Nature Medicine
5, 309 - 313 (1999)
doi:10.1038/6529
Transplantability and therapeutic effects of bone marrow-derived mesenchymal
cells in children with osteogenesis imperfectaEdwin M. Horwitz1, Darwin J. Prockop2, Lorraine A. Fitzpatrick3, Winston W. K. Koo4, Patricia L. Gordon1, Michael Neel1, Michael Sussman5, Paul Orchard6, Jeffrey C. Marx1, Reed E. Pyeritz2
& Malcolm K. Brenner11
Cell and Gene Therapy Program, St. Jude Children's
Research Hospital, 332 North Lauderdale, Memphis,
Tennessee 38105, USA
2
Allegheny University of the Health Sciences,
15th and Vine Streets, Philadelphia,
Pennsylvania 19102, USA
3
Mayo Clinic, 200 First Street SW, Rochester,
Minnesota 55905, USA
4
Wayne State University, 4707 St. Antoine
Boulevard, Detroit, Michigan 48201, USA
5
Shriner's Hospital for Children, 3101
SW Sam Jackson Park Road, Portland, Oregon
97201, USA
6
University of Minnesota, 420 Delaware
Street, SE, Minneapolis, Minnesota 55455,
USA
Correspondence should be addressed to Edwin M. Horwitz In principle, transplantation of mesenchymal progenitor cells would attenuate
or possibly correct genetic disorders of bone, cartilage and muscle, but clinical
support for this concept is lacking. Here we describe the initial results
of allogeneic bone marrow transplantation in three children with osteogenesis
imperfecta, a genetic disorder in which osteoblasts produce defective type
I collagen, leading to osteopenia, multiple fractures, severe bony deformities
and considerably shortened stature. Three months after osteoblast engraftment
(1.5−2.0% donor cells), representative specimens of trabecular bone
showed histologic changes indicative of new dense bone formation. All patients
had increases in total body bone mineral content ranging from 21 to 29 grams
(median, 28), compared with predicted values of 0 to 4 grams (median, 0) for
healthy children with similar changes in weight. These improvements were associated
with increases in growth velocity and reduced frequencies of bone fracture.
Thus, allogeneic bone marrow transplantation can lead to engraftment of functional
mesenchymal progenitor cells, indicating the feasibility of this strategy
in the treatment of osteogenesis imperfecta and perhaps other mesenchymal
stem cell disorders as well.
|
