Related Experiment Videos
Long-term expression of beta-glucuronidase by genetically modified human neural progenitor cells grafted into the
Delphine Buchet1, Ché Serguera, Véronique Zennou
1Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Bat. CERVI, Hôpital de la Pitié-Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France.
Abstract:
Mucopolysaccharidosis type VII (MPS VII) is an inherited disease caused by beta-glucuronidase (beta-glu) deficiency. This deficiency results in the lysosomal accumulation of glycosaminoglycans in all tissues and affects a wide range of organs, including the central nervous system (CNS). Gene transfer is a promising approach to therapy for MPS VII because it allows extensive delivery of the enzyme to the affected tissues. We studied neurotransplantation of primary human cells to supply beta-glucuronidase to the CNS. Human neural progenitor cells (HNPC) were amplified and cotransduced with two lentiviral vectors, one encoding the green fluorescent protein and the other the human beta-glu. We show that these cells strongly expressed both transgenes in culture. When grafted into the mouse striatum, HNPC differentiated into neurons and astrocytes and expressed the two transgenes for at least 6 months. This study therefore paves the way for the treatment of MPS VII by long-term delivery of the appropriate enzyme.
Insights
Gene therapy using human neural progenitor cells (HNPC) offers a potential treatment for Mucopolysaccharidosis type VII (MPS VII). These engineered cells can deliver beta-glucuronidase to the central nervous system (CNS) long-term.
Area of Science:
- Biomedical research
- Gene therapy
- Neuroscience
Background:
- Mucopolysaccharidosis type VII (MPS VII) is a genetic disorder caused by beta-glucuronidase deficiency.
- This deficiency leads to harmful glycosaminoglycan accumulation in tissues, including the central nervous system (CNS).
Purpose of the Study:
- To investigate the potential of neurotransplantation of engineered human neural progenitor cells (HNPC) for treating MPS VII in the CNS.
- To assess the long-term expression and differentiation of transplanted HNPC in a mouse model.
Main Methods:
- Human neural progenitor cells (HNPC) were genetically modified using lentiviral vectors to express human beta-glucuronidase and green fluorescent protein.
- These modified HNPC were transplanted into the mouse striatum.
- Engraftment, differentiation, and transgene expression were monitored over time.
Main Results:
- Transduced HNPC demonstrated robust expression of both transgenes in vitro.
- Following transplantation into the mouse striatum, HNPC differentiated into neurons and astrocytes.
- Sustained expression of the transgenes was observed in the grafted cells for at least 6 months.
Conclusions:
- Neurotransplantation of genetically engineered HNPC is a viable strategy for long-term delivery of beta-glucuronidase to the CNS.
- This approach shows promise for the development of effective therapies for MPS VII.