Stem Cell-Based Disease Models for Inborn Errors of Immunity

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.

Current status and development direction of immunomodulatory therapy for intervertebral disk degeneration

“…Mesenchymal stem cells (MSCs) are multifunctional and self-renewing cells in tissues such as bone marrow and adipose tissue ( 104 , 105 ). In recent years, MSCs from different sources have been widely used to treat IVDD.…”

“…MSCs sensitize inflammatory factors and exert anti-inflammatory effects by switching macrophages from the M1 (proinflammatory) to the M2 (anti-inflammatory) phenotype through immunomodulators (e.g., prostaglandin E2) ( 107 ). On the other hand, MSCs can inhibit the proliferation and activation of T and B cells of any kind and tissue origin, which greatly attenuates the associated adaptive immune response ( 104 ). Furthermore, evidence suggests that bone marrow mesenchymal stem cells (BMSCs) can differentiate into NP-like cells and are resistant to catabolism ( 108 ).…”