PMID- 15940052 OWN - NLM STAT- MEDLINE DCOM- 20050728 LR - 20231024 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 79 IP - 11 DP - 2005 Jun 15 TI - Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta. PG - 1607-14 AB - 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. FAU - Le Blanc, Katarina AU - Le Blanc K AD - Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. Katarina.leblanc@medhs.ki.se FAU - Gotherstrom, Cecilia AU - Gotherstrom C FAU - Ringden, Olle AU - Ringden O FAU - Hassan, Moustapha AU - Hassan M FAU - McMahon, Robert AU - McMahon R FAU - Horwitz, Edwin AU - Horwitz E FAU - Anneren, Goran AU - Anneren G FAU - Axelsson, Ove AU - Axelsson O FAU - Nunn, Janice AU - Nunn J FAU - Ewald, Uwe AU - Ewald U FAU - Norden-Lindeberg, Solveig AU - Norden-Lindeberg S FAU - Jansson, Monika AU - Jansson M FAU - Dalton, Ann AU - Dalton A FAU - Astrom, Eva AU - Astrom E FAU - Westgren, Magnus AU - Westgren M LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Collagen Type I) RN - 0 (DNA Primers) RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DRB1 Chains) RN - 9007-34-5 (Collagen) SB - IM MH - Adult MH - Biopsy MH - Bone and Bones/pathology MH - Collagen/genetics MH - Collagen Type I MH - DNA Primers MH - Female MH - *Fetal Tissue Transplantation MH - Gestational Age MH - HLA-DR Antigens/genetics MH - HLA-DRB1 Chains MH - Humans MH - In Situ Hybridization, Fluorescence MH - Infant MH - Infant, Newborn MH - Male MH - Mesoderm MH - Osteogenesis Imperfecta/*therapy MH - Pregnancy MH - Pregnancy Complications/*therapy MH - *Stem Cell Transplantation MH - Transplantation Chimera EDAT- 2005/06/09 09:00 MHDA- 2005/07/29 09:00 CRDT- 2005/06/09 09:00 PHST- 2005/06/09 09:00 [pubmed] PHST- 2005/07/29 09:00 [medline] PHST- 2005/06/09 09:00 [entrez] AID - 00007890-200506150-00021 [pii] AID - 10.1097/01.tp.0000159029.48678.93 [doi] PST - ppublish SO - Transplantation. 2005 Jun 15;79(11):1607-14. doi: 10.1097/01.tp.0000159029.48678.93.