FETAL STEM CELL TRANSPLANTATION FOR ALPHA THALASSEMIA

12-13周时移植异基因骨髓干细胞的人 年龄会形成稳定而持久的嵌合体。这一假设 起源于观察到T细胞不会从 人类胎儿胸腺直到怀孕14周，以及这一发现 移植了干细胞的动物，在拥有T细胞之前就会发育 特异性免疫耐受。因此，可能会更正一个 干细胞移植前先天疾病的范围 不可逆转的损害。我们对RFA的回应集中在人类身上，因为 这是我们拥有特殊优势的领域。纯合子胎儿 对于阿尔法地中海贫血(一种导致胎儿积水的血红蛋白病)， 由夏威夷的Genetics服务使用HBA链特定的 聚合酶链式反应在8-10周绒毛活检中的应用 怀孕了。有受影响胎儿的家庭将被提供进入主题 符合特定标准，并在12周前进入加州大学圣迭戈分校的CRC 怀孕的感觉。骨髓将从合适的捐赠者那里提取，经过处理 耗尽T细胞并富含干细胞，然后注射到 12-13周患胎儿脐静脉。怀孕将是 在第26周期间，由ECHO每隔7天监测一次。一份胎儿血样 (FBS)将在19-20周内获得，并进行Hb型和 用聚合酶链式反应检测嵌合体。Hb含量为10g/dL的胎儿将输注 红血球堆积。胎儿血液样本将在26-28周内采集 从存活的胎儿身上检测出Hb型，嵌合体和同种异体抗原- 特定容忍度。不会尝试对胎儿进行进一步治疗 在这一点上不是嵌合体。嵌合体胎儿将得到支持 根据需要通过34-36周，然后交付。幸存的新生儿 将重新检测红系和白细胞系列的嵌合体， 以及耐受性或同种异体反应的程度。是谁的胎儿 36-34周的输血依赖者将被重新移植到 新生儿期。我们的研究将检验我们的潜在假设，并将 因此产生了关于哪些基因工程胎儿移植物的数据 细胞可能基于。

Humans grafted with allogeneic bone marrows stem cells at 12-13 weeks of age will develop stable and long lasting chimerism. This hypothesis derives from the observation that T cells do not peripheralize from the human fetal thymus until 14 weeks of gestation, together with the finding that animals grafted with stem cells, before they have T cells develop specific immunologic tolerance. Thus, it may be possible to correct a range of congenital disorders by stem cell transplant prior to irreversible damage. Our response to the RFA focuses on humans because this is the area in which we have specific strengths. Fetuses homozygous for alpha thalassemia (a hemoglobinopathy causing fetal hydrops) will be identified by the Genetics service in Hawaii using an Hba chain specific PCR applied to chorionic villous biopsies obtained at 8-10 weeks gestation. Families with affected fetuses will be offered entry subject to specific criteria and admitted to the CRC at UCHSC by the 12th week of gestation. Marrow will be drawn from an appropriate donor, processed to deplete T cells and enrich for stem cells and then injected into the umbilical vein of affected fetuses at 12-13 weeks. Pregnancies will be monitored every 7 days through week 26 by ECHO. A fetal blood sample (FBS) will be obtained at 19-20 weeks and tested for Hb type and for chimerism by PCR. Fetuses with <10 g/dL of Hb will be transfused with packed red cells. A fetal blood sample will be obtained at 26-28 weeks from surviving fetuses and tested for Hb type, chimerism and alloantigen- specific tolerance. No further treatment will be attempted for fetuses who are not chimeric at this point. Chimeric fetuses will be supported as required through 34-36 weeks and then delivered. Surviving newborns will be retested for chimerism in the erythroid and white cell series, along with the degree of tolerance or alloreactivity. Fetuses who were transfusion dependent at 36-34 weeks will be retransplanted in the newborn period. Our studies will test our underlying hypothesis and will therefore generate data on which fetal grafts of genetically engineered cells might be based.