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.
Stem Cells Transl Med. 2014 Feb;3(2):255-64. doi: 10.5966/sctm.2013-0090. Epub 2013 Dec 16.
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.
成骨不全症（OI）可通过超声在产前识别。间充质干细胞（MSCs）的移植具有改善骨骼损伤的潜力。我们报告了两名接受产前人胎儿 MSC（hfMSC）移植和同供体 MSC 产后增强治疗的 OI 患者的临床病程。我们之前曾报道过 III 型 OI 的产前移植。该患者在 8 岁时再次接受了 2.8×10(6)个同供体 MSC/kg 的移植，导致骨骼低水平植入，并改善了线性生长、活动能力和骨折发生率。一名患有相同突变但未接受 MSC 治疗的婴儿尽管接受了产后双膦酸盐治疗，但在 5 个月时夭折。另一名患有 IV 型 OI 的胎儿也在 31 周妊娠时接受了 30×10(6)个 hfMSC/kg 的移植，在整个妊娠期间和婴儿期都没有发生新的骨折。该患者遵循正常的生长速度，直到 13 个月大，此时纵向长度达到平台期。在 19 个月大时，从同一供体输注了 10×10(6)个 MSC/kg，恢复了她的生长轨迹。两名患者均未对供体 hfMSCs 表现出同种异体反应，也未在移植后表现出任何毒性迹象。我们的发现表明，产前移植同种异体 hfMSCs 在 OI 中似乎是安全的，并且可能具有临床益处，并且用同供体细胞进行再移植是可行的。然而，迄今为止有限的经验意味着无法得出结论，需要进一步研究。
