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

Abstract

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.

• Authors: Katarina Le Blanc, Cecilia Götherström, Olle Ringdén, Moustapha Hassan, Robert McMahon, Edwin Horwitz, Göran Anneren, Ove Axelsson, Janice Nunn, Uwe Ewald, Solveig Nordén-Lindeberg, Monika Jansson, Ann Dalton, Eva Aström, Magnus Westgren
• Journal: Transplantation (Transplantation) Vol. 79 Issue 11 Pg. 1607-14 (Jun 15 2005) ISSN: 0041-1337 [Print] United States
• PMID: 15940052 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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