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Fetal stem cells from extra-embryonic tissues: do not discard.

Marcus AJ, Woodbury D - J. Cell. Mol. Med. (2008)

Bottom Line: Extra-embryonic tissues are large, potentially increasing the number of stem cells that can be extracted.Lastly, the generation and sequestration of cells that form extra-embryonic tissues occurs early in development and may endow resident stem cell populations with enhanced potency.In this review we summarize recent work examining the plasticity and clinical potential of fetal stem cells isolated from extra-embryonic tissues.

View Article: PubMed Central - PubMed

Affiliation: The Ira B. Black Center for Stem Cell Research and the Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA. marcusak@umdnj.edu

ABSTRACT
Stem cells hold promise to treat diseases currently unapproachable, including Parkinson's disease, liver disease and diabetes. Seminal research has demonstrated the ability of embryonic and adult stem cells to differentiate into clinically useful cell types in vitro and in vivo. More recently, the potential of fetal stem cells derived from extra-embryonic tissues has been investigated. Fetal stem cells are particularly appealing for clinical applications. The cells are readily isolated from tissues normally discarded at birth, avoiding ethical concerns that plague the isolation embryonic stem cells. Extra-embryonic tissues are large, potentially increasing the number of stem cells that can be extracted. Lastly, the generation and sequestration of cells that form extra-embryonic tissues occurs early in development and may endow resident stem cell populations with enhanced potency. In this review we summarize recent work examining the plasticity and clinical potential of fetal stem cells isolated from extra-embryonic tissues.

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Amniotic fluid-derived stem cells are multipotent in vitro. RT-PCR analysis of mRNAs for lineages indicated using a retrovirally marked second round subclone of AFS cells. U: Control undifferentiated cells. D: cells maintained under conditions to promote osteogenic (8 days), myogenic (8 days), adipogenic (16 days), endothelial (8 days), hepatic (45 days), neurogenic (8 days) differentiation. Reprinted with permission Nature Biotechnology 25, 100–6 (2007).
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fig02: Amniotic fluid-derived stem cells are multipotent in vitro. RT-PCR analysis of mRNAs for lineages indicated using a retrovirally marked second round subclone of AFS cells. U: Control undifferentiated cells. D: cells maintained under conditions to promote osteogenic (8 days), myogenic (8 days), adipogenic (16 days), endothelial (8 days), hepatic (45 days), neurogenic (8 days) differentiation. Reprinted with permission Nature Biotechnology 25, 100–6 (2007).

Mentions: Subsequent works have further characterized putative stem cell populations isolated from AF. Prusa et al. demonstrated the expression of Oct4 within a subset of AF cells. This is important, as Oct4 expression is associated with pluripotent cells such as embryonic germ cells and ES cells [24]. Demonstration of proliferation within this population further suggests that pluripotent stem cells can be both isolated and propagated from the AF of humans. Other groups have provided evidence that AF-MSCs express both mesodermal and ectodermal gene products [25, 26]. This is consistent with the emerging concept that stem cell populations exist in a multidifferentiated state. In the most comprehensive study to date, De Coppi et al. have examined the potential of amniotic fluid-derived stem cells (AFS cells) isolated from rodents and humans. Employing immunoselection, AF cells expressing the cell surface antigen c-Kit were purified from primary amniocentesis cultures. Isolated cells grew rapidly in culture and were capable of more than 250 population doublings. This demonstrated proliferative capacity far exceeds the Hayflick limit of 50 doublings established for most cultured somatic cells. Importantly, AFS cells display a normal karyotype and maintain telomere length during long-term culture. This latter attribute facilitated the establishment of clonal lines from AFS cells, necessary to establish ‘stemness’of a population. Clonal AFS lines differentiated in vitro to putative adipocytes, endothelial cells, hepatocytes, osteocytes, myocytes and neurons, derivatives of all germ layers (Fig. 2). This broad plasticity appeared to be a general attribute of the selected cells: nineteen different amniocentesis cultures yielded multipotent AFS cell clonal lines [27]. A more recent report has provided evidence of in vitro chondrogenic differentiation of AFS cells, providing further evidence of the plasticity and clinical potential of cells isolated from the AF [28].


Fetal stem cells from extra-embryonic tissues: do not discard.

Marcus AJ, Woodbury D - J. Cell. Mol. Med. (2008)

Amniotic fluid-derived stem cells are multipotent in vitro. RT-PCR analysis of mRNAs for lineages indicated using a retrovirally marked second round subclone of AFS cells. U: Control undifferentiated cells. D: cells maintained under conditions to promote osteogenic (8 days), myogenic (8 days), adipogenic (16 days), endothelial (8 days), hepatic (45 days), neurogenic (8 days) differentiation. Reprinted with permission Nature Biotechnology 25, 100–6 (2007).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4401124&req=5

fig02: Amniotic fluid-derived stem cells are multipotent in vitro. RT-PCR analysis of mRNAs for lineages indicated using a retrovirally marked second round subclone of AFS cells. U: Control undifferentiated cells. D: cells maintained under conditions to promote osteogenic (8 days), myogenic (8 days), adipogenic (16 days), endothelial (8 days), hepatic (45 days), neurogenic (8 days) differentiation. Reprinted with permission Nature Biotechnology 25, 100–6 (2007).
Mentions: Subsequent works have further characterized putative stem cell populations isolated from AF. Prusa et al. demonstrated the expression of Oct4 within a subset of AF cells. This is important, as Oct4 expression is associated with pluripotent cells such as embryonic germ cells and ES cells [24]. Demonstration of proliferation within this population further suggests that pluripotent stem cells can be both isolated and propagated from the AF of humans. Other groups have provided evidence that AF-MSCs express both mesodermal and ectodermal gene products [25, 26]. This is consistent with the emerging concept that stem cell populations exist in a multidifferentiated state. In the most comprehensive study to date, De Coppi et al. have examined the potential of amniotic fluid-derived stem cells (AFS cells) isolated from rodents and humans. Employing immunoselection, AF cells expressing the cell surface antigen c-Kit were purified from primary amniocentesis cultures. Isolated cells grew rapidly in culture and were capable of more than 250 population doublings. This demonstrated proliferative capacity far exceeds the Hayflick limit of 50 doublings established for most cultured somatic cells. Importantly, AFS cells display a normal karyotype and maintain telomere length during long-term culture. This latter attribute facilitated the establishment of clonal lines from AFS cells, necessary to establish ‘stemness’of a population. Clonal AFS lines differentiated in vitro to putative adipocytes, endothelial cells, hepatocytes, osteocytes, myocytes and neurons, derivatives of all germ layers (Fig. 2). This broad plasticity appeared to be a general attribute of the selected cells: nineteen different amniocentesis cultures yielded multipotent AFS cell clonal lines [27]. A more recent report has provided evidence of in vitro chondrogenic differentiation of AFS cells, providing further evidence of the plasticity and clinical potential of cells isolated from the AF [28].

Bottom Line: Extra-embryonic tissues are large, potentially increasing the number of stem cells that can be extracted.Lastly, the generation and sequestration of cells that form extra-embryonic tissues occurs early in development and may endow resident stem cell populations with enhanced potency.In this review we summarize recent work examining the plasticity and clinical potential of fetal stem cells isolated from extra-embryonic tissues.

View Article: PubMed Central - PubMed

Affiliation: The Ira B. Black Center for Stem Cell Research and the Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA. marcusak@umdnj.edu

ABSTRACT
Stem cells hold promise to treat diseases currently unapproachable, including Parkinson's disease, liver disease and diabetes. Seminal research has demonstrated the ability of embryonic and adult stem cells to differentiate into clinically useful cell types in vitro and in vivo. More recently, the potential of fetal stem cells derived from extra-embryonic tissues has been investigated. Fetal stem cells are particularly appealing for clinical applications. The cells are readily isolated from tissues normally discarded at birth, avoiding ethical concerns that plague the isolation embryonic stem cells. Extra-embryonic tissues are large, potentially increasing the number of stem cells that can be extracted. Lastly, the generation and sequestration of cells that form extra-embryonic tissues occurs early in development and may endow resident stem cell populations with enhanced potency. In this review we summarize recent work examining the plasticity and clinical potential of fetal stem cells isolated from extra-embryonic tissues.

Show MeSH
Related in: MedlinePlus