During the AAOS Now 2014 Forum, “Stem Cells in Orthopaedics: Myth, Miracle, or Something In-between,” Thomas A. Einhorn, MD, chairman of the department of orthopaedic surgery and professor of orthopaedic surgery, biochemistry and biomedical engineering at Boston University, focused on the use of bone marrow aspirate concentrate (BMAC) for treating nonunions, fractures, and osteonecrosis.

AAOS Now

Published 6/1/2014
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Frank B. Kelly, MD; Mary Ann Porucznik

Applying Stem Cells to Orthopaedic Conditions

Using bone marrow stromal cells to treat nonunions and osteonecrosis

The ability of stem cells to divide and become more specialized cells—such as bone, blood, or muscle—makes them attractive agents in many areas of medicine. Additionally, the ability to harvest stem cells from an individual and reimplant them in the same individual, thus potentially reducing or eliminating the risk of infection, makes stem cell therapy appealing to both patients and physicians.

Although not yet widespread in orthopaedics, the use of adult stem cells to address musculoskeletal conditions is an intriguing concept. In particular, the use of bone marrow stromal cells has attracted the attention of researchers.

Stem cells may be distinguished from other cells by the following characteristics:

  • they have the ability to self-renew
  • they can continue to divide for a length of time
  • under certain conditions, they can be induced to differentiate into specialized cells with distinct functional characteristics (phenotypes) including, but not limited to, cardiac, liver, fat, bone, cartilage, nerve, and connective tissue cells

Nonunions
“In 2005, Philippe Hernigou, MD, and his colleagues at the Hôpital Henri Mondor, in Creteil, France, reported his experience using BMAC for treating nonunions,” began Dr. Einhorn. “This study involved 60 patients with a tibial shaft nonunion. Dr. Hernigou aspirated about 180 mL of autologous bone marrow from both iliac crests, filtered and concentrated the cells, and injected them into the nonunion.”

Of the 60 fractures, 53 went on to heal completely within 6 months. “But what was interesting,” said Dr. Einhorn, “was that when the researchers reviewed the radiographs, they found a positive correlation between the volume of mineralized callus on radiograph at 4 months and the number and concentration of fibroblast colony-forming units (CFU). The seven fractures that didn’t unite had the lowest concentration of CFUs.”

When he began using BMAC to treat nonunions, Dr. Einhorn applied the lessons he learned from Dr. Hernigou and his trauma colleagues. “The first thing I did was make sure I didn’t have to flip the patient in the middle of the surgery. My technique involves identifying the anterior superior iliac spine with the patient in the supine position and a bump under the left hip. Using image intensification, I insert the needle right down the alley of the inner two tables of the ilium. This enables me to go deep and get 150 mL of bone marrow with just two passes of the needle.”

The aspiration is done carefully; Dr. Einhorn tries not to draw more than 5 mL from one spot, so the marrow is not diluted. Using a VacLokTM syringe, he draws the first 5 mL, then turns the needle so that the next 5 mL is drawn from a different place. The process is repeated until the syringe is full. He then removes the needle, adjusts the orientation, and repeats the process (Fig 1). “Patients tolerate this treatment much better than they do an iliac crest bone graft,” noted Dr. Einhorn.

“This also give you the ability to concentrate the cells,” continued Dr. Einhorn. “With an autologous bone graft, you have no control over the concentration of cells. But with bone marrow aspirate, you can get up to 4 or 5 times the full concentration of cells.”

In addition, some evidence exists that ablation of bone marrow creates a short-term osteogenic response. “The idea that you’re aspirating a significant amount of bone marrow may actually result in a systemic response that ‘turns on’ the skeleton and makes it a more friendly place for cells to develop,” said Dr. Einhorn.

He cited a recent case of his involving a 49-year-old man with a 9-month-old tibial fracture nonunion on the medial side. Within 4 months of receiving the stem cell injection, the patient’s fracture was completely healed. “It’s an anecdote,” admitted Dr. Einhorn, “but given the circumstances, I think it was the stem cell treatment that made the difference.”

During the AAOS Now 2014 Forum, “Stem Cells in Orthopaedics: Myth, Miracle, or Something In-between,” Thomas A. Einhorn, MD, chairman of the department of orthopaedic surgery and professor of orthopaedic surgery, biochemistry and biomedical engineering at Boston University, focused on the use of bone marrow aspirate concentrate (BMAC) for treating nonunions, fractures, and osteonecrosis.
Fig. 1 When aspirating bone marrow, Dr. Einhorn inserts the needle down the alley of the inner two tables of the ilium and continues to turn the needle as it is withdrawn so that he does not draw more than 5 mL from any one spot.
Courtesy of Thomas A. Einhorn, MD

Osteonecrosis
Because approximately half of all hips with asymptomatic osteonecrosis of the femoral head will eventually collapse and require a total hip arthroplasty (THA), early attempts to preserve the femoral head are important. “And that’s what we’re doing with stem cells,” said Dr. Einhorn.

According to one study cited by Dr. Einhorn, patients with early asymptomatic osteonecrosis of the femoral head were randomized to receive either core decompression (CD) or CD plus autologous bone marrow. Results showed a significant reduction in pain and symptoms among those who received both CD and BMAC. Additionally, after 2 years, more than half of the patients who received CD only had undergone THA due to disease progression, but only 10 percent of those who received both CD and BMAC had gone on to have THA.

When he used a similar treatment, Dr. Einhorn found that patients with sickle cell disease had the best results and those with an etiology of steroid use, alcohol abuse, or transplantation had the worst prognoses. “In addition,” he noted, “when these conditions lead to severe trabecular bone loss and softening, extensive penetration of the femoral head with contrast material may suggest future collapse. Use of bisphosphonates may be indicated.”

Dr. Einhorn noted that osteonecrosis of the femoral condyle may also be treated with BMAC. Using image intensification is important to ensure that the needle is properly placed, he said, because the medial femoral condyle is more distal than the lateral femoral condyle on lateral radiographs.

Is osteoarthritis next?
“I was asked to talk about the use of stem cells in treating nonunions and osteonecrosis, but what’s really needed is a treatment for the weekend warrior,” said Dr. Einhorn. “I think that the home run is applying stem cells to early osteoarthritis (OA).”

He referenced a recent study using cartilage defects in an equine model. Compared to treatment with microfracture alone, treatment with microfracture and BMAC resulted in increased fill of the defects and improved integration of repair tissue with surrounding cartilage. “There was more type-II collagen content, improved orientation of the collagen, and significantly more glycosaminoglycans in the BMAC-treated defects than in those treated with microfracture alone,” he said.

“But the paper that really impresses me,” he continued, “came out just recently and involved 55 patients who underwent partial medial meniscectomy and were treated with a preparation of ex vivo cultured adult human mesenchymal stem cells (MSC). Patients were randomized to one of three treatment groups—low-dose MSC, high-dose MSC, and control (hyaluronic acid)—and received a single superolateral knee injection within 7 days of surgery.”

A significant increase in meniscal volume (defined as a 15 percent threshold) was found in 24 percent of the patients in the low-dose MSC Group and in 6 percent of the patients in the high-dose MSC group; no patients in the control group met this threshold. Additionally, based on a visual analog scale, patients with OA changes who received MSC experienced a significant reduction in pain compared with controls.

Frank B. Kelly, MD, is a member of the AAOS Now editorial board and served as cochair of the AAOS Now Forum; Mary Ann Porucznik is managing editor of AAOS Now.

Disclosure information: Dr. Einhorn— Medtronic, Anika, Harvest, Merck Bioventus, National Institutes of Health, Biomineral Holdings, HealthpointCapital, Implant Protection, NeoStem, Journal of Bone and Joint Surgery, Elsevier, Lippincott

References

  1. Hernigou P, Poignard A, Beaujean F, Rouard H: Percutaneous autologous bone-marrow grafting for nonunions: Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 2005;87(7):1430-1437.
  2. Mont MA, Zywiel MG, Marker DR, McGrath MS, Delanois RE: The natural history of untreated asymptomatic osteonecrosis of the femoral head: A systematic literature review. J Bone Joint Surg Am 2010;92(12):2165-2170. doi: 10.2106/JBJS.I.00575.
  3. Gangji V, Hauzeur JP: Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: Surgical technique. J Bone Joint Surg Am 2005;87 Suppl 1(Pt 1):106-112.
  4. Fortier LA, Potter HG, Rickey EJ, et al: Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am 2010;92(10):1927-1937. doi: 10.2106/JBJS.I.01284.
  5. Vangsness CT Jr, Farr J 2nd, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M: Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: A randomized, double-blind, controlled study. J Bone Joint Surg Am 2014;96(2):90-98. doi: 10.2106/JBJS.M.00058