²Ñ±ð²õ±ð²Ô°ä³Ü±ô³Ùâ„¢-ACF Chondrogenic Differentiation Kit
Animal component-free medium for the differentiation of MSCs into chondrocytes
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- L-Glutamine
Cell culture supplement
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Resources and Publications
Educational Materials (9)
Publications (16)
Increased BMP/SMAD Signaling by PD-MSCs Promotes Bone Formation in an Ovariectomized Mouse Model of Osteoporosis
International Journal of Molecular Sciences 2025 Oct
Abstract
Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for degenerative diseases due to their ability to modulate disease progression through paracrine mechanisms. Among various MSC sources, placenta-derived MSCs (PD-MSCs) offer significant advantages, including high proliferation capacity, reduced senescence, and low immunogenicity, making them ideal for allogeneic applications. In this study, we investigated the therapeutic effects of PD-MSC transplantation in an estrogen-deficiency-induced osteoporosis mouse model. Mice were divided into three groups: a normal control group, a non-transplanted osteoporosis group, and a PD-MSC-transplanted group. Our findings demonstrated that PD-MSC transplantation significantly improved osteoporosis-related parameters, including increased femur weight, bone volume, bone mineral density, and calcium deposition. Additionally, estrogen levels were elevated, bone formation markers were upregulated, and bone resorption markers were downregulated. PD-MSCs also reduced inflammatory cytokine levels while enhancing anti-inflammatory factors. Notably, the BMP/SMAD signaling pathway, crucial for bone formation, was significantly upregulated. These results suggest that PD-MSC transplantation effectively restores bone homeostasis by inhibiting osteoclast activity, promoting osteogenesis, and modulating inflammation. This study provides strong evidence supporting the potential of PD-MSCs as a novel therapeutic strategy for osteoporosis, offering a regenerative and anti-inflammatory approach to bone disease management.
Continuous collection of human mesenchymal-stromal-cell-derived extracellular vesicles from a stirred tank reactor operated under xenogeneic-free conditions for therapeutic applications
Stem Cell Research & Therapy 2025 Apr
Abstract
BackgroundMesenchymal-stromal-cell-derived extracellular vesicles (MSC-EVs) play a key role in the paracrine effects of MSC and have demonstrated therapeutic potential in various preclinical models. However, clinical translation is hindered by manufacturing practices relying on planar culture systems, fetal bovine serum (FBS)-supplemented media, and non-scalable, low-purity EV isolation methods that fail to meet dose and safety requirements, underscoring the need for innovative approaches. In this study, we developed a scalable platform to manufacture human MSC-EVs at clinically relevant numbers, integrating continuous collection of EV-enriched conditioned media (CM) using a stirred-tank reactor (STR) under xenogeneic-free conditions and a scalable downstream process.MethodsWharton’s jelly-derived MSC (MSC(WJ)) were expanded using microcarriers in a controlled STR using human platelet lysate (hPL)-supplemented medium. Then, a 3-day EV production stage, featuring continuous harvesting of the CM, was established using a novel serum-/xeno(geneic)-free exosome depleted-hPL supplement. For the isolation of MSC-EVs, a scalable process was implemented by pairing tangential flow filtration and anion exchange chromatography. Isolated MSC-EVs were characterised using nanoparticle tracking analysis, protein and zeta potential quantification, western blot analysis of EV protein markers, transmission electron microscopy and uptake studies of fluorescently labelled-EVs.ResultsThe system sustained the efficient expansion of MSC(WJ), reaching a total of (6.03 ± 0.181) x 107 cells after 7 days, which corresponds to a 30.1 ± 0.740-fold expansion. Upon a 3-day continuous CM harvesting, a total of (2.13 ± 0.301) x 1012 EVs were isolated corresponding to a particle yield factor of (1.26 ± 0.186) x 104 EVs/cell/day. MSC-EVs presented high purity levels ((5.53 ± 1.55) x 109 particles/µg), a homogeneous small size distribution (mean diameter of 115 ± 4.88 nm), a surface charge of -23.4 ± 6.23 mV, positive detection of tetraspanins CD9 and CD63 and syntenin-1 and displayed a typical cup-shaped morphology. MSC-EVs were readily incorporated by endothelial cells and two human breast cancer cell lines.ConclusionsOverall, the scalable and Good Manufacturing Practices (GMP)-compliant platform established herein enabled the reproducible manufacturing of MSC-EVs with high purity and generally accepted characteristics concerning size, protein markers, surface charge, morphology, and cellular internalization, validating its potential for future clinical applications.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04341-2.
Ultralow-dose irradiation enables engraftment and intravital tracking of disease initiating niches in clonal hematopoiesis
Scientific Reports 2024 Sep
Abstract
Recent advances in imaging suggested that spatial organization of hematopoietic cells in their bone marrow microenvironment (niche) regulates cell expansion, governing progression, and leukemic transformation of hematological clonal disorders. However, our ability to interrogate the niche in pre-malignant conditions has been limited, as standard murine models of these diseases rely largely on transplantation of the mutant clones into conditioned mice where the marrow microenvironment is compromised. Here, we leveraged live-animal microscopy and ultralow dose whole body or focal irradiation to capture single cells and early expansion of benign/pre-malignant clones in the functionally preserved microenvironment. 0.5 Gy whole body irradiation (WBI) allowed steady engraftment of cells beyond 30 weeks compared to non-conditioned controls. In-vivo tracking and functional analyses of the microenvironment showed no change in vessel integrity, cell viability, and HSC-supportive functions of the stromal cells, suggesting minimal inflammation after the radiation insult. The approach enabled in vivo imaging of Tet2 + /− and its healthy counterpart, showing preferential localization within a shared microenvironment while forming discrete micro-niches. Notably, stationary association with the niche only occurred in a subset of cells and would not be identified without live imaging. This strategy may be broadly applied to study clonal disorders in a spatial context.
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PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT º£½ÇÆƽâ°æ, REFER TO WWW.º£½ÇÆƽâ°æ.COM/COMPLIANCE.
