Functional Evaluation of Mesenchymal Stem Cells Derived from Canine Induced Pluripotent Stem Cells

ABSTRACT: Comparison of gene expression profiles of canine induced pluripotent stem cells (iPSC) and iPS derived mesenchymal stem cells (iMSC) by microarray Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell and dendritic cell activation in vitro. Currently, most MSC for clinical usage are derived from adipose or bone marrow tissues from younger donors, in part due to ease of procurement and to the superior immune modulatory activity of young MSC. However, use of MSC from multiple unrelated donors makes it difficult to standardize MSC cellular products with uniform immune modulatory properties. One solution to this problem is the use of MSC derived from induced pluripotent stem cells (iPSC), as iPSC-derived MSC have nearly unlimited proliferative potential and exhibit in vitro phenotypic stability. Given the value of dogs as a spontaneous disease model for pre-clinical evaluation of stem cell therapeutics, we investigated the functional properties of canine iPSC-derived MSC (iMSC), including their immune modulatory properties and their potential for teratoma formation. We found that canine iMSC downregulated expression of pluripotency genes and appeared morphologically similar to conventional MSC. Importantly, iMSC retained a stable phenotype even after multiple passages, did not form teratomas when inoculated in immune deficient mice, and did not induce tumor formation in purpose-bred dogs following systemic injection. The immune potency of iMSC was similar to that of adipose and bone-marrow derived MSC with respect to suppression of T cell and DC activation. We concluded therefore that iMSC were phenotypically stable, immunologically potent, and safe with respect to tumor formation, and represented an important new source of cells for therapeutic modulation of inflammatory disorders.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE94081 | GEO | 2017/01/26

SECONDARY ACCESSION(S): PRJNA368749

REPOSITORIES: GEO