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Review
. 2020 Jul;22(suppl 1):1-10.
doi: 10.22074/cellj.2020.6849. Epub 2020 Jul 18.

Induced Pluripotent Stem Cell Meets Severe Combined Immunodeficiency

Reza Kouchaki  1 , Bahareh Abd-Nikfarjam  2 , Amir Hosein Maali  3 , Saeid Abroun  4 , Farshad Foroughi  2 , Sasan Ghaffari  5 , Mehdi Azad  6
Affiliations
Review

Induced Pluripotent Stem Cell Meets Severe Combined Immunodeficiency

Reza Kouchaki et al. Cell J. 2020 Jul.

Abstract

Severe combined immunodeficiency (SCID) is classified as a primary immunodeficiency, which is characterized by impaired T-lymphocytes differentiation. IL2RG, IL7Ralpha, JAK3, ADA, RAG1/RAG2, and DCLE1C (Artemis) are the most defective genes in SCID. The most recent SCID therapies are based on gene therapy (GT) of hematopoietic stem cells (HSC), which are faced with many challenges. The new studies in the field of stem cells have made great progress in overcoming the challenges ahead. In 2006, Yamanaka et al. achieved "reprogramming" technology by introducing four transcription factors known as Yamanaka factors, which generate induced pluripotent stem cells (iPSC) from somatic cells. It is possible to apply iPSC-derived HSC for transplantation in patients with abnormality or loss of function in specific cells or damaged tissue, such as T-cells and NK-cells in the context of SCID. The iPSC-based HSC transplantation in SCID and other hereditary disorders needs gene correction before transplantation. Furthermore, iPSC technology has been introduced as a promising tool in cellular-molecular disease modeling and drug discovery. In this article, we review iPSC-based GT and modeling for SCID disease and novel approaches of iPSC application in SCID.

Keywords: Hematopoietic Stem Cell Transplantation; Induced Pluripotent Stem Cell; Primary Immunodeficiency; Severe Combined Immunodeficiency.

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Conflict of interest statement

There is no conflict of interest in this study.

Figures

Fig.1
Fig.1
A depiction of the most common types of SCID. The deficiencies appear in different stages of T-cell development. AK2-deficiency, ADA-SCID, and PNP-SCID are caused by a deficiency in the developmental stages of the bone marrow. The defective signals from the pre-TCR and TCR (CD45, CD3ξ, CD3ε, CD3δ), ILR γ and α, RAG1/2, JAK3, ZAP70, MHCII, and ARTEMIS deficiencies occur in thymus developmental stages. SCID; Severe combined immunodeficiency, ADA; Adenosine-deaminase, PNP; Purine nucleo-side phosphorylase, and TCR; T-cell receptor.
Fig.2
Fig.2
A review of iPSC technology applications in SCID. OKSM RFs reprogram somatic cells to iPSCs. Hematopoietic RFs are used to induce hematopoiesis in iPSCs. The prepared cells are used for in vitro modeling and HSCT (after GT). SCID; severe combined immunodeficiency, OKSM; OCT4, KLF4, SOX2 and c-MYC, RFs; Reprogramming factors, iPSCs; Induced pluripotent stem cell, HSCT; Hematopoietic stem cell transplantation, and GT; Gene therapy.
See this image and copyright information in PMC

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