Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts.
BACKGROUND
Hypophosphatasia (HPP) is a rare, heritable, metabolic bone disease due to deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. The infantile form features severe rickets often causing death in the first year of life from respiratory complications. There is no established medical treatment. In 1997, an 8-month-old girl with worsening and life-threatening infantile HPP improved considerably after marrow cell transplantation.


OBJECTIVE
Our aim was to better understand and to advance these encouraging transplantation results.


METHODS
In 1999, based on emerging mouse transplantation models involving implanted donor bone fragments as well as osteoblast-like cells cultured from bone, we treated a 9-month-old girl suffering a similar course of infantile HPP.


RESULTS
Four months later, radiographs demonstrated improved skeletal mineralization. Twenty months later, PCR analysis of adherent cells cultured from recipient bone suggested the presence of small amounts of paternal (donor) DNA despite the absence of hematopoietic engraftment. This patient, now 8 yr old (7 yr after transplantation), is active and growing, and has the clinical phenotype of the more mild, childhood form of HPP.


CONCLUSIONS
Cumulative experience suggests that, after immune tolerance, donor bone fragments and marrow may provide precursor cells for distribution and engraftment in the skeletal microenvironment in HPP patients to form tissue-nonspecific isoenzyme of alkaline phosphatase-replete osteoblasts that can improve mineralization.
Cahill
Richard A
RA
Pediatric Research Institute, Cardinal Glennon Children's Hospitals, St. Louis, Missouri 63110, USA.
Wenkert
Deborah
D
Perlman
Sharon A
SA
Steele
Ann
A
Coburn
Stephen P
SP
McAlister
William H
WH
Mumm
Steven
S
Whyte
Michael P
MP
D000469:Alkaline Phosphatase / Q000097:blood / Q000235:genetics; D016026:Bone Marrow Transplantation; D016025:Bone Transplantation; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D003582:Cytogenetics; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D007014:Hypophosphatasia / Q000150:complications / Q000628:therapy*; D007223:Infant; D007717:Knee / Q000000981:diagnostic imaging; D010006:Osteoblasts / Q000637:transplantation*; D011859:Radiography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology
D004247:DNA; D000469:Alkaline Phosphatase