Mesenchymal Stem Cells Can Potentially Treat Non-Union Fractures

Sometimes bone fractures have trouble healing. Such fractures are called “stable non-union fractures,” and they represent major clinical challenges. There are few treatment options for stable non-union fractures, and such conditions represent a major health issue. Fracture treatment options include bone grafting and/or remodeling of the fracture through open reduction and internal fixation (ORIF). In general, ORIF involves the use of plates, screws or even an intramedullary rod to stabilize the bone. Other, less-invasive care options such as treatment with bone morphogenic proteins (BMPs) and other types of bone stimulators are also available.

Can mesenchymal stem cells help such fractures heal better? Centeno and his colleagues at Regenexx conducted their own original research study that shows that some patients probably can be helped by the same sorts of procedures that they use to treat knees. This procedure includes bone marrow aspiration from the crest of the top of the pelvis (the ilium). The mesenchymal stem cells are isolated from the bone marrow and cultured for a few days. Then the expanded and prepared mesenchymal stem cells are applied precisely to the area that needs healing by means of c-Arm fluoroscopy. Sounds good? Yes it does, but to show that it works requires a tried and true clinical study. Centeno’s group has done exactly that, but the number of patients in this study is small. Still this paper represents one of the first examinations of stem cells treatments for stubborn fractures they resist healing.

In this paper, six patients were evaluated. All six had chronic fractures that had not healed (chronic fracture non-unions). There were four women and two men in this experimental group, and they had suffered from these fractures for an average of 8.75 months. The range of the times the patients had lived with these fractures ranged from 4- 18 months, but one patient had lived with their fracture for over 100 months.

All six patient were treated with their own stem cells that were extracted by means of bone marrow aspirations, cultured in the laboratory for 3- 7 passages, and then suspended in phosphate-buffered saline and lysate from peripheral blood platelets. All mesenchymal stem cells were assessed by microscopic examination and flow cytometry to ensure that they expressed the proper surface proteins. Mesenchymal stem cells were then injected percutaneously by means of a sterile trocar, guided by fluoroscopic imaging into the site of the stubborn fracture. To determine if the fractures healed, patients were scanned with X-rays, and computerized tomographic (CT) imaging.

Only five of the patients could be contacted for follow up, but the results are somewhat encouraging. The first patient was a 37-year old smoker (1/4 pack a day) who had suffered with a non-healing fracture for 9 months, but only 2 months after the treatment, was back to “full activities.” An X-ray at 14 months after healing showed excellent healing of the fracture.

The second patient was an 82-year old woman who had suffered from several fractures because of osteoporosis. She had stem cells implanted into her fractured back, and by eight months after the treatment regime, she showed advanced healing of her back fracture. Within four to six weeks after the transplant, the patient walked normally for her age and enjoyed new activities, albeit with age restrictions.

The third patient was a 68-year old woman with a long-time history of multiple sclerosis. She had an 18-month fracture that had not healed in her foot and had to walk with a walking boot immobilizer. Follow-up X-rays showed that after 2 and 6 months she had moderate healing of her fracture and returned to normal activities by 4-6 weeks after the transplant. Unfortunately, she dropped an object on the same foot at 7 months after the procedure and no further follow-up seemed practical.

The fourth patient is a 59 year old woman who had a 40-year history of a traumatic hip fracture and hamstring tear. Unfortunately, her follow up x-rays failed to show any signs of healing.

The fifth patient is a 67-year old man with a 4-month lower leg fracture. He also had type II diabetes mellitus, and coronary artery disease. This patient returned to full walking 4-6 weeks after the procedure. 5 months after the transplant, his x-rays showed signs of healing. No further follow up was possible.

Four of the six patients treated with their own mesenchymal stem cells showed good healing of the fractures that resisted healing through conventional means. The only fracture that showed no signs of healing was a 40-year old fracture that was difficult to immobilize. It is possible that the lack of immobilization caused the bone, which reacts to stress forces, caused this fracture that had adapted to being broken, and could no longer produce signals necessary for repair.

While this study is preliminary, the results support the hypothesis that a patient’s own mesenchymal stem cells are a potential alternative treatment for the treatment of stubborn, fractures that refuse to heal.