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    Looking Toward the Future of Stem Cells in Orthopaedics

    Dr. Thomas Einhorn and Dr. George Muschler weigh in on stem cell therapy, one of the hottest topics in orthopaedics today.

    By Susan Doan-Johnson

    The role biologics will play in the future of orthpaedic surgery remains unclear.

    There certainly have been disappointments. For example, a decade of research and clinical use of growth factors – namely, bone morphogenic proteins (BMPs) – did not pan out the way researchers had hoped.

    “We were banking on BMPs changing orthopaedic surgery,” said Thomas Einhorn, MD, from Boston University, in a press conference at the recent American Academy of Orthopaedic Surgeons (AAOS) Annual Meeting. BMPs, however, “have not lived up to the promise,” he said.

    But there are reasons to remain optimistic as the focus moves to cellular-based therapies – primarily stem cell therapy. Dr. Einhorn believes stem cells will not only be used to treat orthopaedic injuries, but will also be the foundation for drug discovery and research. They could, in fact, usher in an era of drug-based treatments for orthopaedic issues, he said.

    3 Applications for Stem Cells

    Dr. Einhorn’s particular interest is in how stem cells derived from bone marrow of adults can contribute to fracture healing. He began using autologous bone marrow grafting on fracture nonunions based on the positive results of a study by Hernigou et al [1], who achieved union in 53 of 60 patients with non-infected nonunions. In the study, bone marrow was aspirated from the patients’ iliac crests, centrifuged, and then reinjected as a bone marrow aspirate concentrate that contained progenitor and other mononuclear cells.

    Stems cells can also be used to treat patients with osteonecrosis of the femoral head. At a forum on stem cells at the Annual Meeting, Dr. Einhorn shared his case series of patients with stage 1 or stage 2 osteonecrosis who were treated with stem cells. At 1 year of follow-up, 75% of these patients improved significantly without surgical intervention.

    Dr. Einhorn is most excited about the possibilities for preventing progression of osteoarthritis of the knee – in fact, he referred to it as a “home run.” Human and animal studies have yielded positive results, he said, including pain reduction when compared with controls. The key, he said, will be to inject the stem cells where they are needed so that they are not washed away by synovial fluid.

    Questions and Cautions

    George Muschler, MD, from the Cleveland Clinic, also speaking at the AAOS press conference, agreed that stem cell therapy is one of the hottest topics in orthopaedic surgery today.

    He cautioned that much research is still needed to define how stem cells should be used in orthopaedic applications. This will take a concerted effort from a network of clinical investigators who are working together to answer questions about safety, efficacy, and long-term durability of stem cell therapy in orthopaedics, Dr. Muschler said.

    One of the challenges will be the personal nature of stem cell therapy. Can stem cells be harvested and implanted from one person to another, or is autologous stem cell therapy the best option? Similarly, how will stem cells from one part of the body behave in different applications? For example, will avascular necrosis, osteoarthritis, and fracture nonunion respond the same way to the same type of stem cell?

    Both Dr. Muschler and Dr. Einhorn believe the answer to the latter question is no. “We need to be prepared to wrestle with the fact that when we take a cell from its natural milieu and transplant it into another site, it may not behave as we expect,” Dr. Einhorn said.

    The delivery vehicle could be an issue in this respect as well. Right now, most surgeons harvest the cells from the patient, centrifuge them, and then reinject them into the patient. This is a low-risk procedure, Dr. Muschler said.

    But “surgeons may take cells and mix them with whatever vehicle they believe will work and then implant them,” Dr. Einhorn said. The problem is there is little data on which delivery vehicles are appropriate for the patient – some delivery vehicles could end up being toxic, or the stem cells and delivery vehicle could work against each other, rendering the treatment ineffective. This highlights the need for further research on stem cells and how they should be delivered to the patient, Dr. Einhorn said.

    Encouraging Study Results

    Research is ongoing, of course, and Dr. Einhorn and Dr. Muschler are encouraged by the recently published study by Vangsness et al. [2] The study showed that a single stem cell injection of adult human mesenchymal stem cells (MSC) following meniscus knee surgery could provide pain relief and aid in meniscus regrowth after partial medial meniscectomy.

    The study involved 55 patients, ages 18 to 60, who underwent a partial medial meniscectomy at seven medical institutions. Patients were randomly placed in one of three treatment groups:

    • Group A patients (18) received a “low-dose” injection of 50 million stem cells 7 to 10 days after meniscus surgery
    • Group B patients (18), received a higher dose of 150 million stem cells
    • Control Group patients (19) received sodium hyaluronate only

    Patients were followed for 2 years to assess safety, meniscus regeneration through MRI and X-ray images, overall condition of the knee joint, and clinical outcomes. While most patients had some arthritis, patients with severe arthritis (level three or four) in the same compartment as the meniscectomy were excluded from the study.

    Key findings of the study included the following:

    • No ectopic tissue formation or “clinically important” safety issues were identified.
    • As determined by MRI, there was “significantly increased meniscal volume” (defined as at least a 15% increase in meniscal volume) in 24% of patients in the low-dose injection group (A) and 6% of the high-dose injection group (B) at 1 year. There was no statistical increase in meniscal volume at 2 years.
    • No patients in the control group met the 15% threshold for increased meniscal volume.
    • Patients with osteoarthritis experienced a reduction in pain in the stem cell treatment groups; there was no reduction in pain in the control.

    References

    1. Hernigou P, Poignard A, Beaujean F, et al. Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am. 2005;87(7):1430–7
    2. 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 Jan 15;96(2):90-8.