Allogeneic mesoangioblasts give rise to alpha-sarcoglycan expressing fibers when transplanted into dystrophic mice

Maria Guttinger, Elisiana Tafi, Manuela Battaglia, Marcello Coletta, Giulio Cossu

Research output: Contribution to journalArticlepeer-review

Abstract

Cell therapy for muscular dystrophy involves transplantation of either genetically modified autologous cells or normal donor cells that will be rejected unless the host is adequately immune suppressed. The extent of the immune response appears to be mitigated in this case of stem cells, by immune-suppressive and tolerogenic molecules that they release. We previously reported significant morphological and functional amelioration of a mouse model of limb-girdle muscular dystrophy by transplantation of mesoangioblasts. These are vessel-associated stem cells that can be propagated in vitro and differentiate into several types of mesoderm including skeletal muscle. In these experiments, both donor cells and host were syngeneic (C57Bl/6J) and thus possible immune reaction to the donor cells could not be appreciated. To address this question, we transplanted H2-mismatched mesoangioblasts (BalbC) in the same dystrophic mice, and in addition, we treated the host with different pharmacological drugs (rapamycin, IL-10 or both). The results showed that donor cells give rise to fibers that express the mutated gene product (alpha-sarcoglycan) even in the absence of immune suppression; however, the combined action of rapamycin and IL-10 increases the number of alpha-sarcoglycan expressing fibers while reducing the levels of inflammatory cytokines. These results indicate that transplantation of mesoangioblasts into immunologically unrelated host leads to long-term survival of donor cells and this may be further enhanced by appropriate protocols of immune modulation, thus setting the stage for experimentation in large animals and in patients.

Original languageEnglish
Pages (from-to)3872-3879
Number of pages8
JournalExperimental Cell Research
Volume312
Issue number19
DOIs
Publication statusPublished - Nov 15 2006

Keywords

  • Cell therapy
  • Muscle stem cells
  • Muscular dystrophy

ASJC Scopus subject areas

  • Cell Biology

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