Stem Cells - Placental Cord Blood

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Introduction

Human Blastocyst (Carnegie Stage 3)

The term "stem cell" is used so freely these days in many different forums that it is difficult sometimes understand without context what scientists, politicians, ethicists and commentators are discussing. In terms of human development, the embryonic stem cell with totipotential occurs at the blastocyst stage, mainly in the first and second week of development. After this period the inner cell mass, which forms the entire embryo, will differentiate into embryonic germ layers with restricted differentiation potential.

Stem cells as well as having the capacity to differentiate into any (totipotential) or multiple (pluripotential) cell types, have the unique capacity of self-renewal.

In vitro fertilization and growth of the blastocyst, allows isolation of these cells and their subsequent use in stem cell research. It is the collection, production and possible therapeutic applications of these stem cells which has recently attracted worldwide attention.

Mice cloned from adult keratinocytes

A key step in the development of stem cell research has been the identification of cell surface markers (proteins) which identify these cells and their state of undifferentiation.

A useful guide (online PDF document) to stem cells was produced in a report by the National Institute of Health (NIH, USA, May 2000) Stem Cells: A Primer (note large size - 4.84 Mb) and more recently NIH has established a Stem Cell information page.

Stem Cell Links: Introduction | Timeline | Placental Cord Blood | Adult | Induced pluripotent stem cell | Yamanaka Factors | Somatic Cell Nuclear Transfer | Ethics | Organoids | Adult Human Cell Types | Category:Stem Cell

Some Recent Findings

  • Pluripotent stem cell-derived gametes[1] "An emerging body of data suggests that pluripotent stem cells may be able to differentiate to form eggs and sperm. We discuss the state of the science and the potential social implications and offer recommendations for addressing some of the ethical and policy issues that would be raised by the availability of stem cell-derived gametes. ...PSC-derived gamete research represents the convergence of several areas of ethical and policy debate and inquiry‚Äîstem cell research, human genetic research, reproductive technologies, and human enhancement‚Äîbringing many of today's most contentious ethical issues into the same conversation."
  • Generation of pluripotent stem cells from adult human testis[2]"Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis."
  • Tlx3 neuronal differentiation from embryonic stem cells[3] "The T cell leukemia 3 (Tlx3) gene has been implicated in specification of glutamatergic sensory neurons in the spinal cord. ...The sequential and coordinated expression of the proneural and neuronal subtype-specific genes identifies Tlx3 as a selector gene in ES cells undergoing neural differentiation."
  • USA Food and Drug Administration (FDA) 2008 public hearing on the safety of therapies that use human embryonic stem cells. "Cellular Therapies Derived from Human Embryonic Stem Cells "Considerations for Pre-Clinical Safety Testing and Patient Monitoring, April 10, 2008" The biotech company Geron plans to trial a stem cell based therapy for patients with acute spinal-cord injury. (More?FDA Meeting Briefing Document PDF)

Stem Cell Use

Results from a recent Australian survey into couples' views on the use of supernumerary embryos:[4]

  • 40% (123/311) returned completed questionnaires.
  • 42% most common decision was donation to research (altruistic motives and desire not to waste embryos were determinants of embryo donation).

Determinants of disposal were not wanting a full sibling to existing children and opposition of embryo research.

  • 45% found deciding distressing.
  • 69% approved of embryo donation to stem-cell research.

Cord Blood Stem Cell

Placental cord blood is a rich souce of haematopoietic stem cells for transplantation. Cord blood can collected at birth, with no impact on the mother or neonate, and stured in cord blood banks for later use. (More? Stem Cells - Cord Blood)

BBC (UK) A brief article on Cord Blood stem cells and their therapeutic potential.

Spermatogonial Stem Cell (SSC)

In the male testes are a population of spermatogonia cells that differentiate and meiotically divide to form spermatozoa cells (male germ cells).

  • Production of knockout mice by random or targeted mutagenesis in spermatogonial stem cells.[5]
  • Spermatogonial stem cells: questions, models and perspectives.[6]
  • [Spermatogonial stem cells: characteristics and experimental possibilities.[7]
  • Genetic and epigenetic properties of mouse male germline stem cells during long-term culture.[8]
  • Expansion of murine spermatogonial stem cells through serial transplantation.[9]

Adult Stem Cell

Adult stem cells, with pluropotentiality, are found in three main body systems: intestinal epithelium, epidermis, and bone marrow. (More? Adult Stem Cells)

Inducible Stem Cells

Inducible pluripotent stem cells (iPS) require a minimum of key defined transcription factors (Oct3/4, Sox2, Klf4, c-Myc, Nanog and Lin28) are required to be introduced into a cell to "induce" that cell to revert to a stem cell phenotype.

  • Induction of pluripotent stem cells from adult human fibroblasts by defined factors.[10]
  • Generation of induced pluripotent stem cells by reprogramming mouse embryonic fibroblasts with a four transcription factor, doxycycline inducible lentiviral transduction system.[11]

Stem Cell Markers

In order to carry out research on stem cells, it is important to be able to identify them. A number of different research groups in the late 90's generated several antibodies which specifically identified undifferentiated, differentiating or differentiated stem cells from a number of different sources and species. Note that the nomenclature in some cases is based upon the antibody used to identify the cell surface marker.

  • Stage-Specific Embryonic Antigen-1 (SSEA-1) cell surface embryonic antigen which has a role in cell adhesion, migration and differentiation and is often differentially expressed during development. Can be identified by Davor Solter (monoclonal antibody MC-480) (SSEA-1).
  • Stage-Specific Embryonic Antigen-4 (SSEA-4) cell surface embryonic antigen of human teratocarcinoma stem cells (EC), human embryonic germ cells (EG) and human embryonic stem cells (ES) which is down-regulated following differentiation of human EC cells. Antigen not expressed on undifferentiated murine EC, ES and EG cells but upregulated on differentiation of murine EC and ES cells. Can be identified by Davor Solter (monoclonal antibody MC-813-70) (SSEA-4)
  • Tumor Rejection Antigen (TRA-1-60) Sialylated Keratan Sulfate Proteoglycan expressed on the surface of human teratocarcinoma stem cells (EC), human embryonic germ cells (EG) and human embryonic stem cells (ES).
  • Tumor Rejection Antigen (TRA-1-81) antigen expressed on the surface of human teratocarcinoma stem cells (EC), human embryonic germ cells (EG) and human embryonic stem cells (ES). Both TRA antibodies identify a major polypeptide (Mr 240 kDa) and a minor polypeptide (Mr 415 kDa).
  • Oct-4 (Pou5f1 ‚Äì Mouse Genome Informatics) gene has an essential role in control of developmental pluripotency (Oct4 knockout embryo blastocysts die at the time of implantation). Oct4 also has a role in maintaining viability of mammalian germline.
  • Stem Cell Antigen 1 (Sca-1) member of the Ly-6 family of GPI-linked surface proteins (Mr 18 kDa) and a major phenotypic marker for mouse hematopoietic progenitor/stem cell subset.
  • CD133, AC133, prominin 5 transmembrane glycoprotein (865 aa) expressed on stem cells with hematopoietic and nonhematopoietic differentiation potential.
  • Alpha 6 integrin

References

Data based on information from Appendix E.II. NIH Report "Stem Cells: Scientific Progress and Future Research Directions", Chemicon International- Stem cell marker antibodies OMIM and other sources.

Stem Cell Fake Result

Hwang Woo-suk (Korean pioneer of stem cell research) Resigns A Seoul National University investigation of the original data in Science paper Jun (2005;308: 1777-83) "Eleven human embryonic stem cells (hESC) lines were established by nuclear transfer (SCNT; NT) of skin cells from patients with disease or injury into donated oocytes." announced 29 Dec 2005 that he had faked the results.

The journal Science retracted the original paper, the original reference with link to the erratum.[12]

Science News 06 Jan | Special Online Collection: Hwang et al. and Stem Cell Issues

Cancer

There is a hypothesis that several cancers may arise from somatic stem or progenitor cells that exist in different tissues. These cancer stem cells are called "side population" (SP) cells and have been identified in: leukemia, breast cancer and several human cancer cell lines (central nervous system, gastrointestinal tumors, retinoblastoma). There is still a "chicken and egg" problem to be resolved, in that the cancer cells may have dedifferentiated to a stem cell-like population.

A recent paper has also identified SP cells in ovarian cancer which have properties similar to stem cells.[13]

References

  1. <pubmed>19570509</pubmed>
  2. <pubmed>18849962</pubmed>
  3. <pubmed>18391221</pubmed>
  4. <pubmed>16716313</pubmed>
  5. <pubmed>16679411</pubmed>
  6. <pubmed>16446319</pubmed>
  7. <pubmed>16480445</pubmed>
  8. <pubmed>16107472</pubmed>
  9. <pubmed>12493728</pubmed>
  10. <pubmed>18035408</pubmed>
  11. <pubmed>19915522</pubmed>
  12. <pubmed>15905366</pubmed>
  13. <pubmed>16574858</pubmed>

Journals

  • Cell Stem Cell is the official affiliated journal of the International Society for Stem Cell Research (ISSCR).
  • Stem Cells welcomes original articles and concise reviews describing basic laboratory investigations of stem cells and the translation of their clinical aspects of characterization and manipulation from the bench to patient care. The journal covers all aspects of stem cells: embryonic stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell genomics and proteomics; and translational and clinical researc

Reviews

<pubmed>19570509</pubmed> <pubmed>16574858</pubmed> <pubmed>16212509</pubmed>

Articles

<pubmed>16728281</pubmed> <pubmed>16723974</pubmed> <pubmed>16719047</pubmed> <pubmed>16716780</pubmed> <pubmed>16716313</pubmed> <pubmed>16574858</pubmed>

Search PubMed

May 2006 "stem cell" 154,176 reference articles of which 16,449 were reviews.

Search PubMed Now: stem cell | embryonic stem cell | adult stem cell |

Australia

The Australian Health Ethics Committee was approached by human research ethics committees (HRECs) seeking advice on how to review research protocols that involve stem cell research. The following guidance is interim. Formal guidelines will be developed by AHEC in the context of its review of the 1996 NHMRC Ethical guidelines on assisted reproductive technology.

INFORMATION FOR HUMAN RESEARCH ETHICS COMMITTEES SHEET NUMBER 5 - STEM CELL RESEARCH

USA

National Institute of Health (NIH) Stem Cell Information NIH Stem Cell Basics | NIH Stem Cell Information | NIH Stem Cell Reports | Regenerative Medicine 2006 | Stem Cells: Scientific Progress and Future Research Directions (2001) | National Human Genome Research Institute - Cloning/Embryonic Stem Cells

Stem Cell News (2001)

During the earlier Bush administration there was much political controversy about Stem cells in the USA.

External Links

Original UNSW Embryology Pages: Stem Cells | Stem Cell Ethics | Cord Blood | Adult Stem Cells | Neural Stem Cells | Week 2 Stem Cells | Cloning

International Society for Stem Cell Research (ISSCR) is an independent, nonprofit organization formed in 2002 to foster the exchange of information on stem cell research.

University of Michigan Stem Cells Explained

Transcript of discussion on ABC Radio (Dr. J Kahn , Dr. JWagner) on Genetic Technology And Ethics

A brief article on Cord Blood stem cells and their therapeutic potential from the BBC.

Monash University (Australia) [%20http://www.med.monash.edu.au/miscl/ Monash Immunology and Stem Cell Laboratories (MISCL)]

Human Stem cells in the News mainly in regard to USA political position on Human Stem Cell Research (BBC links)

The external link to CNN requires Quicktime Stem Cell Animation === Navigation ===


Glossary Links

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Cite this page: Hill, M.A. (2020, September 21) Embryology Stem Cells - Placental Cord Blood. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Stem_Cells_-_Placental_Cord_Blood

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© Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G