Year: 2025
Type: article
Abstract: Human invariant natural killer T (iNKT) cells are a conserved population of innate-like T cells that are activated by glycolipid antigens. In addition to their well-known role in anti-tumor function, iNKT cells are also involved in regulating and maintaining hematopoiesis in the bone marrow. Here, we present the reprogramming of human CD4 + Vα24 + Vβ11 + iNKT cells into induced pluripotent stem cells (iNKT-iPSCs) and describe a novel chemically defined, feeder-free 3D spheroid method for generating CD34 + cells from iNKT-iPSCs, followed by their re-differentiation into functional Vα24 + Vβ11 + iNKT cells (i-iNKT) with pro-hematopoietic activity. The i-iNKT cells showed specific binding to CD1d tetramers loaded with the lipid antigen α-galactosylceramide and had a similar transcription factor profile to that of somatic CD4 + iNKT cells. Additionally, in response to CD3 stimulation, the i-iNKT cells produced cytokines with hematopoietic potential and promoted expansion/differentiation of myeloid progenitors. These findings suggest the feasibility of using iPSCs as off-the-shelf i-iNKT cell sources to enhance the hematopoietic activity of bone marrow after hematopoietic stem cell (HSC) transplantation.
Source: Stem Cell Reviews and Reports
Institution: University of Wisconsin–Madison
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
OpenAlex ID: W4417273687