scholarly journals Establishment of Humanized Mice from Peripheral Blood Mononuclear Cells or Cord Blood CD34+ Hematopoietic Stem Cells for Immune‐Oncology Studies Evaluating New Therapeutic Agents

2020 ◽  
Vol 89 (1) ◽  
Author(s):  
Bhavna Verma ◽  
Amy Wesa
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angela Duong ◽  
Alesya Evstratova ◽  
Adam Sivitilli ◽  
J. Javier Hernandez ◽  
Jessica Gosio ◽  
...  

AbstractMitochondrial health plays a crucial role in human brain development and diseases. However, the evaluation of mitochondrial health in the brain is not incorporated into clinical practice due to ethical and logistical concerns. As a result, the development of targeted mitochondrial therapeutics remains a significant challenge due to the lack of appropriate patient-derived brain tissues. To address these unmet needs, we developed cerebral organoids (COs) from induced pluripotent stem cells (iPSCs) derived from human peripheral blood mononuclear cells (PBMCs) and monitored mitochondrial health from the primary, reprogrammed and differentiated stages. Our results show preserved mitochondrial genetics, function and treatment responses across PBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach will serve as a model for more widespread evaluation of mitochondrial health relevant to a wide range of human diseases using readily accessible patient peripheral (PBMCs) and stem-cell derived brain tissue samples.


2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093085
Author(s):  
Xiaoyu Li ◽  
Bowen Zhang ◽  
Hong Wang ◽  
Xiaolu Zhao ◽  
Zijie Zhang ◽  
...  

Objectives The effect of age on the response of peripheral blood mononuclear cells (PBMCs) to immunosuppression induced by human periodontal ligament stem cells (hPDLSCs) is unclear. The identity of the cytokines most effective in inducing the PBMC immune response remains unknown. This study investigated the effects of age on immunophenotype, proliferation, activation, and cytokine secretion capacities of PBMCs following co-culture with hPDLSCs. Methods PBMCs were collected from younger (16–19 years) and older (45–55 years) donors, then co-cultured with confirmed hPDLSCs for various lengths of time. T lymphocyte proliferation and cell surface marker expression were analyzed by flow cytometry. Cytokine expression levels were measured by quantitative polymerase chain reaction assays and enzyme-linked immunosorbent assays. Results CD28 expression by T lymphocytes decreased with age, indicating reduced proliferation; CD95 expression increased with age, indicating enhanced apoptosis. Moreover, hPDLSCs inhibited T lymphocyte proliferation in both age groups; this inhibition was stronger in cells from older donors than in cells from younger donors. Age reduced the secretion of interleukin-2 and interferon-γ, whereas it increased the secretion of tumor necrosis factor-β by PBMCs cultured with hPDLSCs. Conclusions Aging may have a robust effect on the response of PBMCs towards hPDLSC-induced immunosuppression.


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