Brain from bone: Efficient “meta-differentiation” of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent

Kohyama, Jun; Abe, Hitoshi; Shimazaki, Takuya; Koizumi, Amane; Nakashima, Kinichi; Gojo, Satoshi; Taga, Tetsuya; Hata, Jun Ichi; Umezawa, Akihiro

doi:10.1046/j.1432-0436.2001.680411.x

Cited by 273 publications

(216 citation statements)

References 42 publications

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“…This process may be useful as a preliminary step in the purification of CD34 ϩ cells by magnetic cell selection (e.g., Isolex™ magnetic cell selection or CliniMACS™) because reduction of mononuclear cells is essential for obtaining high purity and yield of these cells by magnetic cell selection. 13,14 Hematopoietic stem cells as well as several other stem and progenitor cells are found in bone marrow 26,27 and umbilical cord blood. 28,29 Most current research on the use of stem cells in tissue engineering has focused on the development of tissue and organs from specific stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…28,29 Most current research on the use of stem cells in tissue engineering has focused on the development of tissue and organs from specific stem cells. 27,29 Safe and simple separation and purification of specific stem or mesenchymal stem cells from bone marrow or umbilical cord blood are essential for this application. Membrane separation can provide a more sanitary and simple isolation of these cells than FACS or other separation methods.…”

Section: Discussionmentioning

confidence: 99%

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Peripheral blood cell separation through surface‐modified polyurethane membranes

Higuchi

Yamamiya

Yoon

et al. 2003

J Biomedical Materials Res

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Cell separation from peripheral blood was investigated using surface-modified polyurethane (PU) membranes with different functional groups. Both red blood cells and platelets could pass through unmodified PU and PU-SO 3 H membranes, whereas the red blood cells preferentially passed through PU-N(C 2 H 5 ) 2 and PU-NHC 2 H 4 OH membranes. The permeation ratio of T and B cells was Ͻ25% for the surface-modified and unmodified PU membranes. CD34 ϩ cells have been recognized as various kinds of stem cells including hematopoietic and mesenchymal stem cells. The adhesiveness of CD34 ϩ cells on the PU membranes was found to be higher than that of red blood cells, platelets, T cells, or B cells. Overall, the adhesiveness of blood cells on the PU membranes increased in the following order: red blood cells Յ platelets Ͻ T cells Յ B cells Ͻ CD34 ϩ cells. Treatment of PU-COOH membranes with a human albumin solution to detach adhered blood cells, allowed recovery of mainly CD34 ϩ cells in the permeate, whereas both red blood cells and platelets could be isolated in the permeate using unmodified PU membranes. The PU membranes showed different permeation and recovery ratios of specific cells depending on the functional groups attached to the membranes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Peripheral blood cell separation through surface‐modified polyurethane membranes

Higuchi

Yamamiya

Yoon

et al. 2003

J Biomedical Materials Res

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“…The results of triplicate experiments showed that 5.0 and 5.4% of the UCBMSC and UCB-TERT-21 cells became positive for fat droplets with Oil-Red stain as a result of adipogenic induction and Ͼ90% of the cells were positive on ALP staining after osteogenic induction. We also induced these cells to differentiate into multiple lineages by the methods for neural (Kohyama et al, 2001), cardiomyogenic (Makino et al, 1999;Takeda et al, 2004), and chondrogenic (Imabayashi et al, 2003) lineages; however, the UCBMSC and UCBTERT-21 cells were not induced to differentiate into these lineages in vitro.…”

Section: Osteogenic and Adipogenic Differentiation Potentials Of Ucbmmentioning

confidence: 99%

Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16^INK4a/RB Braking Pathway

Terai

Uyama

Sugiki

et al. 2005

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Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to serve as an excellent alternative to bone marrow-derived human mesenchymal stem cells. However, it is difficult to study them because of their limited life span. To overcome this problem, we attempted to produce a strain of UCBMSCs with a long life span and to investigate whether the strain could maintain phenotypes in vitro. UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span. The UCBMSCs underwent 30 population doublings (PDs) and stopped dividing at PD 37. The UCBMSCs newly established with hTERT (UCBTERTs) proliferated for >120 PDs. The p16 INK4a /RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16 INK4a /RB pathway. The characteristics of the UCBTERTs remained unchanged during the prolongation of life span. UCBTERTs provide a powerful model for further study of cellular senescence and for future application to cell-based therapy by using umbilical cord blood cells. INTRODUCTIONHuman mesenchymal stem cells (hMSCs) can be a useful source of cells for transplantation for several reasons: they have the ability to proliferate and differentiate into mesodermal tissues, and they entail no ethical or immunological problems (Caplan, 1991;Prockop, 1997;Caplan and Bruder, 2001). hMSCs have been studied extensively over the past 3 decades, and numerous independent research groups have successfully isolated hMSCs from a variety of sources, most commonly, from the bone marrow (Owen, 1988;Umezawa et al., 1992;Jaiswal et al., 1997;Makino et al., 1999;Pittenger et al., 1999;Sekiya et al., 2004). Umbilical cord blood (UCB) contains circulating stem/progenitor cells, and the cells contained in UCB are known to be distinct from those contained in bone marrow and adult peripheral blood (Mayani and Lansdorp, 1998). Isolation, characterization, and differentiation of clonally expanded hMSCs derived from UCB (UCBMSCs) have been reported (Goodwin et al., 2001;Lee et al., 2004), and UCBMSCs have been found to have multipotency, and the immunophenotype of the clonally expanded cells is consistent with that reported for bone marrow mesenchymal stem cells. Even now, most UCB is regarded as medical waste in the delivery rooms. Aspirating bone marrow from patients is, however, an invasive procedure, and the proliferation and differentiation capacity of hMSCs decreases with the donor age (D'Ippolito et al., 1999). Therefore, the applications of UCB should be further expanded.UCBMSCs will be useful sources for cell transplantation, however, it is difficult to study and apply them because of their limited life span. One of the reasons for this is that normal human cells undergo a limited number of cell division in culture and then enter a nondividing state called "senescence" (Hayflick, 1976;Campisi...

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“…Differentiation of MSCs into neural elements in vitro (Woodbury et al, 2000;Sanchez-Ramos et al, 2000;Deng et al, 2001;Kohyama et al, 2001) and in vivo (Kopen et al, 1999;Zhao et al, 2002) has raised fundamental questions about stem cell lineage, commitment, and plasticity.…”

mentioning

confidence: 99%

Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis

Woodbury

Reynolds

Black

2002

J of Neuroscience Research

427

302

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Bone marrow stromal stem cells (MSCs) normally differentiate into mesenchymal derivatives but recently have also been converted into neurons, classical ectodermal cells. To begin defining underlying mechanisms, we extended our characterization of MSCs and the differentiated neurons. In addition to expected mesodermal mRNAs, populations and clonal lines of MSCs expressed germinal, endodermal, and ectodermal genes. Thus, the MSCs are apparently "multidifferentiated" in addition to being multipotent. Conversely, the differentiating neurons derived from populations and clonal lines of MSCs expressed the specific markers ␤-III tubulin, tau, neurofilament-M, TOAD-64, and synaptophysin de novo. The transmitter enzymes tyrosine hydroxylase and choline acetyltransferase were localized to neuronal subpopulations. Our observations suggest that MSCs are already multidifferentiated and that neural differentiation comprises quantitative modulation of gene expression rather than simple on-off switching of neural-specific genes.

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Brain from bone: Efficient “meta-differentiation” of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent

Cited by 273 publications

References 42 publications

Peripheral blood cell separation through surface‐modified polyurethane membranes

Peripheral blood cell separation through surface‐modified polyurethane membranes

Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16^INK4a/RB Braking Pathway

Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis

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Brain from bone: Efficient “meta-differentiation” of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent

Cited by 273 publications

References 42 publications

Peripheral blood cell separation through surface‐modified polyurethane membranes

Peripheral blood cell separation through surface‐modified polyurethane membranes

Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking Pathway

Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis

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Product

Resources

About

Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16^INK4a/RB Braking Pathway