Pancreas developing markers expressed on human mononucleated umbilical cord blood cells

Pessina, Augusto; Eletti, Brighitta; Croera, Cristina; Savalli, Nicoletta; Diodovich, Cristina; Gribaldo, Laura

doi:10.1016/j.bbrc.2004.08.088

Cited by 60 publications

(50 citation statements)

References 32 publications

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“…2 A, i, bottom). The A2 and A4-T cells were further analyzed for expression of specific markers known to be associated with stem and/or progenitor cells including Nestin, a progenitor marker (13), and Oct4 and Nanog, transcriptional determinants essential for the maintenance of an undifferentiated state (14). Nestin and Nanog were distinctly expressed in A2 as well as A4-T monolayers, and were reduced on differentiation into spheroids (Fig.…”

Section: Resultsmentioning

confidence: 99%

Stem and Progenitor-Like Cells Contribute to the Aggressive Behavior of Human Epithelial Ovarian Cancer

Bapat

Mali²,

Koppikar³

et al. 2005

Cancer Research

699

612

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The cellular mechanisms underlying the increasing aggressiveness associated with ovarian cancer progression are poorly understood. Coupled with a lack of identification of specific markers that could aid early diagnoses, the disease becomes a major cause of cancer-related mortality in women. Here we present direct evidence that the aggressiveness of human ovarian cancer may be a result of transformation and dysfunction of stem cells in the ovary. A single tumorigenic clone was isolated among a mixed population of cells derived from the ascites of a patient with advanced ovarian cancer. During the course of the study, yet another clone underwent spontaneous transformation in culture, providing a model of disease progression. Both the transformed clones possess stem cell-like characteristics and differentiate to grow in an anchorage-independent manner in vitro as spheroids, although further maturation and tissue-specific differentiation was arrested. Significantly, tumors established from these clones in animal models are similar to those in the human disease in their histopathology and cell architecture. Furthermore, the tumorigenic clones, even on serial transplantation continue to establish tumors, thereby confirming their identity as tumor stem cells. These findings suggest that: (a) stem cell transformation can be the underlying cause of ovarian cancer and (b) continuing stochastic events of stem and progenitor cell transformation define the increasing aggression that is characteristically associated with the disease. (Cancer Res 2005; 65(8): 3025-9)

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Section: Resultsmentioning

confidence: 99%

Stem and Progenitor-Like Cells Contribute to the Aggressive Behavior of Human Epithelial Ovarian Cancer

Bapat

Mali²,

Koppikar³

et al. 2005

Cancer Research

699

612

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show abstract

“…Stem cell plasticity has been investigated in various organs, using rodent bone marrow cells [31]. A recent report demonstrated that human CB MNCs expressed pancreas-related genes such as nestin, neurogenin-3 (Ngn3), and paired box gene 4 (Pax4) at the RNA level [32]. The primary purpose of the present study was to determine whether "human" hematopoietic tissue-derived cells possessed the capacity to regenerate the insulin-producing cells.…”

Section: Discussionmentioning

confidence: 99%

Human Cord Blood–Derived Cells Generate Insulin‐Producing Cells In Vivo

et al. 2005

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Here we report the capacity of human cord blood (CB) -derived cells to generate insulin-producing cells. To investigate in vivo capacity of human CB-derived cells, T celldepleted mononuclear cells were intravenously transplanted into nonobese diabetic/severe combined immunodeficient/β 2 -microglobulin null mice within 48 hours of birth. At 1-2 months post-transplantation, immunofluorescence staining for insulin and fluorescence in situ hybridization (FISH) analysis using a human chromosome probe indicated that human CB-derived cells generated insulin-producing cells at a frequency of 0.65% ± 0.64% in xenogeneic hosts. Reverse transcription-polymerase chain reaction analysis confirmed the transcription of human insulin in the pancreatic tissue of the recipient mice. To clarify the mechanism underlying CBderived insulin-producing cells, double FISH analysis using species-specific probes was performed. Almost equal proportions of human chromosome + murine chromosome − insulin + cells and human chromosome + murine chromosome + insulin + cells were present in recipient pancreatic islets. Taken together, human CB contains progenitor cells, which can generate insulin-producing cells in recipient pancreatic tissues across a xenogeneic histocompatibility barrier by fusiondependent and -independent mechanisms. Stem Cells

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“…Similar to bone marrow derived stem cells, the utility of these cord stem cells in diabetic mice is still not completely understood. Markers for pancreatic progenitors can been identified on human umbilical cord blood cells [89]. In vitro cultures of human umbilical cord blood has also yielded islet-like structures capable of insulin and C-peptide production [90], however the in vivo behavior of these cells remains unknown.…”

Section: Umbilical Cord Blood-derived Stem Cellsmentioning

confidence: 99%

Cellular Therapies for Type 1 Diabetes

Lee¹,

Grossman²,

Chong³

2008

Horm Metab Res

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Type 1 diabetes mellitus (T1DM) is a disease that results from the selective autoimmune destruction of insulin-producing β-cells. This disease process lends itself to cellular therapy because of the single cell nature of insulin production. Murine models have provided opportunities for the study of cellular therapies for the treatment of diabetes, including the investigation of islet transplantation, and also the possibility of stem cell therapies and islet regeneration. Studies in islet transplantation have included both allo-and xeno-transplantation and have allowed for the study of new approaches for the reversal of autoimmunity and achieving immune tolerance. Stem cells from hematopoietic sources such as bone marrow and fetal cord blood, as well as from the pancreas, intestine, liver and spleen promises either new sources of islets or may function as stimulators of islet regeneration. This review will summarize the various cellular interventions investigated as potential treatments of T1DM.

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Pancreas developing markers expressed on human mononucleated umbilical cord blood cells

Cited by 60 publications

References 32 publications

Stem and Progenitor-Like Cells Contribute to the Aggressive Behavior of Human Epithelial Ovarian Cancer

Stem and Progenitor-Like Cells Contribute to the Aggressive Behavior of Human Epithelial Ovarian Cancer

Human Cord Blood–Derived Cells Generate Insulin‐Producing Cells In Vivo

Cellular Therapies for Type 1 Diabetes

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