Ectopic expression of CDX4 in human mesenchymal stem cells does not affect HOX gene expression or induce hematopoietic reprogramming.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

In vitro generation of large numbers of autologous hematopoietic stem cells would be extremely useful for clinical applications. Adipose tissue derived mesenchymal stem cells (AT-MSC) are an easily available autologous source for cell therapy applications. Like hematopoietic cells, MSC are of mesodermal origin. The Cdx-Hox pathway is an important genetic program for hematopoiesis, where Cdx4 is a key upstream regulator of the Hox family. We introduced ectopic CDX4 gene in an attempt to reprogram AT-MSC to differentiate along the hematopoietic lineage. To further promote hematopoietic reprogramming, we cultured the transduced cells in cocktails of hematopoietic cytokines, growth factors or epigenetic modifiers. However, despite strong expression of CDX4 at the mRNA and protein levels, neither downstream HOX genes, other genes of importance for hematopoietic development or functional colony forming assays showed any evidence of hematopoietic reprogramming. Thus, despite the close developmental association between these cell types, the introduction of one single master switch transcription factor was not sufficient to promote hematopoietic reprogramming in AT-MSC.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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