.

At the National University of Singapore, doctors publishing in the Journal of clinical orthopaedics and trauma cited this research among others in saying

  • “The versatility of mesenchymal stem cells (MSCs) as a treatment modality has landed it another repair target: osteoarthritis, a crippling cartilage disease that frequently afflicts the aged population. Through many studies, this newly discovered method has been shown to significantly alleviate the pain experienced by osteoarthritic patients. “(4)

Doctors at Georgia Regents University wrote in the Clinical and translational medicine in support of the above research:

  • “Current pharmacological treatment strategies are ineffective to prevent the osteoarthritis progression; however, cellular therapies have the potential to regenerate the lost cartilage, combat cartilage degeneration, provide pain relief, and improve patient mobility. One of the most promising sources of cellular regenerative medicine is from mesenchymal stem cells.”(5)

What is Bone marrow concentrate injections?

Direct Bone Marrow Injection

Using stem cells taken from a patient’s bone marrow is becoming a therapy of interest due to the potential of these mesenchymal stem cells to differentiate into other types of cells such as bone and cartilage.

Bone Marrow is the liquid spongy-type tissue found in the hallow (interior) of bones. It is primarily a fatty tissue that houses stem cells which are responsible for the formation of other cells. These mesenchymal stem cells (MSC), also called marrow stromal cells, can differentiate (change) into a variety of cell types including osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells), adipocytes (fat), fibroblasts (ligament and tendon) and others when reintroduced into the body by injection. Bone marrow also contains hematopoietic stem cells that give rise to the white and red blood cells and platelets.

In clinical observations at Caring Medical and Rehabilitation Services CMRS great benefit is seen in injecting bone marrow directly after extracting it.

The theory is that the number of stem cells is not as important as how long they live in their natural environment. In other words, when the bone marrow is directly injected, the source of stem cells is fresh and has great potential for healing. We also believe that the body knows best – it can use these immature cells to regenerate all injured tissues in the joint.

One study conducted in Japan shows the ability of mesenchymal stem cells to travel to the injury site and regenerate cartilage when directly injected into the knee joint.(6) This study was done in rats with injured multiple knee injuries – anterior cruciate ligaments (ACL)meniscus tears and damaged femoral condyle cartilage (cartilage that cushions the knee).

In these rats, bone marrow was extracted from the tibia and injected into the knee joint. In all eight rats, the stem cells moved into the injured ACL tissue and in six of the eight rats the stem cells moved into the injured meniscus.

The stem cells showed proliferation for up to 35 days. In other words the stem cells were changing and repairing/growing cartilage and tissue in these injured areas. The results showed repaired tissue in the injured knee joints. The researchers concluded that when a large number of mesenchymal stem cells are injected into a multiple injury knee joint they can move to the specific areas of injury and regenerate cartilage.

Seven patient outcomes in the medical literature

In the medical journal Clinical Medicine Insights Arthritis and Musculoskeletal Disorders, Caring Medical published our findings in seven patients.

Patient case 1 – Ankle Pain
A 59-year-old female patient come into our office with right ankle pain following a lateral sprain. The patient reported she could barely walk without severe ankle pain.

The patient had unsuccessful treatment with cortisone injections and was being recommended to ankle fusion based on X-ray and MRI finding that suggested osteoarthritis, avascular necrosis of the talus, and synovitis.

The patient received four bone marrow/dextrose treatments over a period of eight months.

  • At second treatment, the patient reported the ability to stand for long periods and walk for half a mile without pain.
  • At third treatment, she reported improved range of motion, less frequent pain, and ability to take two mile walks on hilly, uneven ground, although steep climbs still induced pain.

Patient case  2 – Knee pain
A 69-year-old male came into our office with pain in both knees, with his right knee significantly more painful.Pain resulted in frequent sleep interruption and limitation of exercise.

The patient had received prolotherapy at another office in the previous two years but felt that the treatment has reached its maximum ability to heal.

The patient was diagnosed with osteoarthritis and received five bone marrow/dextrose treatments in each knee at two month intervals.

  • Two months after the final treatment, the patient reported that he was completely free of pain or stiffness in both knees, had regained full range of motion, no longer suffered sleep interruption, and was no longer limited in exercise or daily life activities.

Patient case  3 – Hip Pain
A 76-year-old female came into our office with pain in both hips that had plagued her the last 3-4 years. Her left hip pain being more significant than the right. She was unable to walk more than a mile without significant pain. The patient had received a recommendation for hip replacement. X-rays revealed moderate to severe degenerative changes in both hips.

Degenerative disease of the lower lumbar spine were also noted.

The patient received seven bone marrow/dextrose treatments to each hip over a period of 12 months and adhered to a program of daily bicycle exercise.

  • She reported incremental improvements in pain and function at each visit. At the final visit the patient reported significant gains since the onset of treatment with respect to range of motion, resumption of exercise, reduced crepitus, and reduction of pain medication use by two thirds. She reported her overall improvement as 90%.

Patient case  4 – Knee and hip pain
A 56-year-old female came into our office with pain in both knees and her right hip. She reported the knee pain started 3 years prior. Pain was severe in the right knee, with frequent crepitus and instability, and had forced the patient to discontinue running. MRI with a previous physician had shown cartilage degeneration. Right hip pain had been intermittent for 16 years, but instability and continuous pain began six months before her first office visit.

The hip pain prevented sleep on the affected side, bicycle exercise had stopped for more than a year, and walking exercise was limited to three miles.

MRI with a previous physician showed a hip labral tear.

The patient received bone marrow/dextrose treatments for six visits with 8–10 week intervals.

  • The patient reported modest (20%–35%) overall improvement following these treatments. At the final two visits, both knees and right hip were treated with bone marrow prolotherapy injection. During the treatment period, the left hip was also treated for pain resulting from a flexor injury incurred following visit 1.
  • Two months after visit 6, the patient reported 65%–95% overall improvement for the three joints. She is able to walk for two hours, no longer has disturbed sleep, and has been able to resume bicycle exercise with minimal discomfort.

Patient case  5 – Knee pain
A 56-year-old male came into our office with pain in both knees. The patient is a former competitive weightlifter who continues to do strength training exercise. He complained of instability in both knees during exercise, as well as sleep interruption.

The patient received 29 bilateral dextrose prolotherapy treatments over five years.

At the final prolotherapy visit, sleep interruption was still present, pain intensity was 4/10, and pain frequency was 100%.

Four months later, the patient was treated with platelet-rich plasma. Three months after plasma treatment, the patient began a series of three bone marrow stem cell injection treatments (without dextrose prolotherapy) at 2–3 month intervals.

At the time of the second bone marrow stem cell injection treatments, stability was improved. At the time of the third treatment, pain intensity was 2/10 and pain frequency was 30%. Sleep was no longer affected. These gains were maintained for nine months.

Patient case  6 – Knee pain
A 69-year-old female came into our office with pain in both knees. She had been previously diagnosed with osteoarthritis, had arthroscopic surgery to both knees eight years earlier, and medial meniscus repair in both knees 15 years earlier.

The patient reported pain occurred climbing or descending stairs and with standing or walking for two hours. Pain interrupted sleep and limited participation in racquet sports and golf.

The patient received six treatments in both knees with dextrose prolotherapy over a ten month period.

  • After the first month of this period, the patient reported uninterrupted sleep, pain intensity of 2/10, resumption of limited golf, and an overall improvement of 50%–55%.

One year after the final prolotherapy, pain intensity had returned to 4/10 with a frequency of 20%, and sleep interruption had resumed. At this time, the patient received the first of two bone marrow stem cell injection/dextrose treatments, five months apart.

  • At the time of the second treatment, pain intensity was 1/10 with a frequency of 20%, sleep interruption was reduced by half, and patient-reported overall improvement was 90%.
  • Eight months following the final bone marrow stem cell injection/dextrose treatment, the patient reported being free of pain and able to resume full participation in all of her usual athletic activities.

Patient case  7 – Hip pain
A 63-year-old male came into our office with pain in both hips.

The patient received five treatments with dextrose prolotherapy in both hips over a period of 5 months. During this period, the patient reported overall improvement of 50%; however, this reduced to 30%–40% at the conclusion of the treatment period, at which time pain intensity was 6/10 increased but with less frequency.

Crepitus, previously absent, was now marked. At this point, the patient began a series of two bone marrow stem cell injection/dextrose treatments two months apart.

At the time of the second treatment, pain intensity reduced. Crepitus was reduced. Specific pain manifestations previously noted, including ischial tuberosity pain and lateral hip pain, had abated, and the patient reported being able to walk without a cane for the first time in years.

Two months after the second bone marrow stem cell injection/dextrose treatments, pain intensity was 1/10 with a frequency of 10%. The patient reported walking without a limp and no longer needing a cane.

Do you have a question about bone marrow aspirate concentrate Prolotherapy? Get help and information from our Caring Medical staff

1 Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O’Connor MI. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Am J Sports Med. 2017 Jan;45(1):82-90. doi: 10.1177/0363546516662455. Epub 2016 Sep 30. [Google Scholar]

2 Gianakos AL, Sun L, Patel JN, Adams DM, Liporace FA. Clinical application of concentrated bone marrow aspirate in orthopaedics: A systematic review. World journal of orthopedics. 2017 Jun 18;8(6):491.  [Google Scholar]

Emadedin M, Ghorbani Liastani M, Fazeli R, Mohseni F, 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. doi: 015186/AIM.003.  [Google Scholar]

4 Afizah H, Hui JH. Mesenchymal stem cell therapy for osteoarthritis. Journal of clinical orthopaedics and trauma. 2016 Sep 30;7(3):177-82.  [Google Scholar]

5 Burke J, Hunter M, Kolhe R, Isales C, Hamrick M, Fulzele S. Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis. Clinical and translational medicine. 2016 Aug 10;5(1):27.  [Google Scholar]

6 Agung M, Ochi M, Yanada S, Adachi N, Izuta Y, Yamasaki T, Toda K. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surgery, Sports Traumatology, Arthroscopy. 2006 Dec 1;14(12):1307-14.  [Google Scholar]

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