The HOX Code as a “biological fingerprint” to distinguish functionally distinct stem cell populations derived from cord blood

AbstractMesenchymal stem cells (MSC) have been isolated from almost every adult tissue. In cord blood (CB), different non-hematopoietic CD45-, CD34− adherent cell populations can be generated: the cord blood derived MSC (CB-MSC), that behave almost like MSC from bone marrow (BM-MSC), and unrestricted somatic stem cells (USSC) which show a distinct differentiation potential into all three germ layers. However, distinguishing these populations easily by molecular markers is still a concern. In this study we were able to present the HOX expression pattern of USSC, CB-MSC and BM-MSC, which in fact allows a discrimination of these populations.Briefly, RT-PCR analysis of the HOX code revealed a high similarity between BM-MSC and CB-MSC, which are both HOX-positive, whereas USSC resembled H9 embryonic stem cells HOX-negative.Especially HOXA9, HOXB7, HOXC10 and HOXD8 are good candidate markers to discriminate MSC from USSC. Thus, our data suggest that the "biological fingerprint" based on the HOX code can be used to distinguish functionally distinct MSC populations derived from bone marrow and cord blood

Induction of pluripotency in human cord blood unrestricted somatic stem cells

Objective: Generation of induced pluripotent stem (iPS) cells from human cord blood (CB)-derived unrestricted somatic stem cells and evaluation of their molecular signature and differentiation potential in comparison to human embryonic stem cells. Materials and Methods: Unrestricted somatic stem cells isolated from human CB were reprogrammed to iPS cells using retroviral expression of the transcription factors OCT4, SOX2, KLF4, and C-MYC. The reprogrammed cells were analyzed morphologically, by quantitative reverse transcription polymerase chain reaction, genome-wide microRNA and methylation profiling, and gene expression microarrays, as well as in their pluripotency potential by in vivo teratoma formation in severe combined immunodeficient mice and in vitro differentiation. Results: CB iPS cells are very similar to human embryonic stem cells morphologically, at their molecular signature, and in their differentiation potential. Conclusions: Human CB-derived unrestricted somatic stem cells offer an attractive source of cells for generation of iPS cells. Our findings open novel perspectives to generate human leukocyte antigen-matched pluripotent stem cell banks based on existing CB banks. Besides the obvious relevance of a second-generation CB iPS cell bank for pharmacological and toxicological testing, its application for autologous or allogenic regenerative cell transplantation appears feasible.close201