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Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) have greater potential for generating chondrocytes without hypertrophic and fibrotic phenotypes compared to bone marrow-derived mesenchymal stem/stromal cells (BMSCs). However, there is a lack of research demonstrating the use of autologous iMSCs for repairing articular chondral lesions in large animal models. In this study, we aimed to evaluate the effectiveness of autologous miniature pig (minipig) iMSC-chondrocyte (iMSC-Ch)-laden implants in comparison to autologous BMSC-chondrocyte (BMSC-Ch)-laden implants for cartilage repair in porcine femoral condyles. iMSCs and BMSCs were seeded into fibrin glue/nanofiber constructs and cultured with chondrogenic induction media for 7 days before implantation. To assess the regenerative capacity of the cells, 19 skeletally mature Yucatan minipigs were randomly divided into microfracture control, acellular scaffold, iMSC, and BMSC subgroups. A cylindrical defect measuring 7 mm in diameter and 0.6 mm in depth was created on the articular cartilage surface without violating the subchondral bone. The defects were then left untreated or treated with acellular or cellular implants. Both cellular implant-treated groups exhibited enhanced joint repair compared to the microfracture and acellular control groups. Immunofluorescence analysis yielded significant findings, showing that cartilage treated with iMSC-Ch implants exhibited higher expression of COL2A1 and minimal to no expression of COL1A1 and COL10A1, in contrast to the BMSC-Ch-treated group. This indicates that the iMSC-Ch implants generated more hyaline cartilage-like tissue compared to the BMSC-Ch implants. Our findings contribute to filling the knowledge gap regarding the use of autologous iPSC derivatives for cartilage repair in a translational animal model. Moreover, these results highlight their potential as a safe and effective therapeutic strategy. The online version contains supplementary material available at 10.1186/s13287-025-04215-7.

Here we systematically investigated genomic alterations from the initiation of induced pluripotent stem (iPS) cell generation to induced mesenchymal stromal/stem cell differentiation. We observed a total of ten copy number alterations (CNAs) and five single-nucleotide variations (SNVs) during the phases of reprogramming, differentiation and passaging. We identified a higher frequency of CNAs and SNVs in iPS cells generated using the Sendai virus (SV) method compared with those generated with episomal vectors (Epi). Specifically, all SV-iPS cell lines exhibited CNAs during the reprogramming phase, while only 40% of Epi-iPS cells showed such alterations. Additionally, SNVs were observed exclusively in SV-derived cells during passaging and differentiation, with no SNVs detected in Epi-derived lines. Gene expression analysis revealed upregulation of chromosomal instability-related genes in late-passage SV-iPSCs, further indicating increased genomic instability. Notably, TP53 mutations were identified, underscoring the vulnerability of the gene and the critical need for careful genomic scrutiny when preparing iPS cells and derived cell lines. Genomic instability in induced pluripotent stem cells revealedThis study explores the potential of using induced pluripotent stem (iPS) cells to create mesenchymal stem (MS) cells for medical treatments. iPS cells can be reprogrammed from regular cells and can become any cell type, including MS cells, which are important for tissue repair. However, a concern is that iPS cells might develop genetic changes that could affect their safety. Here researchers investigated these genetic changes during the creation and growth of iPS cells and their transformation into MS cells using advanced techniques such as chromosomal microarray and next-generation sequencing, alongside conventional methods. The study found that iPS cells often develop genetic alterations, which can persist as they are turned into MS cells. The results suggest that while iPS cells hold promise for regenerative medicine, careful monitoring of genetic stability is crucial. Future research should focus on improving methods to ensure safety of iPS cell-derived therapies.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Human-induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) represent a promising and renewable cell source for therapeutic applications. A systematic evaluation of the immunological properties and engraftment potential of iMSCs generated from urine-derived iPSCs is lacking, which has impeded their broader application. In this study, we differentiated urine-derived iPSCs into iMSCs and assessed their fundamental MSC characteristics, immunogenicity, immunomodulatory capacity and in vivo engraftment. Compared to umbilical cord-derived MSCs (UCMSCs), iMSCs demonstrated an enhanced proliferative capacity, a higher level of regenerative gene expression, and lower immunogenicity, strengthening resistance to apoptosis induced by allogeneic peripheral blood mononuclear cells (PBMCs) and the NK-92 cell line. In addition, iMSCs exhibited a diminished ability to inhibit T cell proliferation and activation compared with UCMSCs. Transcriptomic analyses further revealed the decreased expression of immune regulatory factors in iMSCs. After transfusion into mouse models, iMSCs engrafted in the lungs, liver, and spleen and exhibited the ability to migrate to tumor tissues. Our results indicated that iMSCs generated from urine-derived iPSCs have a significant replicative capacity, low immunogenicity and unique immunomodulatory properties, and hence offer obvious advantages in immune privilege and allogenic therapeutic application prospects.