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Bone regeneration is possible using stem cells
Researchers have developed methods to harness the power of stem cells to fill bone defects and improve bony ingrowth into implants.
Since bone is generally considered the easiest musculoskeletal tissue to repair, it is perhaps not surprising that the greatest advances in the use of stem cells in orthopedics have been for bone regeneration.
In 2001 Ranieri Cancedda, MD, published a letter in the New England Journal of Medicine describing the use of autologous bone marrow stromal cells to repair large bone defects in three patients. “These three patients now have a follow-up of more than five years and they are doing well,” said Cancedda, dean of biotechnology at the University of Genoa.
Osteoprogenitor cells were isolated from the patients’ bone marrow, expanded ex vivo and placed on macroporous hydroxyapatite scaffolds that were sized and shaped to fit each patient’s defect. The scaffolds were then implanted at the lesion sites. External fixation was provided for mechanical stability.
In Summary
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The first patient was a 41-year-old woman who was missing a 4-cm segment of the mid-diaphysis of the right tibia following an unsuccessful bone-lengthening procedure. The second patient, a 16-year-old girl, sustained the loss of a 4-cm segment of the distal diaphysis of the right ulna due to trauma. Patient three was a 22-year-old man who lost a 7-cm segment of the right humerus due to a plurifragmental fracture.
External fixation was removed 6.5 months after surgery in patient one, six months afterwards in patient two and 13 months afterwards in patient three. Radiographs and computed tomographic scans revealed abundant callus formation and good integration at the interfaces with the host bones two months after surgery in all three patients.
Under the most optimal conditions, recovery following a traditional bone-grafting procedure would have taken 12 to 18 months, Cancedda said. He is now conducting animal studies using scaffolds that totally resorb and is planning a major human study with the AO.
In the United States, George Muschler, MD, is gathering data on the more than 50 patients with long-bone nonunions that he has treated using the Cellect system from DePuy Orthobiologics. Muschler, the director of the Bone Biology Laboratory at the Cleveland Clinic, developed the technology on which Cellect is based.
Cellect uses bone marrow aspirated from the patient’s iliac crest. The marrow is placed in a vacuum-sealed chamber for 15 to 20 minutes, and through “selective retention,” white and red blood cells pass through the scaffold while 90% of the stem cells adhere to it. The cell-enriched scaffold is then placed in the defect.
“This is just one surgeon’s anecdotal experience, but our success rate thus far is 90% in treating established long-bone nonunions, which is as good as I ever did with cancellous autograft.” Muschler said that for easier defects he can achieve 100% fusion rates using allograft cancellous bone alone or sometimes mixed with demineralized fibers.
"I've elected to use Cellect in people with nonunions or in people with compromised tissue beds or compromised systemic biology where I think the added value is likely to make an appreciable clinical difference."
Muschler said that while other surgeons are collecting anecdotal evidence, it will be difficult to do a randomized study because patients will not agree to undergo autologous bone harvest at the iliac crest when they know there is a much less invasive option available.
Improving implant fixation
In Japan, Hajime Ohgushi, MD, has been impregnating ceramic total ankle prostheses with stem cells. The devices are then implanted by Y. Takakura, MD, of Nara Medical University, said Ohgushi, leader of the Tissue Engineering Research Group at National Institute of Advanced Industrial Science and Technology (AIST) in Amagasaki City.
Stem cells are expanded in culture after being taken from the patient’s bone marrow. After the implant is placed in the culture, osteoblasts and bone matrix form on it, and then the prosthesis is implanted in the same patient in the hope that the cells will hasten implant fixation. At this point, more than 20 patients have received the tissue-engineered total ankle prosthesis; they have had good results and no complications, Ohgushi told Orthopedics Today.
The initial three cases were followed for more than two years and demonstrated good implant stability. Ohgushi said his center is the first to fabricate such a tissue-engineered total joint replacement. He said they have also treated patients with defects due to bone tumors or osteochondral problems by culturing the cells in calcium-phosphate ceramics.