Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta

Transplantation. 2005 Jun 15;79(11):1607-14. doi: 10.1097/01.tp.0000159029.48678.93.


Background: Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues such as bone, cartilage, and adipose. Adult human leukocyte antigen (HLA)-matched MSC have been used in cellular therapies of bone disorders such as osteogenesis imperfecta, with promising results.

Methods: A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesis imperfecta, underwent transplantation with allogeneic HLA-mismatched male fetal MSC in the 32nd week of gestation. Engraftment analyses of donor cells, immunologic reaction against donor cells, and the well-being of the patient were assessed.

Results: At 9 months of age, on slides stained for osteocalcin or osteopontin, a centromeric XY-specific probe revealed 0.3% of XY-positive cells in a bone biopsy specimen. Whole Y genome fluorescent in situ hybridization staining showed a median of 7.4% Y-positive cells (range, 6.8%-16.6%). Bone histology showed regularly arranged and configurated bone trabeculae. Patient lymphocyte proliferation against donor MSC was not observed in co-culture experiments performed in vitro after MSC injection. Complementary bisphosphonate treatment was begun at 4 months. During the first 2 years of life, three fractures were noted. At 2 years of corrected age, psychomotor development was normal and growth followed the same channel, -5 SD.

Conclusions: The authors' findings show that allogeneic fetal MSC can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Bone and Bones / pathology
  • Collagen / genetics
  • Collagen Type I
  • DNA Primers
  • Female
  • Fetal Tissue Transplantation*
  • Gestational Age
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Infant, Newborn
  • Male
  • Mesoderm
  • Osteogenesis Imperfecta / therapy*
  • Pregnancy
  • Pregnancy Complications / therapy*
  • Stem Cell Transplantation*
  • Transplantation Chimera


  • Collagen Type I
  • DNA Primers
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Collagen