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.
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: Jennifer M Ryan; Allison R Pettit; Pascale V Guillot; Jerry K Y Chan; Nicholas M Fisk Journal: Stem Cell Rev Rep Date: 2013-08 Impact factor: 5.739
Authors: Elizaveta Kon; Giuseppe Filardo; Alice Roffi; Alessandro Di Martino; Mohammad Hamdan; Laura De Pasqual; Maria Letizia Merli; Maurilio Marcacci Journal: Clin Cases Miner Bone Metab Date: 2012-05-29
Authors: Rafael Moreno; Itziar Martínez-González; Marta Rosal; Marga Nadal; Jordi Petriz; Eduard Gratacós; Josep M Aran Journal: Stem Cells Dev Date: 2011-06-01 Impact factor: 3.272