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Reprogramming Peripheral Blood T Cells into Neural Stem Cells

Current methods for the generation of human neurons are not easy to scale to many patients, Creative Bioarray has made progress in developing facile and efficient strategies to reprogram human adult peripheral blood T cells into functional neurons. We have the confidence to provide expert technical support to help our clients study complex human brain disorders.

Introduction

One approach to research the complex genetic backgrounds in human neurons is to reprogram patient cells into iPSCs. However, modeling complex polygenic features using patient-derived iPSCs is challenging due to line-to-line variability and the technical limitations of scaling up to more patients. In addition, iPSCs are usually karyotypically unstable when grown under feeder-free conditions, and their formation is labor-intensive and hard to expand from large numbers of individuals.

The development of cell reprogramming techniques allows direct reprogramming of skin fibroblasts or urinary epithelia into induced neuronal (iN) cells without going through a pluripotent state. However, these donor cells are heterogeneous and variable between individuals, and the process of extensive amplification will inevitably introduce random mutations. In addition, the invasive biopsies required for the derivation of skin fibroblasts add to the complexity of the experiment. It has been recently proposed that human adult peripheral blood mononuclear cells and defined purified T lymphocytes can be directly transformed into fully functional iN cells. Moreover, T cell-derived iN cells exhibited stereotyped neuronal morphologies and expressed a variety of pan-neuronal markers.

Fig 1. Generation of neuronal cells from peripheral blood cells.Fig.1 Generation of neuronal cells from peripheral blood cells. (Tanabe, 2018)

Our Strategies

Researchers at Creative Bioarray have established a specialized and advanced technology platform that allows for a wide range of cell reprogramming services, and we have developed several efficient strategies to help our clients reprogram human adult peripheral blood T-cells into functional neurons.

  • We generated integration-free and non-viral human iPSCs from T cells by electroporation using Epstein-Barr nuclear antigen-1-based epitope vectors and then induced these T-cell-derived iPSCs to differentiate into neuronal cells.
  • We developed a one-step transformation of human peripheral blood T cells directly into neurons using episomal vectors without in vitro expansion. This strategy is more applicable to a larger population of the individual.
  • We improved cell transformation efficiency through small-molecule addition and optimized culture systems.

Applications

  • Generation of clinical-grade iPSCs hereafter
  • Research on neurological disorders (e.g. schizophrenia, autism)
  • Study on complex human brain diseases
  • Development of personalized medical remedies

Advantages

  • Defined, homogeneous and easily accessible donor cell population
  • Methods allow the generation of sufficient neurons
  • Practical and extremely efficient strategies
  • Highly convenient and less invasive

As a company with a long-term focus on developing cell reprogramming technologies and services, Creative Bioarray is well-positioned to provide a wide range of blood cell reprogramming services to clients worldwide. Our professional technical support and reliable after-sales service will accelerate your research. Please contact us for more detailed information.

Reference

  1. Tanabe, K.; et al. Transdifferentiation of human adult peripheral blood T cells into neurons. Proceedings of the National Academy of Sciences. 2018, 115(25): 6470-6475.
For Research Use Only. Not For Clinical Use.