Subcutaneous implantation of microencapsulated cells overexpressing α-L-iduronidase for mucopolysaccharidosis type I treatment

  • Valeska Lizzi Lagranha
  • Barbara Zambiasi Martinelli
  • Guilherme Baldo
  • Giuseppe Ávila Testa
  • Talita Giacomet de Carvalho
  • Roberto Giugliani
  • Ursula Matte
Clinical Applications of Biomaterials Original Research
Part of the following topical collections:
  1. Clinical Applications of Biomaterials


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 × 107 and 8.3 × 106 cells/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.

Graphical Abstract

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Hematopoietic Stem Cell Transplantation Enzyme Replacement Therapy Recombinant Cell High Cell Concentration Baby Hamster Kidney Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





Enzyme replacement therapy




Hematopoietic stem cell transplantation




Lysosomal storage disorder


Mucopolysaccharidosis type I


Recombinant BHK to overexpress IDUA



The authors are grateful to CNPq, CAPES and FIPE-HCPA for the financial support that allowed this research.

Compliance with ethical standards

Conflict of interest

The authors declare no competing conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Valeska Lizzi Lagranha
    • 1
    • 2
  • Barbara Zambiasi Martinelli
    • 1
    • 3
  • Guilherme Baldo
    • 1
    • 2
    • 4
  • Giuseppe Ávila Testa
    • 1
  • Talita Giacomet de Carvalho
    • 1
    • 2
  • Roberto Giugliani
    • 1
    • 2
    • 3
  • Ursula Matte
    • 1
    • 2
  1. 1.Gene Therapy Center, Hospital de Clínicas de Porto AlegrePorto AlegreBrazil
  2. 2.Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Postgraduate Program in Biochemistry, Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Postgraduate Program in Physiology, Universidade Federal do Rio Grande do SulPorto AlegreBrazil

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