A novel, neural potential of non-hematopoietic human umbilical cord blood stem cells

Domanska-Janik, Krystyna; Bużañska, Leonora; Łukomska, Barbara

doi:10.1387/ijdb.072315kd

Cited by 27 publications

(21 citation statements)

References 106 publications

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“…47 The HUCBNP cell population characterized in this study resembles in certain features the earlier reported unrestricted somatic stem cells isolated from cord blood. 46 The microarray gene expression analysis of HUCBNP indicates that the cells are negative for the hematopoietic markers CD34, CD49c, CD49d, CD62e, CD62p, CD106, CD117, CD133 (as also verified by immunophenotyping), CD235a , HLA-DRB4, HLA-DRB4 and HAS1, and positive for the mesenchymal markers CD13, CD29, CD44, CD49a/b (verified by Western), 6 CD49e, CD73, CD105 and vimentin.…”

Section: Figuresupporting

confidence: 77%

Interferon-γ-induced neuronal differentiation of human umbilical cord blood-derived progenitors

et al. 2009

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Human umbilical cord blood (HUCB) provides a source of progenitors for cell therapy. We isolated and characterized an HUCB-derived population of progenitors (HUCBNP), differentiated toward neuronal phenotype by human neuroblastomaconditioning medium (CM) and nerve growth factor (NGF), which have been found to confer neuroprotection toward hypoxia-mediated neuronal injury. This study investigated whether interferon-c (IFN-c) contributes to HUCBNP differentiation. IFN-c was detected in the CM used for the induction of differentiation of HUCBNP and a neutralizing antibody of IFN-c significantly inhibited either IFN-c or CM-induced differentiation. Transcriptome analysis of CM-differentiated HUCBNP, identified 86 genes as highly upregulated, among them 25 were IFN-induced (such as 2 0 ,5 0 -oligoadenylate synthetase 1 and 2, IFN-induced protein and transmembrane proteins, STAT1 (IFNc-receptor signal transducer and activator of transcription) and chemokine C-X-C motif ligand 5). Treatment of HUCBNP with human recombinant IFN-c, inhibited cell proliferation in a dosedependent manner. IFN-c (1-100 ng/ml) enhanced neuronal differentiation, expressed by neurite outgrowths and increased expression of the neuronal markers b-tubulin III, microtubuleassociated protein 2, neuronal nuclei, neurofilament M and neuronal-specific enolase. IFN-c additively cooperated with NGF to induce the differentiation of HUCBNP. These data indicate that IFN-c promotes neuronal differentiation of HUCBderived progenitors, proposing its use in future protocols towards cell therapy.

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Section: Figuresupporting

confidence: 77%

Interferon-γ-induced neuronal differentiation of human umbilical cord blood-derived progenitors

et al. 2009

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“…S2 C and D). Moreover, CD133 + cells did not spontaneously give rise to neuronal cells when maintained under neural culture conditions for a long period (21,22).…”

Section: Resultsmentioning

confidence: 95%

“…S2 C and D). Moreover, CD133 + cells did not spontaneously give rise to neuronal cells when maintained under neural culture conditions for a long period (21,22).Our initial attempts to convert Sox2-infected CB cells into neurons by using standard neural condition cultures were unsuccessful and infected CD133 + cells underwent apoptosis. Instead, we found that coculture with irradiated human foreskin fibroblasts (i.e., HFF-1 cells) in the presence of bFGF (23) (Fig.…”

mentioning

confidence: 99%

Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc

Giorgetti

Marchetto

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcription factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133 + cells lose their hematopoietic signature and are converted into CB-induced neuronal-like cells (CB-iNCs) by the ectopic expression of the transcription factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immunophenotyping, and electrophysiological analysis show that CBiNCs acquire a distinct neuronal phenotype characterized by the expression of multiple neuronal markers. CB-iNCs show the ability to fire action potentials after in vitro maturation as well as after in vivo transplantation into the mouse hippocampus. This system highlights the potential of CB cells and offers an alternative means to the study of cellular plasticity, possibly in the context of drug screening research and of future cell-replacement therapies.neurons | reprogramming | stem cells T he fate of adult somatic cells is not fixed rigidly and can be reprogrammed by experimental manipulation. The generation of induced pluripotent stem cells (iPSCs) represents the most dramatic evidence that the epigenome of somatic cells are remarkably plastic (1). Recently, it has been reported that fibroblasts can be converted by ectopic expression of defined transcription factors into postmitotic neurons (2-9), neural progenitors (10, 11), and self-renewing neural stem cells (NSCs) (12, 13). However, most reported methods rely on the use of multiple transcription factors and the use of fibroblasts as donor cells.Here we investigate if cord blood (CB) stem cells can be induced to acquire a neuronal phenotype by using only one transcription factor. It has been previously shown that stem cell populations are more amenable to reprogramming than other somatic cells, probably as a result of their preexisting epigenetic state (14,15). Moreover, because of their biological characteristics and availability, CB cells as a donor cell type could offer clear logistic advantages vs. other adult somatic cell types (16,17). These cells can be collected without any risk for the donor and are young cells carrying minimal somatic mutations.Strikingly, we show that forced expression of Sox2 is sufficient to convert CB CD133 + cells into induced neuronal progenitor (NP)-like cells, a conversion process that is augmented by the coexpression of c-Myc. Sox2 is highly expressed in adult NSCs, is one of the earliest functional markers of neuroectodermal specification in the embryo, and plays a key role in the neural lineage specification (18)(19)(20). We show that Sox2-transduced CB cells acquire a distinct neuronal morphology and express multiple neuronal markers in vitro, and that they can be expanded for as many as 25 passages when cultured in permissive condition culture. Moreover, we show that CB-induced neuronal-like cells (CB-iNCs) are able to differentiate in vitro and ...

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“…In vitro by RT-PCR, alizarin red and von Kossa-staining, ALP detection, immunohistochemistry and western blot 8,31,[110][111][112][113] In vitro by safranin-O staining, RT-PCR and immunohistochemistry 8,31 In vitro by immunohistochemistry, RT-PCR, calcium imaging and western blot [114][115][116][117] In vivo in parkinsonian rat model, ischemic rat model [118][119][120][121][122][123] In vitro by immunohistochemistry, RT-PCR, PAS-staining, urea and albumin production, western blot and LDL uptake 31,94,124,125 CD34/AC133-positive (hematopoietic progenitor) cells In vitro by RT-PCR 126 In vivo in NOD/SCID mouse model 95,96 Not defined cells from MNC In vitro by immunohistochemistry, whole-cell patch-clamp, western blot and RT-PCR [127][128][129][130][131] In vivo in spinal cord injury and intra-brain injection in rat and NOD/SCID mouse model 73,76,[80][81][82][83][84][86][87][88][89][90][91][92]<...>…”

Section: Mscmentioning

confidence: 99%