Clinical study of HAES transplantation in patients with neonatal onset urea cycle disorder

General Information

Summary HAES is derived from human ES cells and directed to differentiate to cells with ammonia metabolism capacity. HAES transplantation is expected as an effective bridging therapy to liver transplantation for patients with urea cycle disorder. This study is conducted to assess the safety and efficacy of HAES transplantation for the neonatal onset patients who have difficulty in instant liver transplantation surgery due to low body weight (6 kg or less).
Clinical trials phase Phases 1/2
Start date (estimated) 2018-04-30
End date (estimated) 2022-09-30
Clinical feature
Label urea cycle disorder
Link http://purl.obolibrary.org/obo/DOID_9267
Description An amino acid metabolic disorder that involves a deficiency of one of the enzymes in the urea cycle which is responsible for removing ammonia from the blood stream.

Administrative Information

ICTRP weblink https://trialsearch.who.int/Trial2.aspx?TrialID=JPRN-JMA-IIA00412
Other study identifiers
Name JMA-IIA00412
Description J​M​A​C​C​T​ ​I​D
Source weblink https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRE02_04/JMACTRE02_04.aspx?kbn=3&seqno=9141
Public contact
Email f​u​k​u​h​a​r​a​-​y​s​@​n​c​c​h​d​.​g​o​.​j​p
Public email f​u​k​u​h​a​r​a​-​y​s​@​n​c​c​h​d​.​g​o​.​j​p
First name Y​a​s​u​y​u​k​i
Last name F​u​k​u​h​a​r​a
Phone +81-3-3416-0181
Fax +​8​1​-​3​-​3​4​1​6​-​2​2​2​2
City Tokyo
Country
Japan
Address freetext 2​-​1​0​-​1​ ​O​k​u​r​a​ ​S​e​t​a​g​a​y​a​ ​T​o​k​y​o​ ​1​5​7​-​8​5​3​5
Sponsors National center for child health and development

Cells

Which differentiated cell type is used
Label hepatocyte
Link http://purl.obolibrary.org/obo/CL_0000182
Description The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Majority of cell population of liver, polygonal in shape, arranged in plates or trabeculae between sinusoids; may have single nucleus or binucleated.; This extended description was generated by ChatGPT and reviewed by the CellGuide team, who added references, and by the CL editors, who approved it for inclusion in CL. It may contain information that applies to only to some subtypes and species, and so should not be considered definitional. Hepatocytes are the major cell type constituting 70-80% of the liver's cytoplasmic mass, playing crucial roles in maintaining the body's metabolic homeostasis. Dimensions of mature hepatocytes typically range from 20 to 30 μm in humans, but size may vary depending on their location within the liver lobule. Hepatocytes are characterized by high biosynthetic, enzymatic, and endocytic activity. They contain abundant mitochondria, smooth and rough endoplasmic reticulum, peroxisomes, lysosomes, and a large nucleus that is often binucleate. The liver consists of three zones - the periportal Zone 1, midzone 2, and pericentral Zone 3 - which have differential nutrient and oxygen status, and damage susceptibility; hepatocytes in the different zones show signifcant functional heterogeneity ('hepatocyte functional zonation'). Hepatocytes are involved in a multitude of critical functions including the metabolism of lipids, carbohydrates, and proteins, the synthesis of serum proteins (e.g., albumin, transferrin, and lipoproteins), the detoxification and excretion of endogenous and exogenous substances, the storage of vitamins and minerals, and the production and secretion of bile. Heterocytes demonstrate a remarkable regenerative capacity, which enables the liver to recover from injury and loss of tissue mass. Notably, hepatocytes perform biotransformation with both phase I and phase II enzymes, which modify drugs, xenobiotics, and various substances for elimination from the body. Phase I enzymes, such as cytochrome P450, catalyze both oxidative and reductive reactions of many xenobiotics; many of the products of phase I enzymes are substrates for the phase II enzymes, which catalyze conjugation reactions. Alterations in hepatocyte function have significant implications for overall human health and disease. Certain conditions, such as hepatitis, cirrhosis, and liver cancer, can profoundly affect hepatocyte structure and function, thereby disrupting the liver's ability to perform its vital roles within the body. As the primary site for drug metabolism, changes in hepatocyte function can also impact the effectiveness and toxicity of pharmaceuticals. The regenerative ability of hepatocytes makes them valuable cells for liver regenerative medicine and bioartificial liver support systems, and their study has provided significant insights into liver biology and disease.; Hepatocytes are reportedly MHC Class I-positive and MHC Class II-positive.

Recruitment

Recruitment Status Recruiting
Comment recruitment status Performed number of subjects: 2
Estimated number of participants 5