Low Immunogenicity of Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Derived from Less Immunogenic Somatic Cells

Abstract

The groundbreaking discovery of induced pluripotent stem cells (iPS cells) provides a new source for cell therapy. However, whether the iPS derived functional lineages from different cell origins have different immunogenicity remains unknown. It had been known that the cells isolated from extra-embryonic tissues, such as umbilical cord mesenchymal cells (UMCs), are less immunogenic than other adult lineages such as skin fibroblasts (SFs). In this report, we differentiated iPS cells from human UMCs and SFs into neural progenitor cells (NPCs) and analyzed their immunogenicity. Through co-culture with allologous peripheral blood mononuclear cells (PBMCs), we showed that UMCs were indeed less immunogenic than skin cells to simulate proliferation of PBMCs. Surprisingly, we found that the NPCs differentiated from UMC-iPS cells retained low immunogenicity as the parental UMCs based on the PBMC proliferation assay. In cytotoxic expression assay, reactions in most kinds of immune effector cells showed more perforin and granzyme B expression with SF-NPCs stimulation than that with UMC-NPCs stimulation in PBMC co-culture system, in T cell co-culture system as well. Furthermore, through whole genome expression microarray analysis, we showed that over 70 immune genes, including all members of HLA-I, were expressed at lower levels in NPCs derived from UMC-iPS cells than that from SF-iPS cells. Our results demonstrated a phenomenon that the low immunogenicity of the less immunogenic cells could be retained after cell reprogramming and further differentiation, thus provide a new concept to generate functional lineages with lower immunogenicity for regenerative medicine.

Neural progenitor cells from human induced pluripotent stem cells generated less autogenous immune response

“…Cell viability was examined by trypan blue exclusion staining. Co-culture experiments were carried out as described previously [30,33,34]. Culture volumes of 100 µL per well in a 96-well plate were used, with the ratio of antigen cells to PBMCs kept at 1 : 100.…”

“…NPC differentiation from hESCs and hiPSCs derived from both SFs and UCs was performed as described previously [26,30,35,36]. The typical neural rosettes were blown off and picked out to produce a neural sphere consisting of Figure 1A).…”

Effects of Feeder Cells on Dopaminergic Differentiation of Human Embryonic Stem Cells

“…The HN4 cell line was cultured originally on mixed MEFs and HFFs feeder (MFCs, MEFs: HFFs = 1:1) as previously described (Li et al, 2010; Liu et al, 2013). P96 cell line was cultured originally on HFFs with mTeSR1 medium (STEMCELL Technologies, CA).…”

Building A New Treatment For Heart Failure-Transplantation of Induced Pluripotent Stem Cell-derived Cells into the Heart

“…Though Zhao et al reported immunogenicity of murine iPSCs as compared to ESCs due to the abnormal expression of antigens based on the epigenetic differences between iPSCs and ESCs or mutations in the coding sequences of iPSCs [74], other studies have found only negligible immunogenicity of in vitro -differentiated iPSCs [75-77]. Thus far, the majority of studies have not demonstrated acquired immune reactions against autologous iPSCs and their derivatives.…”