Neonatal bone marrow transplantation prevents liver disease in a murine model of erythropoietic protoporphyria

Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I

“…16,17 To achieve a more complete donor-derived engraftment, we decided to use a busulfan-mediated preconditioning regimen, which was previously reported to result in high levels of hematopoietic engraftment after nBMT, and a complete hepatic correction in the erythropoietic protoporphyria mouse model. 23 Different from BMT in patients with MPS IH, in whom a significant amount of primary and secondary graft rejection has been observed, 12,35 we here demonstrate that more than 50% of transplanted MPS I mice developed complete, lifelong chimerism, similar to their WT counterparts. No significant acute toxicity was observed in transplanted mice.…”

“…23 Briefly, 1-to 2-day-old pups (Ly5.2 [CD45.2] MPS I or Ly5.2 WT mice) were treated with a single intraperitoneal injection of busulfan (20 mg/kg; Busilvex, Pierre Fabre, Boulogne, France). Eight-to 12-week-old C57BL/6-Ly5.1 (CD45.1) WT donor mice (Charles River) were killed with CO 2 , and the BM was harvested by flushing femurs and tibiae.…”

N-Cadherin/Wnt Interaction Controls Bone Marrow Mesenchymal Cell Fate and Bone Mass During Aging

“…For bone marrow transplantation, 2 days old WT and Cadh2 Tg pups were treated with a single i.p. injection of busulfan (10 mg/kg) (Busilvex, Pierre Fabre, Boulogne, France), and bone marrow was reconstituted by intravenous injection of 10 6 BM cells from WT or Cadh2 Tg donor mice (Duchartre et al, ). Mice (n = 3–6 mice/group) were maintained for 7 weeks for engraftment, and long bones and lumbar vertebrae were isolated and prepared for DEXA or histomorphometric analysis, and long bones and bone marrow were prepared for RNA extraction as described (Duchartre et al, ).…”

Cellular and Gene Therapy for Erythropoietic Porphyrias

“…In another study, the time course of liver disease progression was determined in EPP mice, and it showed that 2-day-old EPP mice accumulate excessive amounts of PPIX in erythrocytes whereas the liver maintains normal PPIX concentration. 71 It was found that the PPIX increase during the first 2 weeks in both erythrocytes and hepatocytes correlates with the onset of liver fibrosis in 12-day-old EPP mice. Surprisingly, early BMT into EPP neonates could fully prevent liver disease occurrence as compared with a late-onset treatment in adult EPP mice.…”