Bone marrow transplantation in canine mucopolysaccharidosis I. Effects within the central nervous system.
Bone marrow transplantation in canine mucopolysaccharidosis I. Effects within the central nervous system.
复制标题
骨髓移植治疗犬粘多糖贮积症 I. 对中枢神经系统的影响。
DOI：
10.1172/jci112830
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Constantopoulos,G
中科院分区：
文献类型：
--
作者：
Shull,RM;Hastings,NE;Selcer,RR;Jones,JB;Smith,JR;Cullen,WC;Constantopoulos,G
研究人员在5月龄时，将5只患有黏液多糖病的狗移植了表型正常的同窝狗的骨髓。移植后3个月和9个月，对大脑皮层、肝脏和脑脊液进行活检。这些组织的α - l -伊杜糖醛酸酶水平分别为配对供体组织的0.8-7.4、26-45和6.3-14.9%。尽管在两次活检时，受体的大脑和脑脊液中存在相对较低水平的伊杜糖醛酸酶，但脑糖胺聚糖（GAG）的减少与肝脏中观察到的相当。移植犬脑内细胞的超微结构研究显示，与未移植的受影响的同窝对照相比，溶酶体膨胀和储存产物较少。储存的GAG在血管周围的细胞中清除最明显，但也观察到神经元和神经胶质细胞中溶酶体的储存减少。尿GAG排泄也在移植后5个月下降到接近正常水平。图片
Five dogs with mucopolysaccharidosis I, a model of human Hurler/Scheie syndrome, were transplanted with marrow from phenotypically normal littermates at 5 mo of age. At 3 and 9 mo posttransplantation, biopsies of cerebral cortex, liver, and cerebrospinal fluid were obtained. The alpha-L-iduronidase levels in these tissues were 0.8-7.4, 26-45, and 6.3-14.9% of the paired donor tissues, respectively. Although iduronidase was present in relatively low levels in the recipients' brains and cerebrospinal fluid at both biopsy times, reduction in brain glycosaminoglycan (GAG) was comparable to that observed in liver. Ultrastructural studies of cells within the transplanted dogs' brains showed less lysosomal distension and storage product than in affected, nontransplanted, littermate controls. The most marked clearing of stored GAG was in cells surrounding blood vessels, but decreased lysosomal storage in neurons and glial cells was also observed. Urinary GAG excretion also decreased to near normal levels by 5 mo posttransplantation.Images