Derivation of Induced Pluripotent Stem Cells from Human Peripheral Blood T Lymphocytes

Abstract

Induced pluripotent stem cells (iPSCs) hold enormous potential for the development of personalized in vitro disease models, genomic health analyses, and autologous cell therapy. Here we describe the generation of T lymphocyte-derived iPSCs from small, clinically advantageous volumes of non-mobilized peripheral blood. These T-cell derived iPSCs (“TiPS”) retain a normal karyotype and genetic identity to the donor. They share common characteristics with human embryonic stem cells (hESCs) with respect to morphology, pluripotency-associated marker expression and capacity to generate neurons, cardiomyocytes, and hematopoietic progenitor cells. Additionally, they retain their characteristic T-cell receptor (TCR) gene rearrangements, a property which could be exploited for iPSC clone tracking and T-cell development studies. Reprogramming T-cells procured in a minimally invasive manner can be used to characterize and expand donor specific iPSCs, and control their differentiation into specific lineages.

Rejuvenating T cells

“…Several groups have generated T cell-derived iPS cells, [5][6][7][8] but not much is known about differentiating these cells back into antigen-specific T cells.…”

Differentiation of Human Atrial Myocytes From Endothelial Progenitor Cell-Derived Induced Pluripotent Stem Cells

“…Several studies have successfully reprogramed blood cells such as T cells and B cells to iPSCs but genetic reprogramming is limited by a low capacity of these cells to expand in culture, modest reprogramming efficiency and the presence of DNA rearrangements in their receptor loci by generation of antigen specific surface immunoglobulins [150][151][152]. In addition, one study paradoxically demonstrated that B cell derived iPSCs failed to differentiate into B cells [151].…”

Promise and challenges of human iPSC-based hematologic disease modeling and treatment

“…Blood sample collection and storage are among the routine procedures in hospitals and clinics. Therefore, significant efforts have been made to develop efficient and safe procedures for reprogramming various types of blood cells (Table 1) [10,11,[13][14][15][16][17][18][19][20][21]. Umbilical cord blood (UCB) cell banks provide another rich source for cells with diverse HLA types.…”

“…T cells, which are abundant in peripheral blood and amenable to ex vivo expansion after stimulation of T cell receptor (TCR) activation, were the first subtypes of lineage-committed human blood cells being reprogrammed [16][17][18]. Analyses of the TCR genomic loci had shown the evidence of V(D)J recombination in resultant iPSCs, demonstrating their T cell origin [16][17][18]24]. These studies also provided the most convincing evidence that terminally differentiated human cells can be reprogrammed into a pluripotent state.…”