SHED successfully established from an Alagille syndrome patient carrying a heterozygous JAG1 mutation displayed mesenchymal stem cell features but showed reduced population doubling capacity, altered differentiation potency, and damaged in situ potency to form bile duct-like tubular structures in chronically CCl4-injured mouse livers.
Key Findings
Methods
ALGS-SHED were successfully isolated from a deciduous tooth of an Alagille syndrome patient with a heterozygous JAG1 mutation using the colony-forming unit-fibroblast (CFU-F) method.
Isolation was performed using the CFU-F method from an ALGS patient carrying a heterozygous JAG1mut mutation.
ALGS-SHED were compared against healthy donor-derived control SHED (CONT-SHED).
This represents the first reported patient-derived SHED line from an ALGS patient.
The study notes that while many pluripotent stem cells are well established, no patient-derived SHED had previously been developed for ALGS.
Results
ALGS-SHED displayed core mesenchymal stem cell features including CFU-F formation, appropriate immunophenotype, and multipotent differentiation capacity into adipocytes, chondrocytes, and osteoblasts.
Mesenchymal stem cell identity was confirmed by CFU-F formation assay.
Immunophenotype characteristic of mesenchymal stem cells was confirmed.
Multipotency was demonstrated by successful differentiation into adipocytes, chondrocytes, and osteoblasts.
These features confirmed ALGS-SHED as bona fide mesenchymal stem cells despite carrying the JAG1 mutation.
Results
ALGS-SHED showed reduced population doubling capacity compared to control SHED.
Reduced population doubling capacity was identified as a distinguishing characteristic of ALGS-SHED versus CONT-SHED.
This finding suggests that the heterozygous JAG1 mutation affects the proliferative capacity of the stem cells.
Population doubling capacity was measured and compared between ALGS-SHED and CONT-SHED.
Results
ALGS-SHED exhibited induced (enhanced) chondrogenic potency and diminished osteogenic potency relative to control SHED.
Chondrogenic differentiation potency was increased in ALGS-SHED compared to CONT-SHED.
Osteogenic differentiation potency was decreased in ALGS-SHED compared to CONT-SHED.
These alterations in differentiation bias suggest that the JAG1 mutation affects the balance of mesenchymal lineage commitment.
The opposing directions of change in chondrogenic versus osteogenic potency indicate a shift in differentiation equilibrium rather than global suppression.
Results
ALGS-SHED and control SHED showed similar hepatic differentiation potency in vitro.
Hepatic potency was assessed and found to be comparable between ALGS-SHED and CONT-SHED.
This similarity in hepatic differentiation capacity in vitro contrasted with the in vivo functional differences observed.
The finding suggests that the JAG1 mutation does not globally impair hepatic lineage commitment potential under standard differentiation conditions.
Results
ALGS-SHED showed damaged in situ potency to form bile duct-like tubular structures in the livers of chronically CCl4-injured mice.
In vivo assessment was performed using a chronic CCl4 liver injury mouse model.
ALGS-SHED were impaired in their ability to form bile duct-like tubular structures within the injured liver environment.
This in vivo functional deficit contrasted with the similar in vitro hepatic potency between ALGS-SHED and CONT-SHED.
The finding implicates JAG1 mutation in disrupting the bile duct formation capacity that is clinically relevant to Alagille syndrome pathology.
Conclusions
The authors propose that ALGS-SHED may represent a potential model for studying Alagille syndrome involving a JAG1 mutation.
ALGS-SHED recapitulated disease-relevant features including impaired bile duct-like structure formation.
The model captures a heterozygous JAG1 mutation consistent with the autosomal dominant inheritance pattern of ALGS.
SHED represent a patient-accessible, minimally invasive source of stem cells through naturally exfoliated deciduous teeth.
The authors suggest this model could be used to study ALGS pathophysiology involving JAG1 mutations.
What This Means
This research suggests that stem cells can be successfully harvested from baby teeth (deciduous teeth) of a child with Alagille syndrome, a rare genetic disorder that primarily affects the liver and bile ducts and is caused by mutations in a gene called JAG1. The researchers collected these stem cells — called SHED (stem cells from human exfoliated deciduous teeth) — from a patient carrying one faulty copy of the JAG1 gene, and compared them to SHED from a healthy donor. They found that while the patient's SHED behaved like normal stem cells in many ways, they also showed meaningful differences: they divided more slowly, were better at forming cartilage cells but worse at forming bone cells, and — critically — were less able to form bile duct-like structures inside the livers of mice with liver damage.
The bile duct finding is particularly significant because the hallmark problem in Alagille syndrome is a shortage of bile ducts in the liver, which impairs the liver's ability to drain bile and leads to serious liver disease. The fact that SHED from the Alagille patient were less capable of contributing to bile duct formation in a living organism mirrors what happens in the disease itself, even though the cells appeared normal in lab dish tests of liver-making ability. This gap between in-the-dish and in-the-body behavior highlights why animal model testing matters.
This research suggests that baby teeth from children with Alagille syndrome — which would otherwise simply be discarded — could serve as a valuable and ethically straightforward source of patient-specific stem cells for studying this rare disease. These ALGS-SHED could be used as a research tool to better understand how JAG1 mutations cause bile duct problems and potentially to test future treatments, without requiring invasive procedures from the patient.
Uchida Y, Sonoda S, Dai L, Yoshimaru K, Fukumoto S, Yamaza H, et al.. (2026). Characterization of stem cells from exfoliated deciduous teeth from a patient with Alagille syndrome carrying a JAG1 mutation.. Pediatric surgery international. https://doi.org/10.1007/s00383-026-06620-2