Pre- and Postnatal Transplantation of Fetal Mesenchymal Stem Cells in Osteogenesis Imperfecta: A Two-Center Experience
Pre- and Postnatal Transplantation of Fetal Mesenchymal Stem Cells in Osteogenesis Imperfecta: A Two-Center Experience
复制标题
DOI：
10.5966/sctm.2013-0090
复制
发表时间：
2014-02-01
影响因子：
6
通讯作者：
Chan, Jerry K. Y.
中科院分区：
文献类型：
--
作者：
Gotherstrom, Cecilia;Westgren, Magnus;Chan, Jerry K. Y.
成骨不全 (OI) 可以在产前通过超声识别。间充质干细胞（MSC）移植有可能改善骨骼损伤。我们报告了两名 OI 患者的临床病程，他们接受了产前人类胎儿间充质干细胞 (hfMSC) 移植和产后同供者间充质干细胞强化治疗。我们之前曾报道过 III 型成骨不全症的产前移植。该患者在 8 岁时接受了每公斤 2.8 x 10(6) 个相同供体 MSC 的重新移植，导致骨中的低水平植入，并改善了线性生长、活动能力和骨折发生率。一名未接受间充质干细胞治疗的具有相同突变的婴儿尽管在产后接受了双磷酸盐治疗，但还是在 5 个月时死亡。第二个 IV 型 OI 胎儿在妊娠 31 周时也接受了每公斤 30 x 10(6) hfMSC 的移植，并且在妊娠剩余时间或婴儿期没有出现任何新的骨折。患者一直保持正常的生长速度，直到 13 个月大，此时纵向长度趋于稳定。在 19 个月大时，产后输注了来自同一捐赠者的每公斤 10 x 10(6) MSC，从而恢复了她的生长轨迹。两名患者均未表现出对供体 hfMSC 的同种反应性，也未表现出移植后任何毒性的证据。我们的研究结果表明，成骨不全症中同种异体 hfMSC 的产前移植似乎是安全的，并且可能具有临床益处，并且使用相同供体细胞进行再移植是可行的。然而，迄今为止的经验有限，这意味着不可能得出结论，需要进一步研究。
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 x 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 x 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 x 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.