Derivation of Mesenchymal Stem Cells from Induced Pluripotent Stem Cells and Their Application in Genetic Disease Modeling 2307485

Immune cell development from human pluripotent stem cells.

This review summarizes research with a focus on clinical translation of iPSC-derived immune cells, as well as highlights continued challenges and prospects of this field.

Preliminary transcriptome profiling of induced pluripotent stem cell-derived hematopoietic stem and progenitor cells in Kawasaki disease

Background The etiology of Kawasaki disease (KD) remains unclear. Hematopoietic stem and progenitor cells (HSPCs) serve as the precursor cells for a multitude of immune cells. Investigating their initial transcriptional status may help uncover the aberrant immune mechanisms underlying KD. Methods Induced pluripotent stem cells (iPSCs) were reprogrammed from peripheral blood mononuclear cells (PBMCs) isolated from patients with KD and febrile individuals, followed by directed differentiation into HSPCs. We performed bulk RNA-sequencing to compare transcriptomic profiles of iPSC-derived HSPCs between the two groups, with further comparison against integrated HSPC data from public KD single-cell datasets. Results We recruited three patients with KD prior to Intravenous immunoglobulin (IVIG) therapy and three febrile control patients, and successfully established an iPSC-derived HSPCs disease model. Transcriptomic profiling revealed elevated immune and inflammatory response signatures in iPSC-derived HSPCs from patients with KD compared with those from febrile individuals. In addition, in vitro-generated KD iPSC-HSPCs exhibited partial transcriptional features similar to in vivo HSPCs isolated from PBMCs of patients with KD. Gene Set Enrichment Analysis (GSEA) further revealed that gene sets associated with B-cell developmental processes were transcriptionally downregulated in iPSC-derived HSPCs from patients with KD relative to febrile controls. Conclusions iPSC-derived HSPCs from patients with KD display altered immune-inflammatory transcriptional profiles and suppressed B-cell developmental signatures at the transcriptomic level. These preliminary findings suggest that early hematopoietic immune dysregulation may contribute to KD pathogenesis. We propose that these iPSC-derived HSPCs could be a good cellular model for studying the etiology of KD in vitro. These findings are preliminary, constrained by the small sample size and limited to transcriptomic analysis only. Further studies with larger cohorts and functional experiments are needed to verify these results.

Modeling myeloid cell development in health and disease using induced pluripotent stem cells

Key applications of iPSC technology in hemato-oncology are summarized, its major advantages and current limitations are discussed, and emerging directions are highlighted, including scalable iPSC-derived blood cell therapies for inherited and acquired bone marrow failure syndromes and leukemia.

Isolation and Characterization of Mesenchymal Stem Cells from Human Umbilical Cord Tissue.

Comparative Study of Mesenchymal Stem Cell Identity and Chondrogenic Differentiation Capacity of Human Nucleus Pulposus, Adipose and Bone Marrow Tissues Derived Mesenchymal Stem Cells.

BACKGROUND Mesenchymal stem cells (MSCs) are multipotent mesoderm-derived cells with high proliferation capacity, self-renewal, paracrine activity, and multilineage differentiation potential. Autologous MSCs from the same patients are particularly valuable for regenerative therapies, including those targeting degenerative intervertebral disc disorder (DIVDD). METHODS In this study, we directly compared autologous MSC sources obtained from the same patients, thereby reducing biological variability and strengthening translational relevance. We compared MSCs isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and nucleus pulposus (NP-MSCs) obtained from the same DIVDD patient donor (N = 10 donors). We assessed their morphologies, proliferation abilities, immunophenotype, multilineage differentiation capacity, and chondrogenic differentiation-related gene and protein expression. RESULTS All three MSC populations displayed similar fibroblast-like morphology and consistent immunophenotypic profiles. However, their functional properties differed: AD-MSCs exhibited significantly higher proliferative activity and greater adipogenic differentiation potential (p < 0.01 and p < 0.001), while osteogenic and chondrogenic differentiation capacities were comparable across BM-MSCs, AD-MSCs, and NP-MSCs at both gene and protein levels (SOX9 and COMP). CONCLUSION These findings suggest that AD-MSCs offer practical advantages in terms of proliferation capacity and accessibility. However, chondrogenic differentiation capacity was largely comparable across MSC sources. Further mechanistic studies and in vivo validation are required to determine their relative therapeutic efficacy for intervertebral disc regeneration.

Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation

Recognising the central role of VSELs/progenitors and their niche in maintaining tissue homeostasis in vivo could resolve existing roadblocks and guide more effective endogenous regenerative therapies for diseased tissues and age-related dysfunctions.