Subcutaneous implantation of microencapsulated cells overexpressing α-L-iduronidase for mucopolysaccharidosis type I treatment.
Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of α-L-iduronidase (IDUA), resulting in accumulation of glycosaminoglycans (GAG) in lysosomes. Microencapsulation of recombinant cells is a promising gene/cell therapy approach that could overcome the limitations of the current available treatments. In the present study we produced alginate-poly-L-lysine-alginate (APA) microcapsules containing recombinant cells overexpressing IDUA, which were implanted in the subcutaneous space of MPS I mice in order to evaluate their potential effect as a treatment for this disease. APA microcapsules enclosing genetically modified Baby Hamster Kidney cells overexpressing IDUA were produced and implanted in the subcutaneous space of 4-month-old MPS I mice (Idua-/-). Treatment was performed using two cell concentrations: 8.3 × 107and 8.3 × 106cells/mL. Untreated MPS I and normal mice were used as controls. Microcapsules were retrieved and analyzed after treatment. Increased IDUA in the liver, kidney and heart was detected 24 h postimplantation. After 120 days, higher IDUA activity was detected in the liver, kidney and heart, in both groups, whereas GAG accumulation was reduced only in the high cell concentration group. Microcapsules analysis showed blood vessels around them, as well as inflammatory cells and a fibrotic layer. Microencapsulated cells were able to ameliorate some aspects of the disease, indicating their potential as a treatment. To achieve better performance of the microcapsules, improvements such as the modulation of inflammatory response are suggested.
Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Valeska
V
Lizzi Lagranha
Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Postgraduate Program in Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Barbara
B
Zambiasi Martinelli
Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Postgraduate Program in Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Guilherme
G
Baldo
Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Giuseppe
G
Ávila Testa
Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Talita
T
Giacomet de Carvalho
Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.|Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Postgraduate Program in Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Roberto
R
Giugliani
Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. umatte@hcpa.edu.br.|Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. umatte@hcpa.edu.br.
Ursula
U
Matte
D000464:Alginates / Q000737:chemistry; D000818:Animals; D002214:Capsules / Q000737:chemistry; D002460:Cell Line; D006224:Cricetinae; D004339:Drug Compounding; D006025:Glycosaminoglycans / Q000737:chemistry; D007068:Iduronidase / Q000737:chemistry*; D007107:Immune System; D007249:Inflammation; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects; D008247:Lysosomes / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008059:Mucopolysaccharidosis I / Q000188:drug therapy*; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D014018:Tissue Distribution
D000464:Alginates; D002214:Capsules; D006025:Glycosaminoglycans; D011994:Recombinant Proteins; C051546:alginate-polylysine-alginate; D011107:Polylysine; D007068:Iduronidase