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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?

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Author(s):
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Kerkis, Irina [1] ; Ambrosio, Carlos E. [2] ; Kerkis, Alexandre [3] ; Martins, Daniele S. [2] ; Zucconi, Eder [4] ; Fonseca, Simone A. S. [1] ; Cabral, Rosa M. [2] ; Maranduba, Carlos M. C. [1] ; Gaiad, Thais P. [2] ; Morini, Adriana C. [2] ; Vieira, Natassia M. [4] ; Brolio, Marina P. [2] ; Sant'Anna, Osvaldo A. [1] ; Miglino, Maria A. [2] ; Zatz, Mayana [4]
Total Authors: 15
Affiliation:
[1] Inst Butantan, Lab Genet & Imunoquim, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med Vet, Dept Cirurg, BR-05508 Sao Paulo - Brazil
[3] Atividades Vet LTD, Genet Aplicada, Sao Paulo - Brazil
[4] Univ Sao Paulo, Dept Genet & Biol Evolut, Ctr Estudos Genoma Humano, BR-05508 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF TRANSLATIONAL MEDICINE; v. 6, JUL 3 2008.
Web of Science Citations: 101
Abstract

Background: The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression. Methods: Human Immature Dental Pulp Stem Cells (hIDPSC) were transplanted into 4 littermate dogs aged 28 to 40 days by either arterial or muscular injections. Two non-injected dogs were kept as controls. Clinical translation effects were analyzed since immune reactions by blood exams and physical scores capacity of each dog. Samples from biopsies were checked by immunohistochemistry (dystrophin markers) and FISH for human probes. Results and Discussion: We analyzed the cells' ability in respect to migrate, engraftment, and myogenic potential, and the expression of human dystrophin in affected muscles. Additionally, the efficiency of single and consecutive early transplantation was compared. Chimeric muscle fibers were detected by immunofluorescence and fluorescent in situ hybridisation (FISH) using human antibodies and X and Y DNA probes. No signs of immune rejection were observed and these results suggested that hIDPSC cell transplantation may be done without immunosuppression. We showed that hIDPSC presented significant engraftment in GRMD dog muscles, although human dystrophin expression was modest and limited to several muscle fibers. Better clinical condition was also observed in the dog, which received monthly arterial injections and is still clinically stable at 25 months of age. Conclusion: Our data suggested that systemic multiple deliveries seemed more effective than local injections. These findings open important avenues for further researches. (AU)

FAPESP's process: 98/14254-2 - The Human Genome Research Center
Grantee:Mayana Zatz
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC