Trophic factor induction of human umbilical cord blood cells<i>in vitro</i>and<i>in vivo</i>

Chen, Ning; Kamath, Siddharth G.; Newcomb, Jennifer D.; Hudson, Jennifer E.; Garbuzova‐Davis, Svitlana; Bickford, Paula C.; Davis-Sanberg, Cyndy; Sanberg, Paul R.; Zigova, Tanja; Willing, Alison E.

doi:10.1088/1741-2560/4/2/013

Cited by 23 publications

(22 citation statements)

References 80 publications

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“…Unfortunately, the morphology of these cells does not fully support their suggested neuronal phenotype. A recent study from our lab has shown that the floating cells possess greater proliferation capacity and more neural characteristics than the adherent fraction of cells [5]. Such a distinction was not made in any major capacity in this study and may contribute to this.…”

Section: Discussioncontrasting

confidence: 50%

“…Our study would appear to support this, since the absence of an immunogenic background in the NOD/SCID mice did not aid survival. Chen et al [5] also demonstrated enhanced proliferation and survival following growth factor treatment.…”

Section: Discussionmentioning

confidence: 96%

“…Repetition of this study using short-term cultures would help to determine if this is a limiting factor in these mice. A short-term study in which the HUCB cells were treated with a number of growth and neurotrophic factors demonstrated enhanced survival, though this was not found to result in long-term survival [5]. Interestingly, both Bouhan et al [2] and Kelly et al [25] have demonstrated that culture of embryonic neural precursors with either a chemically defined or EGF and FGF-2 containing media, results in growth of neurons.…”

Section: Discussionmentioning

confidence: 99%

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Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

Walczak¹,

Chen²,

Eve³

et al. 2007

Brain Research Bulletin

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The use of stem cells and other cells as therapies is still in its infancy. One major setback is the limited survival of the grafts, possibly due to immune rejection. Studies were therefore performed with human umbilical cord blood cells (HUCB) to determine the ability of these cells to survive in vivo and the effect of the immune response on their survival by transplantation into the normal striatum of immunodeficient NOD SCID mice.Long-term culture of HUCB cells resulted in several different populations of cells, including one that possessed fine processes and cell bodies that resembled neurons. Their neuronal phenotype was confirmed by immunohistochemical staining for the early neuronal marker TuJ1 and the potentially neural marker Nestin. Five days after cell transplantation of this neuronal phenotype, immunohistochemical staining for human mitochondria confirmed the presence of living HUCB cells in the mouse striatum, with cells localized at the site of injection, expressing early neural and neuronal markers (Nestin and TuJ1) as well as exhibiting neuronal morphology. However, no evidence of surviving cells was apparent 1 month postgrafting. The absence of signs of T cell-mediated rejection, such as CD4 and CD8 lymphocytes and minimal changes in microglia and astrocytes, suggest that cell loss was not due to a T cell-mediated immune response. In conclusion HUCB cells can survive long-term in vitro and undergo neuron-like differentiation. In mice, these cells do not survive a month. This may relate to the differentiated state of the cells transplanted into the unlesioned striatum, rather than T cell-mediated immunological rejection.

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Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

Walczak¹,

Chen²,

Eve³

et al. 2007

Brain Research Bulletin

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“…As one potential source of neural stem cells, CBMNCs contain various progenitor cells including a large population of CD34 + hematopoietic stem cells, a small population of mesenchymal stem cells, and very few endothelial progenitor cells and muscle satellite cells. These progenitor cells are highly proliferative with the potential to differentiate towards a neural cell fate, and secrete various growth and neurotrophic factors (Fan et al, 2005;Habich et al, 2006;Chen et al, 2005Chen et al, , 2007Lee et al, 2007;Bachstetter et al, 2008). These factors, when secreted into the immediate extracellular environment, play important roles in paracrine signaling to regulate hematopoietic processes, immune responses, angiogenesis, and cell proliferation, differentiation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of umbilical cord blood mononuclear cells increases levels of nerve growth factor in the cerebrospinal fluid of patients with autism

Q¹,

Cf²,

Dy³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We aimed to evaluate the levels of growth factors in the cerebrospinal fluid (CSF) of patients with autism after transplantation of umbilical cord blood mononuclear cells (CBMNCs). Fourteen subjects diagnosed with autism received transplantation of CBMNCs first through intravenous infusion, and three times subsequently through intrathecal injections. A 2-mL sample of CSF was taken before each intrathecal injection. CSF levels of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were determined by enzyme-linked immunosorbent assay. All data are reported as means ± SD and were analyzed using the SPSS 10.0 software. Oneway analysis of variance with post-hoc F-and Q-tests were performed for comparisons. NGF levels in the CSF were significantly increased after transplantation (213.54 ± 56.38 after the third versus 28.32 ± 12.22 ng/L after the first transplantation; P < 0.05), while VEGF and bFGF levels did (2015) not change significantly. Therefore, transplantation of CBMNCs could increase NGF levels in the CSF of patients with autism.

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“…The capability of mononuclear hUCB cells to express neural antigens has recently been determined following in vitro exposure to media supplemented with a cocktail of growth and neurotrophic factors. When the floating mononuclear fraction of hUCB cells was exposed to a neurogenic circumstance by treatment with growth factors and neurotrophins, this fraction of cell increased their proliferation and expression of neural antigens, and they also survived longer in vivo [67].…”

Section: Transdifferentiation Into Neural Lineagesmentioning

confidence: 99%

Transplantation of Umbilical Cord Blood Stem Cells for Treating Spinal Cord Injury

Park

Lee

Borlongan

et al. 2010

Stem Cell Rev and Rep

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Spinal cord injury (SCI) develops primary and secondary damage to neural tissue and this often results in permanent disability of the motor and sensory functions. However, there is currently no effective treatment except methylprednisolone, and the use of methylprednisolone has also been questioned due to its moderate efficacy and the drug's downside. Regenerative medicine has remarkably developed since the discovery of stem cells, and many studies have suggested the potential of cell-based therapies for neural injury. Especially, the therapeutic potential of human umbilical cord blood cells (hUCB cells) for intractable neurological disorders has been demonstrated using in vitro and vivo models. The hUCB cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Their ability to produce several neurotropic factors and to modulate immune and inflammatory reactions has also been noted. Recent evidence has emerged suggesting alternative pathways of graft-mediated neural repair that involve neurotrophic effects. These effects are caused by the release of various growth factors that promote cell survival, angiogenesis and anti-inflammation, and this is all aside from a cell replacement mechanism. In this review, we present the recent findings on the stemness properties and the therapeutic potential of hUCB as a safe, feasible and effective cellular source for transplantation in SCI. These multifaceted protective and restorative effects from hUCB grafts may be interdependent and they act in harmony to promote therapeutic benefits for SCI. Nevertheless, clinical studies with hUCB are still rare because of the concerns about safety and efficiency. Among these concerns, the major histocompatibility in allogeneic transplantation is an important issue to be addressed in future clinical trials for treating SCI.

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Trophic factor induction of human umbilical cord blood cellsin vitroandin vivo

Cited by 23 publications

References 80 publications

Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

Transplantation of umbilical cord blood mononuclear cells increases levels of nerve growth factor in the cerebrospinal fluid of patients with autism

Transplantation of Umbilical Cord Blood Stem Cells for Treating Spinal Cord Injury

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