Human Umbilical Cord Blood Progenitors: The Potential of These Hematopoietic Cells to Become Neural

Chen, Ning; Hudson, Jennifer E.; Walczak, Piotr; Misiuta, Iwona; Garbuzova‐Davis, Svitlana; Jiang, Lixian; Sanchez‐Ramos, Juan; Sanberg, Paul R.; Zigova, Tanja; Willing, Alison E.

doi:10.1634/stemcells.2004-0284

Cited by 105 publications

(60 citation statements)

References 44 publications

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“…In the long-term culture (60-211 days) cells expressed the early neural marker Nestin (50%) and the early neuronal marker TuJ1 (90%) which were detected immunohistochemically (Fig. 2) and confirmed by Western Blot (see [4]). However the cells expressing TuJ1 do not appear to clearly possess all of the characteristic morphology of neurons mature enough to express this marker such as the fine, long or branched processes (see Figs.…”

Section: Mononuclear Hucb Fraction Initially Consists Mostly Of Hematmentioning

confidence: 80%

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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: Mononuclear Hucb Fraction Initially Consists Mostly Of Hematmentioning

confidence: 80%

“…Our previous experiments showed that, under culture conditions, HUCB cells are able to generate cells with neural characteristics [4]. When transplanted into the neurogenic region of neonatal rat brain, a small fraction of these cells migrate and express neuronal and astroglial proteins [46].…”

Section: Introductionmentioning

confidence: 99%

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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“…Another explanation might be the increased pluripotential capability of the CB stem cell, relative to adult stem cell, with higher proliferative potentials in comparison to BM. [24][25][26] We are aware from animal studies that the addition of mesenchymal stem cells to the SCT product results in less graft rejection, due to the immunomodulating potential of these cells. 27,28 Other advantages of CB include (1) lower rates for acute GvHD and extensive chronic GvHD in comparison to unrelated donors, [29][30][31][32] (2) immediate availability, 23 reducing the period between diagnosis and SCT (in this study 7.5 months), which might improve the long-term outcome, (3) reduced likelihood of transmitting infection (viral) and (4) the suggestion that a more primitive stem cell population might have a greater capacity for transdifferentiation.…”

Section: Discussionmentioning

confidence: 99%

“…27,28 Other advantages of CB include (1) lower rates for acute GvHD and extensive chronic GvHD in comparison to unrelated donors, [29][30][31][32] (2) immediate availability, 23 reducing the period between diagnosis and SCT (in this study 7.5 months), which might improve the long-term outcome, (3) reduced likelihood of transmitting infection (viral) and (4) the suggestion that a more primitive stem cell population might have a greater capacity for transdifferentiation. [24][25][26] This latter capability might be particularly important in SCT for inborn errors of metabolism, by theoretically improving delivery of enzyme to bone, cartilage and brain tissue. More research is warranted to study this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in Europe: a risk factor analysis for graft failure

Boelens

Wynn

O’Meara

et al. 2007

Bone Marrow Transplant

198

186

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Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I, causes progressive deterioration of the central nervous system and death in childhood. Allogeneic stem cell transplantation (SCT) before the age of 2 years halts disease progression. Graft failure limits the success of SCT. We analyzed data on HS patients transplanted in Europe to identify the risk factors for graft failure. We compared outcomes in 146 HS patients transplanted with various conditioning regimens and grafts. Patients were transplanted between 1994 and 2004 and registered to the European Blood and Marrow Transplantation database. Risk factor analysis was performed using logistic regression. 'Survival' and 'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04-0.71; P ¼ 0.02) and reduced-intensity conditioning (OR 0.08; 95% CI 0.02-0.39; P ¼ 0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95% CI 1.20-27.54; P ¼ 0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells or cord blood (CB)); however, significantly more patients who received CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06-82.03; P ¼ 0.044). These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of metabolism' at large. CB increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in SCT for 'inborn errors of metabolism'.

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“…Some of these pluripotent mesodermal cells have recently been shown to differentiate into cells derived from other germ layers both in vitro [4] and in vivo [5]. Therefore, it is not surprising that HUCBmnf cells express numerous markers of either stemness or neural fate in vitro such as nestin, Musashi1, Oct-4, TuJ1, NCAM, A2B5, vimentin, GFAP, S100, GalC and MAP2 [6,7]. Further, these cells express neurotrophic receptors trkB, trkC and p75NTR and cytokine receptor CXCR4 [7,8].…”

Section: Introductionmentioning

confidence: 99%

Trophic factor induction of human umbilical cord blood cellsin vitroandin vivo

et al. 2007

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The mononuclear fraction of human umbilical cord blood (HUCBmnf) is a mixed cell population that multiple research groups have shown contains cells that can express neural proteins. In these studies, we have examined the ability of the HUCBmnf to express neural antigens after in vitro exposure to defined media supplemented with a cocktail of growth and neurotrophic factors. It is our hypothesis that by treating the HUCBmnf with these developmentally-relevant factors, we can expand the population, enhance the expression of neural antigens and increase cell survival upon transplantation. Prior to growth factor treatment in culture, expression of stem cell antigens is greater in the non-adherent HUCBmnf cells compared to the adherent cells (p < 0.05). Furthermore, treatment of the non-adherent cells with growth factors, increases BrdU incorporation, especially after 14 days in vitro (DIV). In HUCBmnf-embryonic mouse striata co-culture, a small number of growth factor treated HUCBmnf cells were able to integrate into the growing neural network and express immature (nestin and TuJ1) and mature (GFAP and MAP2) neural markers. Treated HUCBmnf cells implanted in the subventricular zone predominantly expressed GFAP although some grafted HUCBmnf cells were MAP2 positive. While short-term treatment of HUCBmnf cells with growth and neurotrophic factors enhanced proliferative capacity in vitro and survival of the cells in vivo, the treatment regimen employed was not enough to ensure long-term survival of HUCBmnf-derived neurons necessary for cell replacement therapies for neurodegenerative diseases.

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Human Umbilical Cord Blood Progenitors: The Potential of These Hematopoietic Cells to Become Neural

Cited by 105 publications

References 44 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

Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in Europe: a risk factor analysis for graft failure

Trophic factor induction of human umbilical cord blood cellsin vitroandin vivo

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