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.
Highlights
The successful establishment of human embryonic stem cells proved a decisive turning point in biomedical science, providing a renewable source of various cell types for human cell therapy [1]. hES cells derived from early blastocysts are pluripotent and able to differentiate into all cell types present in the body [1,2]
We examined the proliferation of this mixed cell population when stimulated by different cell stages from skin fibroblasts (SFs) and umbilical cord mesenchymal cells (UMCs) respectively
Our data confirmed that suppression of peripheral blood mononuclear cells (PBMCs) were present in the group stimulated by the UMC-neural progenitor cells (NPCs) derived from the less immunogenic starting cells UMCs, when compared with the group stimulated by SF-NPCs
Summary
The successful establishment of human embryonic stem cells (hES cells) proved a decisive turning point in biomedical science, providing a renewable source of various cell types for human cell therapy [1]. hES cells derived from early blastocysts are pluripotent and able to differentiate into all cell types present in the body [1,2]. HES cells derived from early blastocysts are pluripotent and able to differentiate into all cell types present in the body [1,2]. Several challenges have been raised in hES-based therapy, such as the ethical issue, low efficacy in establishment, and immune rejection with allogeneic transplantation. These challenges are overcome by the recent breakthrough of induced pluripotent stem cells (iPS cells) reprogrammed from somatic cells with defined factors (Oct, Sox, Klf, and c-Myc) [10]. The autologous cells derived from one’s own iPS cells are theoretically immune tolerant, and have opened new avenues in autologous cell and tissue transplantation [21,22,23].
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