Abstract
The intrinsic capacity of human hematopoietic stem cells (hHSCs) to reconstitute myeloid and lymphoid lineages combined with their self-renewal capacity hold enormous promises for gene therapy as a viable treatment option for a number of immune-mediated diseases, most prominently for inborn errors of immunity (IEI). The current development of such therapies relies on disease models, both in vitro and in vivo, which allow the study of human pathophysiology in great detail. Here, we discuss the current challenges with regards to developmental origin, heterogeneity and the subsequent implications for disease modeling. We review models based on induced pluripotent stem cell technology and those relaying on use of adult hHSCs. We critically review the advantages and limitations of current models for IEI both in vitro and in vivo. We conclude that existing and future stem cell-based models are necessary tools for developing next generation therapies for IEI.
Highlights
Inborn errors of immunity (IEI, or primary immunodeficiencies [PIDs]) encompass a group of more than 400 inherited disorders that result in partial or complete loss of normal immune development or function [1]
The term “adult stem cells” used throughout this review refers to stem cells found after birth, in opposition to embryonic stem cells (ESC), which are referring to stem cells found during development
It is important to note that ESC are pluripotent, having the capacity to develop into all three germ layers and cell types, while adult stem cells are specific to a certain organ or restricted cell types
Summary
Inborn errors of immunity (IEI, or primary immunodeficiencies [PIDs]) encompass a group of more than 400 inherited disorders that result in partial or complete loss of normal immune development or function [1]. The transplantation of hHSCs is currently used for the care of hematologic malignancies such as leukemia, certain cellular immunodeficiencies and autoimmune diseases [3]. The rationale behind this approach is an initial broad lymphoablation of the defective immune cells eradiating the recipient’s immunological memory and subsequent infusion of functional hHSCs from. Cells 2022, 11, 108 as leukemia, certain cellular immunodeficiencies and autoimmune diseases [3] The rationale behind this approach is an initial broad lymphoablation of the defective imm uofn2e2 cells eradiating the recipient’s immunological memory and subsequent infusion of functional hHSCs from donors, thereby allowing an extensive immunological renewal.
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