MethoCultâ„¢ H4034 Optimum
Methylcellulose-based medium with recombinant cytokines for human cells
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Overview
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This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Educational Materials (19)
Frequently Asked Questions
Publications (40)
A porcine model of Fanconi anemia
PLOS One 2025 Oct
Abstract
Although small animal models of Fanconi anemia (FA) are useful, they do not faithfully replicate many of the clinical features seen in FA patients. We reasoned that a porcine model of FA with its similar physiology and a relatively long lifespan would produce a phenotype more similar to human FA. Targeting FANCA in domestic swine resulted in skeletal abnormalities and extreme sensitivity to interstrand DNA cross-linking agents. In addition, FANCA disruption followed by mitomycin C treatment resulted in a > 10-fold increase in chromosomal radials, a finding that is considered diagnostic for human FA. Bone marrow derived, hematopoietic progenitor cells from a FANCA null pig showed a 75% reduction in colony forming activity compared to wild type. Evaluation of steady state hematopoiesis in the peripheral blood revealed the gradual development of red cell macrocytosis and a reduction in circulating neutrophils. Targeting of FANCD2 failed to produce any biallelic animals demonstrating the loss of FANCD2 function is embryonic lethal in pigs. These results indicate that a porcine model of FANCA holds promise for the development of strategies to prevent the development of bone marrow failure and malignancies in patients with FA.
Continuous map of early hematopoietic stem cell differentiation across human lifetime
Nature Communications 2025 Mar
Abstract
Uncovering early gene network changes of human hematopoietic stem cells (HSCs) leading to differentiation induction is of utmost importance for therapeutic manipulation. We employed single cell proteo-transcriptomic sequencing to FACS-enriched bone marrow hematopoietic stem and progenitor cells (HSPCs) from 15 healthy donors. Pseudotime analysis reveals four major differentiation trajectories, which remain consistent upon aging, with an early branching point into megakaryocyte-erythroid progenitors. However, young donors suggest a more productive differentiation from HSPCs to committed progenitors of all lineages. tradeSeq analysis depicts continuous changes in gene expression of HSPC-related genes (DLK1, ADGRG6), and provides a roadmap of gene expression at the earliest branching points. We identify CD273/PD-L2 to be highly expressed in a subfraction of immature multipotent HSPCs with enhanced quiescence. Functional experiments confirm the immune-modulatory function of CD273/PD-L2 on HSPCs in regulating T-cell activation and cytokine release. Here, we present a molecular map of early HSPC differentiation across human life. Therapeutic application of hematopoietic stem cells requires a thorough understanding of their in situ differentiation pathways. Here they use single cell proteo-transcriptomic sequencing to identify human HSPC differentiation cues and an immunoregulatory function of CD273/PD-L2 on early HSPCs.
Engineering biomimetic bone marrow niche with gene modified mesenchymal stromal cells for ex vivo culture of human hematopoietic stem and progenitor cells
Stem Cell Research & Therapy 2025 Jul
Abstract
BackgroundHematopoietic Stem and Progenitor Cells (HSPCs) gene therapy has shown significant progress, with commercial approval for at least four distinct haematological disorders, and poised for a rapid expansion in the upcoming years. Despite these advancements, the ex vivo culture of HSPCs continues to present significant challenges. The stress induced by ex vivo culture can negatively impact transplantation outcomes, while the need for exogenous cytokine supplementation contributes to the high costs associated with gene therapy products.MethodsWe developed genetically modified human bone marrow MSCs (GM-MSCs) secreting cytokines such as Stem cell factor (SCF), Thrombopoietin (TPO), FMS-like tyrosine kinase-3-ligand (FLT3L), and Interleukin-3 (IL3), closely resembling bone marrow cellular niche to augment HSPCs culture.ResultsHSPCs proliferate on GM-MSCs akin to standard conditions, devoid of external cytokine supplementation and these HSPCs retain their stem cell characteristics, colony-forming potential, stemness gene signatures, and capacity for long-term multilineage reconstitution in NBSGW mice. We demonstrate that our biomimetic feeder layer supports and alleviates stress associated with Homology Directed Repair (HDR) mediated gene-editing of HSPCs for fetal haemoglobin reactivation for a potential application in β-hemoglobinopathies gene therapy.ConclusionOur GM-MSCs offer a compelling alternative to traditional cytokine supplementation by establishing a biomimetic bone marrow niche that fosters HSPC expansion while maintaining their stemness. These findings underscore the potential of engineered MSCs to revolutionize ex vivo HSPCs culture, ultimately enhancing their therapeutic value for gene therapy applications.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04474-4.
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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.
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.
