In years to come, people who suffer severely traumatizedor diseased bones or joints may well have 30 whiterabbits to thank for their good-as-new replacements.
These animals held center stage Wednesday morning inNew Orleans at the 1995 Clinical Congress of theAmerican College of Surgeons. They demonstrated theability of a recombinant growth factor, osteogenicprotein, to create new bone and gristle out of stem cellsand a flap of muscle.
David Brown, a resident in plastic and reconstructivesurgery at Washington University School of Medicine, ofSt. Louis, told the orthopedics session of the congresshow he and his colleagues regenerated bone and cartilagein rabbit shoulder joints.
First, they surgically removed two-thirds of the humerus(upper arm bone) from all 30 test animals, and replaced itwith a matrix of powdered, freeze-dried alloplastic bone(taken from other rabbits). This is standard operatingprocedure for such bone grafts. Then they divided the 30animals into four groups:
* Five controls received no further treatment.
* Five others got 10 milligrams of osteogenic protein(OP-1) mixed into the matrix.
* Another 10 animals also had a flap of their own musclethreaded inside the bone's marrow-cavity scaffolding.Their muscle provided a source of blood supply, andexposed the inner surface of the graft to living tissue.
* And a final cohort of 10 got OP-1-treated matrix, withall of the muscle flap inside the marrow itself.
OP-1 Regenerated Bone, Restored Joint Motion
One month later, Brown told his orthopedic audience,OP-1-treated rabbits in groups 2 and 4 had regained 70 to75 percent of their joints' range of motion, with nofractures. "The articular surface showed newly generatedarticular cartilage [with] florid new bone formation onboth sides of the cortex." At six months, motion rangehad declined to 50 percent, but "the muscle wascompletely transformed into bone marrow, and livearticular cartilage was present on the articular surface."
At the opposite extreme, in the first group, whichreceived only standard treatment, "all the shoulderjoints," Brown reported, "were stiff and contracted, andfour out of five grafts had cortical [outer bone layer]fractures."
Osteogenic protein, [OP-1] Brown explained, "is a bonemorphogenetic protein that is capable of inducing theproliferation and transformation of mesenchymal cells[precursors of blood, bone and cartilage] present intissues such as muscle into bone and cartilage."
Group 4's muscle flap, Brown added, "increases the localsupply of mesenchymal cells capable of responding to theOP-1 stimulus."
Brown, whose principal co-author is WashingtonUniversity surgeon Roger Khouri, concluded hispresentation by observing, "Under the influence of OP-1 .. . host stem cells are induced to differentiate into normalosteocytes and chondrocytes, to reconstitute a functioninghemijoint."
Rabbits Now, People (Much) Later
This combined treatment, he suggested, "may provide amore physiologic alternative to the current alloplasticjoint replacements."
Khouri, who devised the OP-1-based technique, told theCongress press office that "it will take four to five yearsbefore the process may be tried in human beings." Oncethe procedure is clinically proven and approved, headded, "one can conceive of reconstructive surgerydepartments maintaining a supply of freeze-dried donorbone grafts, rather than metal or plastic ones."
Then, Khouri said, "Whenever a young cancer or traumapatient needed joint replacement, we would install thispiece of activated dried bone tissue, knowing that withina few weeks it will turn into a live piece of bone, and actjust as if it were the patient's own bone."
Khouri is a scientific collaborator of CreativeBioMolecules Inc., of Hopkinton, Mass. Its vice-presidentof corporate development, Stephanie Marrus, toldBioWorld Today that the company "was the first toidentify the morphogenetic protein, OP-1, and clone itsgene."
Such morphogens, she explained, "stimulate theformation of tissues in the body by signalingunspecialized stem cells to commit to cells with aparticular function."
In partnership with Creative BioMolecules, Stryker Corp.,of Kalamazoo, Mich., currently is conducting a pivotalclinical trial of OP-1 in the U.S. to regenerate bone tissuein tibial (shin-bone) fractures that fail to knit. Strykeranticipates completing patient accrual to this device study(equivalent to a Phase III drug trial) by the end of 1995.
Marrus observed that "OP-1 is the first recombinanthuman protein to enter clinical trials for the repair oforthopedic defects." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.