Stéphenne Xavier, Najimi Mustapha, Sibille Catherine, Nassogne Marie-Cécile, Smets Françoise, Sokal Etienne M
Laboratoire d'hépatologie Pédiatrique et Transplantation Cellulaire, Département GYPE, Service de Pédiatrie, Université Catholique de Louvain & Cliniques St Luc, Brussels, Belgium.
Gastroenterology. 2006 Apr;130(4):1317-23. doi: 10.1053/j.gastro.2006.01.008.
BACKGROUND & AIMS: Donor cell engraftment with expression of enzyme activity is the goal of liver cell transplantation for inborn errors of liver metabolism with a view to achieving sustained metabolic control.
Sequential hepatic cell transplantations using male and female cells were performed in a 3.5-year-old girl with argininosuccinate lyase deficiency over a period of 5 months. Beside clinical, psychomotor, and metabolic follow-up, engraftment was analyzed in repeated liver biopsies (2.5, 5, 8, and 12 months after first infusion) by fluorescence in situ hybridization for the Y-chromosome and by measurement of tissue enzyme activity.
Metabolic control was achieved together with psychomotor catch-up, changing the clinical phenotype from a severe neonatal one to a moderate late-onset type. The child was no longer hospitalized and was able to attend normal school. Sustained engraftment of male donor liver cells was shown in repeated biopsies, reaching 19% at 8 months and 12.5% at the 12-month follow-up. XXYY tetraploid donor cells were mainly detected during the infusion period (2.5- and 5-month biopsies), whereas in the follow-up 8-month and 1-year biopsies, diploid donor cell subpopulations had become dominant. Moreover, argininosuccinate lyase activity, originally absent, became measurable in 2 different biopsy samples at 8 months, reaching 3% of control activity, indicating in situ metabolic effect and supporting the clinical evolution to a moderate form of the disease.
Liver cell transplantation can achieve donor cell engraftment in humans in a significant proportion, leading to sustained metabolic and clinical control with psychomotor catch-up.
供体细胞植入并表达酶活性是肝细胞移植治疗先天性肝脏代谢缺陷以实现持续代谢控制的目标。
对一名3.5岁精氨酸琥珀酸裂解酶缺乏症女童在5个月内进行了先后使用雄性和雌性细胞的序贯肝细胞移植。除了临床、精神运动和代谢随访外，通过对Y染色体进行荧光原位杂交以及测量组织酶活性，在重复的肝活检中（首次输注后2.5、5、8和12个月）分析植入情况。
实现了代谢控制以及精神运动发育追赶，将临床表型从严重的新生儿型转变为中度迟发型。患儿不再住院，能够正常上学。重复活检显示雄性供体肝细胞持续植入，8个月时达到19%，12个月随访时达到12.5%。XXYY四倍体供体细胞主要在输注期（2.5个月和5个月活检）检测到，而在随访的8个月和1年活检中，二倍体供体细胞亚群占主导。此外，最初不存在的精氨酸琥珀酸裂解酶活性在8个月时在2个不同的活检样本中变得可测量，达到对照活性的3%，表明原位代谢效应并支持疾病临床演变为中度形式。
肝细胞移植可在相当比例的人类患者中实现供体细胞植入，从而实现持续的代谢和临床控制以及精神运动发育追赶。
