Stem Cell Therapy in Drug Discovery & Development

Stem cells are unspecialized cells of the human body that can differentiate into specific cells and have the ability to self-renewal. They originate from embryos and adult cells or develop from other cells using reprogramming techniques. Owning to their ability to build every tissue in the human body, stem cells were used to promote the repair response of diseased, dysfunctional, or injured regions. Stem cell therapy is the next chapter of regenerative medicine, which has been used in pilot studies as a potential cell-based therapy for various diseases. The type of stem cell that scientists commonly use are mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs).

Drug development strategies using human iPSCs Fig.1 Drug development strategies using human iPSCs (Avior, 2016)

Mesenchymal Stem Cells (MSCs)

Mesenchymal stem cells are multipotent adult stem cells that the connective tissue or stroma that surrounds the body’s organs and other tissues. MSCs have the ability of self-renewal and differentiation, which can turn into multiple tissues including cartilage, bone, and connective tissue. To date, MSCs have been used to treat a variety of conditions and they are important for making and repairing skeletal tissues. It has been reported that MSCs can a variety of chemokines and cytokines to restore the normal tissue metabolism and counteract inflammation.

Embryonic Stem Cells (ESCs)

Embryonic stem cells (ESCs) are pluripotent, self-renewing cells that are derived from the inner mass cells of a human embryo. They can differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. As an important tool, ESCs hold enormous promise for understanding normal development and disease. They have been used in the treatment of devastating disorders, such as neurological disease, spinal cord injury, and blindness. However, the use of human embryos to derive these cells ignited a diverse ethical issue.

Induced Pluripotent Stem Cells (iPSCs)

The widely used artificial stem cell is induced pluripotent stem cells (iPSCs), which are produced from somatic cells through co-expression of defined pluripotency-associated factors. In 2006, Takahashi and Yamanaka discovered that the introduction of a set of transcription factors (Oct4, Sox2, Klf4, and c-Myc) could convert somatic cells into pluripotent stem cells. The iPSCs can propagate indefinitely and differentiate into all three embryonic germ layers. Compared with other stem cells, the iPSCs can be created from the tissue of the same patient to avoid immune rejection. In addition, the use of iPSCs technology eliminates the ethical implications.

Pluripotent Stem Cells in Disease Modeling & Drug Discovery

The human disease models play an important role in understanding the disease mechanisms and therapies’ development. The emergence of pluripotent stem cells creates new possibilities for the establishment of models and their use in drug screening. Currently, either ESCs or patient-specific iPSCs have been used to generate the disease model, which has become increasingly favored for purposes of drug discovery. The patient-derived induced pluripotent stem cell models have primary disease properties and can be a novel platform for drug screening.

Reference

  1. Avior, Y., Sagi, I. and Benvenisty, N., 2016. Pluripotent stem cells in disease modeling and drug discovery. Nature Reviews Molecular Cell Biology, 17(3), pp.170-182.
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