title: Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience.
abstract: Osteogenesis imperfecta (OI) can be recognized prenatally with ultrasound. Transplantation of mesenchymal stem cells (MSCs) has the potential to ameliorate skeletal damage. We report the clinical course of two patients with OI who received prenatal human fetal MSC (hfMSC) transplantation and postnatal boosting with same-donor MSCs. We have previously reported on prenatal transplantation for OI type III. This patient was retransplanted with 2.8 × 10(6) same-donor MSCs per kilogram at 8 years of age, resulting in low-level engraftment in bone and improved linear growth, mobility, and fracture incidence. An infant with an identical mutation who did not receive MSC therapy succumbed at 5 months despite postnatal bisphosphonate therapy. A second fetus with OI type IV was also transplanted with 30 × 10(6) hfMSCs per kilogram at 31 weeks of gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. The patient followed her normal growth velocity until 13 months of age, at which time longitudinal length plateaued. A postnatal infusion of 10 × 10(6) MSCs per kilogram from the same donor was performed at 19 months of age, resulting in resumption of her growth trajectory. Neither patient demonstrated alloreactivity toward the donor hfMSCs or manifested any evidence of toxicities after transplantation. Our findings suggest that prenatal transplantation of allogeneic hfMSCs in OI appears safe and is of likely clinical benefit and that retransplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive and that further studies are required.
authors.affiliation: Division of Obstetrics and Gynecology, Center for Hematology and Regenerative Medicine, Department of Women's and Children's Health and Neuro-pediatric Unit, and Hematology Center, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Obstetrics and Gynecology and Division of Medical Genetics, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan; Experimental Fetal Medicine Group, Department of Obstetrics and Gynecology, and Department of Pediatrics, Yong Loo Lin School of Medicine and National University of Singapore, Singapore; Departments of Pathology and Medicine (Medical Genetics), University of Washington, Seattle, Washington, USA; Department of Genetics, Children's Hospital of Eastern Ontario and Department of Pediatrics, University of Ottawa, Ottawa, Canada; Orthopedic Unit, Uppsala University Hospital, Uppsala, Sweden; Women's and Children's Health, Uppsala University, Uppsala, Sweden; Centre for Clinical Research, University of Queensland, Brisbane, Australia; Department of Reproductive Medicine, Women's and Children's Hospital, Singapore; Cancer and Stem Cell Biology, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Götherström
authors.forename: Magnus
authors.initials: M
authors.lastname: Westgren
authors.forename: S W Steven
authors.initials: SW
authors.lastname: Shaw
authors.forename: Eva
authors.initials: E
authors.lastname: Aström
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.forename: Peter H
authors.initials: PH
authors.lastname: Byers
authors.forename: Citra N Z
authors.initials: CN
authors.lastname: Mattar
authors.forename: Gail E
authors.initials: GE
authors.lastname: Graham
authors.forename: Jahan
authors.initials: J
authors.lastname: Taslimi
authors.forename: Uwe
authors.initials: U
authors.lastname: Ewald
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
authors.forename: Allen E J
authors.initials: AE
authors.lastname: Yeoh
authors.forename: Ju-Li
authors.initials: JL
authors.lastname: Lin
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Cheng
authors.forename: Mahesh
authors.initials: M
authors.lastname: Choolani
authors.forename: Katarina
authors.initials: K
authors.lastname: Le Blanc
authors.forename: Jerry K Y
authors.initials: JK
authors.lastname: Chan
mesh_terms: D001846:Bone Development; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000628:therapy*; D005333:Fetus / Q000166:cytology*; D005838:Genotype; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics / Q000628:therapy*; D010375:Pedigree; D011247:Pregnancy; D011859:Radiography
keywords: Cell therapy; In utero transplantation; Mesenchymal stem cells; Mesenchymal stromal cells; Osteogenesis imperfecta; Prenatal transplantation