title: Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts.
abstract: 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.
authors.affiliation: Pediatric Research Institute, Cardinal Glennon Children's Hospitals, St. Louis, Missouri 63110, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cahill
authors.forename: Deborah
authors.initials: D
authors.lastname: Wenkert
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Perlman
authors.forename: Ann
authors.initials: A
authors.lastname: Steele
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Coburn
authors.forename: William H
authors.initials: WH
authors.lastname: McAlister
authors.forename: Steven
authors.initials: S
authors.lastname: Mumm
authors.forename: Michael P
authors.initials: MP
authors.lastname: Whyte
mesh_terms: 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
chemical_list: D004247:DNA; D000469:Alkaline Phosphatase