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

Abstract

The breakthrough development of induced pluripotent stem cells (iPSCs) raises the prospect of patient-specific treatment for many diseases through the replacement of affected cells. However, whether iPSC-derived functional cell lineages generate a deleterious immune response upon auto-transplantation remains unclear. In this study, we differentiated five human iPSC lines from skin fibroblasts and urine cells into neural progenitor cells (NPCs) and analyzed their immunogenicity. Through co-culture with autogenous peripheral blood mononuclear cells (PBMCs), we showed that both somatic cells and iPSC-derived NPCs do not stimulate significant autogenous PBMC proliferation. However, a significant immune reaction was detected when these cells were co-cultured with allogenous PBMCs. Furthermore, no significant expression of perforin or granzyme B was detected following stimulation of autogenous immune effector cells (CD3

Global Proteomic and Methylome Analysis in Human Induced Pluripotent Stem Cells Reveals Overexpression of a Human TLR3 Affecting Proper Innate Immune Response Signaling

“…The data demonstrate that the cell reprogramming process alters specific aspects of the innate immune response resulting in a possible suppression of immunogenicity, supporting similar findings recently described for human iPSC‐derived cells . We discover two distinct states in human iPSC‐derived cells related to overexpression WT TLR3 and Isoform TLR3 that could impinge on future clinical applications and disease modeling: Unstimulated state: increased IL6 associated with increased WT TLR3 expression in F2 cells (iPSC‐derived cells) (Fig.…”

“…Interestingly, a recent study found that differentiation of human iPSC results in a loss of immunogenicity and leads to the induction of tolerance, despite expected antigen expression differences between iPSC‐derived versus original somatic cells . In further agreement with this study, it has also been demonstrated that neural progenitor cells from human iPSC generated less autogenous immune response, possibly by altered toll like receptor pathway signaling they did not assess . This observation among others brings forward the interesting possibility that human iPSC‐derived cells may benefit from a suppressed immunogenic microenvironment favoring initial survival and subsequent engraftment and tissue regeneration.…”

Effect of mild hypothermia preconditioning against low temperature (4°C) induced rat liver cell injury in vitro

“…For the Immunofluorescence staining, the primary antibodies used were anti-rat voltage dependent anion channel (VDAC; 1:100, Santa), anti-rat hexokinase 2 (HK2, 1:50, Santa). After 12 hours of incubation at 4°C, the samples were washed 3 times with PBS and processed using second antibodies and DAPI, then observed using Axio Scope A1 as the reference [24, 25]. …”

Generation of Human Induced Pluripotent Stem Cell-Derived Bona Fide Neural Stem Cells for Ex Vivo Gene Therapy of Metachromatic Leukodystrophy

“…In the search for alternative cell sources, human induced pluripotent stem cells (hiPSCs) represent a superior candidate when considering their extensive self‐renewal ability and wide developmental potential . The availability of patient‐specific hiPSC‐derived NSCs (hiPS‐NSCs) may overcome immunological issues as well as ethical concerns. In addition, combining iPSC technology with novel gene transfer/gene editing strategies has great potential for developing autologous cell‐based treatments for genetic diseases, including rare metabolic diseases with severe CNS involvement .…”