scholarly journals Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells

2017 ◽  
Vol 21 (1) ◽  
pp. 144-148 ◽  
Author(s):  
Prajna Guha ◽  
John W. Morgan ◽  
Gustavo Mostoslavsky ◽  
Neil P. Rodrigues ◽  
Ashleigh S. Boyd
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Differentiated Cells ◽  
Induced Pluripotent

scholarly journals Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells

2013 ◽  
Vol 12 (4) ◽  
pp. 407-412 ◽  
Author(s):  
Prajna Guha ◽  
John W. Morgan ◽  
Gustavo Mostoslavsky ◽  
Neil P. Rodrigues ◽  
Ashleigh S. Boyd
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Differentiated Cells ◽  
Induced Pluripotent

scholarly journals Deprivation of human natural killer cells and antitumor immune response

2014 ◽  
Vol 2 ◽  
Author(s):  
Vyacheslav Ogay ◽  
Aliya Sekenova ◽  
Inpyo Choi
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Nk Cells ◽  
Induced Pluripotent Stem Cells ◽  
Natural Killer ◽  
Pluripotent Stem Cells ◽  
Antitumor Immune Response ◽  
Efficient Treatment ◽  
Cd34 Cells ◽  
Induced Pluripotent

Introduction: Cell-based immunotherapy has been given increased attention as a treatment for cancer. Human natural killer (NK) cells are resident lymphocyte populations. They exhibit potent antitumor activity without human leukocyte antigen matching and without prior antigen exposure. They also are a promising tool for immunotherapy of solid and hematologic cancers. However, most cancer patients do not have enough NK cells to induce an effective antitumor immune response. This demonstrates a need for a source of NK cells that can supplement the endogenous cell population.Material and methods: In this study, we derived induced pluripotent stem cells (iPSCs) from peripheral blood T-lymphocytes using Sendai virus vectors.Results: Generated iPSCs exhibited monoclonal T cell receptors (TCR) rearrangement in their genome, a hallmark of mature terminally differentiated T cells. These iPSCs were differentiated into NK cells using a two-stage coculture system: iPSCs into hematopoietic CD34+ cells with feeder cells M210-B4 (ATCC, USA) and CD34+ cells into mature NK cells with AFT024 cells (ATCC, USA). Our results showed that iPSC-derived NK cells expressed CD56, CD16, NKp 44 and NKp 46, possessed high cytotoxic activity  and produced high level of interferon-γ.Conclusion: Based on our data, derivation of NK cells from induced pluripotent stem cells should be considered in the treatment of oncologic diseases.This would allow for the development of cell therapy for cancer using immunologically compatible NK cells derived from iPSCs. This may contribute to a more efficient treatment of oncologic diseases in addition to traditional cancer treatment.

scholarly journals Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Tackla S. Winston ◽  
Kantaphon Suddhapas ◽  
Chenyan Wang ◽  
Rafael Ramos ◽  
Pranav Soman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Culture Conditions ◽  
Serum Free ◽  
Differentiated Cells ◽  
Induced Pluripotent

Combination of stem cell technology and 3D biofabrication approaches provides physiological similarity to in vivo tissues and the capability of repairing and regenerating damaged human tissues. Mesenchymal stem cells (MSCs) have been widely used for regenerative medicine applications because of their immunosuppressive properties and multipotent potentials. To obtain large amount of high-quality MSCs without patient donation and invasive procedures, we differentiated MSCs from human-induced pluripotent stem cells (hiPSC-MSCs) using serum-free E6 media supplemented with only one growth factor (bFGF) and two small molecules (SB431542 and CHIR99021). The differentiated cells showed a high expression of common MSC-specific surface markers (CD90, CD73, CD105, CD106, CD146, and CD166) and a high potency for osteogenic and chondrogenic differentiation. With these cells, we have been able to manufacture MSC tissue rings with high consistency and robustness in pluronic-coated reusable PDMS devices. The MSC tissue rings were characterized based on inner diameter and outer ring diameter and observed cell-type-dependent tissue contraction induced by cell-matrix interaction. Our approach of simplified hiPSC-MSC differentiation, modular fabrication procedure, and serum-free culture conditions has a great potential for scalable manufacturing of MSC tissue rings for different regenerative medicine applications.

Differentiation of human induced pluripotent stem cells into testosterone-producing Leydig-like cells

Endocrinology ◽  
2021 ◽  
Author(s):  
Takaki Ishida ◽  
Michiyo Koyanagi-Aoi ◽  
Daisuke Yamamiya ◽  
Atsushi Onishi ◽  
Katsuya Sato ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Leydig Cells ◽  
Late Onset ◽  
Testosterone Replacement Therapy ◽  
Promising Alternative ◽  
Differentiated Cells ◽  
Induced Pluripotent ◽  
Late Onset Hypogonadism

Abstract Late-onset hypogonadism (LOH) syndrome due to a partial lack of testosterone, which is mainly secreted by Leydig cells in the testes, decreases the quality of life of older men. Leydig cell transplantation is expected to be a promising alternative to conventional testosterone replacement therapy (TRT) for LOH syndrome. We herein report a simple and robust protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into Leydig-like cells by doxycycline-inducible overexpression of NR5A1 and treatment with a combination of 8-bromoadenosine-3’,5’-cyclic monophosphate (8-Br-cAMP) and forskolin. The differentiated cells expressed the steroidogenic enzyme genes STAR, CYP11A1, CYP17A1 and HSD3B2 and the specific markers of adult Leydig cells HSD17B3, INSL3 and LHCGR. Furthermore, we confirmed the secretion of functional testosterone from the cells into the culture supernatant by a testosterone-sensitive cell proliferation assay. These findings showed that the hiPSCs were able to be differentiated into Leydig-like cells, supporting the expectation that hiPSC-derived Leydig-like cells can be novel tools for treating LOH syndrome.

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

Stem Cells ◽  
2019 ◽  
Vol 37 (4) ◽  
pp. 476-488 ◽  
Author(s):  
Jordi Requena ◽  
Ana Belen Alvarez-Palomo ◽  
Montserrat Codina-Pascual ◽  
Raul Delgado-Morales ◽  
Sebastian Moran ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Induced Pluripotent Stem Cells ◽  
Innate Immune Response ◽  
Pluripotent Stem Cells ◽  
Innate Immune ◽  
Methylome Analysis ◽  
Induced Pluripotent

scholarly journals Cell type determination for cardiac differentiation occurs soon after seeding of human induced pluripotent stem cells

2021 ◽  
Author(s):  
Connie L Jiang ◽  
Yogesh Goyal ◽  
Naveen Jain ◽  
Qiaohong Wang ◽  
Rachel E Truitt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Cardiac Differentiation ◽  
Marker Genes ◽  
Directed Differentiation ◽  
Cell Type ◽  
Differentiated Cells ◽  
Induced Pluripotent

Cardiac directed differentiation of human induced pluripotent stem cells consistently produces a mixed population of cardiomyocytes and non-cardiac cell types even when using very well-characterized protocols. We wondered whether differentiated cell types might result from intrinsic differences in hiPS cells prior to the onset of differentiation. By associating individual differentiated cells that share a common hiPS cell precursor, we were able to test whether expression variability in differentiated cells was pre-determined from the hiPS cell state. Although within a single experiment, differentiated cells that share an hiPS cell progenitor were more transcriptionally similar to each other than to other cells in the differentiated population, when the same hiPS cells were differentiated in parallel, we did not observe high transcriptional similarity across differentiations. Additionally, we found that substantial cell death occurred during differentiation in a manner that suggested that all cells were equally likely to survive or die, suggesting that there was no intrinsic selection bias for cells descended from particular hiPS cell progenitors. These results led us to wonder about how cells grow out spatially during the directed differentiation process. Labeling cells by their expression of a few canonical cell type marker genes, we showed that cells expressing the same marker tended to occur in patches observable by visual inspection, suggesting that cell type determination across multiple cell types, once initiated, is maintained in a cell-autonomous manner for multiple divisions. Altogether, our results show that while there is substantial heterogeneity in the initial hiPS cell population, that heterogeneity is not responsible for heterogeneous outcomes, and that the window during which cell type specification occurs is likely to begin shortly after the seeding of hiPS cells for differentiation.

scholarly journals Response to Stimulations Inducing Circadian Rhythm in Human Induced Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 620
Author(s):  
Hitomi Kaneko ◽  
Taku Kaitsuka ◽  
Kazuhito Tomizawa
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Clock Genes ◽  
Directed Differentiation ◽  
Differentiated Cells ◽  
Temperature Rhythm ◽  
Low Levels ◽  
Induced Pluripotent

Regenerative medicine and disease modeling are expanding rapidly, through the development of human-induced pluripotent stem cells (hiPSCs). Many exogeneous supplements are often used for the directed differentiation of hiPSCs to specific lineages, such as chemicals and hormones. Some of these are known to synchronize the circadian clock, like forskolin (Frk) and dexamethasone (Dex); however, the response to these stimulations has not been fully elucidated for hiPSCs. In this study, we examined the response of clock genes to synchronizing stimulation, and compared it with fully differentiated cells, U2OS, and fibroblasts. The expression of clock genes did not show circadian rhythms in hiPSCs with Frk and Dex, which could be due to the significantly low levels of BMAL1. On the other hand, a circadian-like rhythm of D-box binding protein (DBP) expression was observed in hiPSCs by culturing them in an environment with a simulated body temperature. However, the inhibition of temperature-inducible factors, which are involved in temperature rhythm-induced synchronization, could not repress the expression of such rhythms, while the inhibition of HIF-1α significantly repressed them. In summary, we suggest that clock genes do not respond to the synchronizing agents in hiPSCs; instead, a unique circadian-like rhythm is induced by the temperature rhythm.

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