Stem Cells

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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[1]

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.

NIH Information

A useful guide (online PDF document) to stem cells was produced in a report by the National Institute of Health (NIH, USA, April 2009) Stem Cells: A Primer (PDF 1.89 MB) and more recently NIH has established a Stem Cell information page.

Stem Cells: NIH 2009 Primer | File:NIH Regenerative Medicine 2006.pdf | 2001 Primer | NIH Stem Cell Basics | 2009 NIH Report | Regenerative Medicine 2006 | 2001 NIH Report


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

Human stem cell pancreas implants
Human stem cell pancreas implants[2]
human blastocyst
Stem cell artificial trachea and bronchi (Image UCL)
  • Distinct SoxB1 networks are required for naïve and primed pluripotency[3] "Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency." Sox
  • Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice[2] "The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue. The latter concern may be addressed by recently described glucose-responsive mature beta cells that are derived from human embryonic stem cells (referred to as SC-β cells), which may represent an unlimited source of human cells for pancreas replacement therapy. ...human SC-β cells were encapsulated with alginate derivatives capable of mitigating foreign-body responses in vivo and implanted into the intraperitoneal space of C57BL/6J mice treated with streptozotocin, which is an animal model for chemically induced type 1 diabetes. These implants induced glycemic correction without any immunosuppression until their removal at 174 d after implantation. Human C-peptide concentrations and in vivo glucose responsiveness demonstrated therapeutically relevant glycemic control. Implants retrieved after 174 d contained viable insulin-producing cells."
  • Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1[4] "Haematopoietic stem cells (HSCs) are self-renewing stem cells capable of replenishing all blood lineages. In all vertebrate embryos that have been studied, definitive HSCs are generated initially within the dorsal aorta (DA) of the embryonic vasculature by a series of poorly understood inductive events. Previous studies have identified that signalling relayed from adjacent somites coordinates HSC induction, but the nature of this signal has remained elusive. Here we reveal that somite specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the zebrafish somite that we have defined as the endotome. Endothelial cells of the endotome are specified within the nascent somite by the activity of the homeobox gene meox1. Specified endotomal cells consequently migrate and colonize the DA, where they induce HSC formation through the deployment of chemokine signalling activated in these cells during endotome formation." Blood Development
More recent papers  
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Older papers  
  • Generation of organized germ layers from a single mouse embryonic stem cell[5] "Mammalian inner cell mass cells undergo lineage-specific differentiation into germ layers of endoderm, mesoderm and ectoderm during gastrulation. It has been a long-standing challenge in developmental biology to replicate these organized germ layer patterns in culture. Here we present a method of generating organized germ layers from a single mouse embryonic stem cell cultured in a soft fibrin matrix." Gastrulation
  • Derivation of naive human embryonic stem cells[6] "We show that human naïve cells meet mouse criteria for the naïve state by growth characteristics, antibody labeling profile, gene expression, X-inactivation profile, mitochondrial morphology, microRNA profile and development in the context of teratomas. hESCs can exist in a naïve state without the need for transgenes. Direct derivation is an elusive, but attainable, process, leading to cells at the earliest stage of in vitro pluripotency described for humans. Reverse toggling of primed cells to naïve is efficient and reproducible."
  • Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer [7] 1. Cytoplasm of human oocytes reprograms transplanted somatic cell nuclei to pluripotency. 2. NT-ESCs can be efficiently derived from high-quality human oocytes 3. Human NT-ESCs are similar to ESCs derived from fertilized embryos. Nature comment - Human stem cells created by cloning
  • The Nobel Prize in Physiology or Medicine 2012 was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka "for the discovery that mature cells can be reprogrammed to become pluripotent" Shinya Yamanaka Yamanaka Factors are a set of 4 transcription factors when introduced into cells induces stem cell formation. John Gurdon used nuclear transplantation and cloning to show that the nucleus of a differentiated somatic cell retains the totipotency necessary to form a whole organism. Induced Stem Cells
  • Nature Cell Biology Focus on stem cells "This issue presents a series of specially commissioned articles that highlight exciting facets of stem cell research, including recent insights into the nature of pluripotency and how studying stem cells can increase our understanding of normal ageing and disease." Editorial
  • First Successful Transplantation of a Synthetic Tissue Engineered Windpipe Karolinska Institute | University College London | BBC News "An international team designed and built the nanocomposite tracheal scaffold and produced a specifically designed bioreactor used to seed the scaffold with the patient´s own stem cells. The cells were grown on the scaffold inside the bioreactor for two days before transplantation to the patient. Because the cells used to regenerate the trachea were the patient's own, there has been no rejection of the transplant and the patient is not taking immunosuppressive drugs."
  • Culture of human pluripotent stem cells using completely defined conditions on a recombinant E-cadherin substratum[8] "huES and human induced pluripotent stem (hiPS) cells were grown on plates coated with a fusion protein consisting of E-cadherin and the IgG Fc domain using mTeSR1 medium. Cells grown under these conditions maintained similar morphology and growth rate to those grown on Matrigel and retained all pluripotent stem cell features, including an ability to differentiate into multiple cell lineages in teratoma assays."
  • Epigenetic memory in induced pluripotent stem cells.[9] "Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment."

Embryonic Stem Cell

Human blastocyst derived stem cells.jpg

Mesenchymal Stem Cells

Recently the human GA 14 to 16 weeks fetal heart have been used as a source of mesenchymal stem cells that appear similar to human bone marrow mesenchymal stem cells (expressing CD73, CD90, CD105 and lacking expression of CD31, CD34, CD45, HLA-DR).[10]


Human blastocyst derived stem cells[11]

(A–D) - stepwise procedure of embryo biopsy using inverted microscope-attached micro manipulator.

(E–L) - appearance of initial outgrowth and hESC colony during the derivation procedure.

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

Links: Stem Cells - Placental Cord Blood

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.[12]
  • Spermatogonial stem cells: questions, models and perspectives.[13]Cite error: Closing </ref> missing for <ref> tag

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.[14]

References

  1. Li J, Greco V, Guasch G, Fuchs E & Mombaerts P. (2007). Mice cloned from skin cells. Proc. Natl. Acad. Sci. U.S.A. , 104, 2738-43. PMID: 17299040 DOI.
  2. 2.0 2.1 Vegas AJ, Veiseh O, Gürtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, Tam HH, Jhunjhunwala S, Langan E, Aresta-Dasilva S, Gandham S, McGarrigle JJ, Bochenek MA, Hollister-Lock J, Oberholzer J, Greiner DL, Weir GC, Melton DA, Langer R & Anderson DG. (2016). Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat. Med. , 22, 306-11. PMID: 26808346 DOI.
  3. Corsinotti A, Wong FC, Tatar T, Szczerbinska I, Halbritter F, Colby D, Gogolok S, Pantier R, Liggat K, Mirfazeli ES, Hall-Ponsele E, Mullin NP, Wilson V & Chambers I. (2017). Distinct SoxB1 networks are required for naïve and primed pluripotency. Elife , 6, . PMID: 29256862 DOI.
  4. Nguyen PD, Hollway GE, Sonntag C, Miles LB, Hall TE, Berger S, Fernandez KJ, Gurevich DB, Cole NJ, Alaei S, Ramialison M, Sutherland RL, Polo JM, Lieschke GJ & Currie PD. (2014). Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1. Nature , 512, 314-8. PMID: 25119043 DOI.
  5. Poh YC, Chen J, Hong Y, Yi H, Zhang S, Chen J, Wu DC, Wang L, Jia Q, Singh R, Yao W, Tan Y, Tajik A, Tanaka TS & Wang N. (2014). Generation of organized germ layers from a single mouse embryonic stem cell. Nat Commun , 5, 4000. PMID: 24873804 DOI.
  6. Ware CB, Nelson AM, Mecham B, Hesson J, Zhou W, Jonlin EC, Jimenez-Caliani AJ, Deng X, Cavanaugh C, Cook S, Tesar PJ, Okada J, Margaretha L, Sperber H, Choi M, Blau CA, Treuting PM, Hawkins RD, Cirulli V & Ruohola-Baker H. (2014). Derivation of naive human embryonic stem cells. Proc. Natl. Acad. Sci. U.S.A. , 111, 4484-9. PMID: 24623855 DOI.
  7. Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer Cell May 2013.
  8. Nagaoka M, Si-Tayeb K, Akaike T & Duncan SA. (2010). Culture of human pluripotent stem cells using completely defined conditions on a recombinant E-cadherin substratum. BMC Dev. Biol. , 10, 60. PMID: 20525219 DOI.
  9. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, McKinney-Freeman S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Murakami P, Jaenisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP & Daley GQ. (2010). Epigenetic memory in induced pluripotent stem cells. Nature , 467, 285-90. PMID: 20644535 DOI.
  10. Garikipati VNS, Singh SP, Mohanram Y, Gupta AK, Kapoor D & Nityanand S. (2018). Isolation and characterization of mesenchymal stem cells from human fetus heart. PLoS ONE , 13, e0192244. PMID: 29420637 DOI.
  11. Giritharan G, Ilic D, Gormley M & Krtolica A. (2011). Human embryonic stem cells derived from embryos at different stages of development share similar transcription profiles. PLoS ONE , 6, e26570. PMID: 22039509 DOI.
  12. Kanatsu-Shinohara M, Ikawa M, Takehashi M, Ogonuki N, Miki H, Inoue K, Kazuki Y, Lee J, Toyokuni S, Oshimura M, Ogura A & Shinohara T. (2006). Production of knockout mice by random or targeted mutagenesis in spermatogonial stem cells. Proc. Natl. Acad. Sci. U.S.A. , 103, 8018-23. PMID: 16679411 DOI.
  13. Ehmcke J, Wistuba J & Schlatt S. (2006). Spermatogonial stem cells: questions, models and perspectives. Hum. Reprod. Update , 12, 275-82. PMID: 16446319 DOI.
  14. Moore KA & Lemischka IR. (2006). Stem cells and their niches. Science , 311, 1880-5. PMID: 16574858 DOI.

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

Trounson A & DeWitt ND. (2016). Pluripotent stem cells progressing to the clinic. Nat. Rev. Mol. Cell Biol. , 17, 194-200. PMID: 26908143 DOI.

Mathews DJ, Donovan PJ, Harris J, Lovell-Badge R, Savulescu J & Faden R. (2009). Pluripotent stem cell-derived gametes: truth and (potential) consequences. Cell Stem Cell , 5, 11-4. PMID: 19570509 DOI.

Moore KA & Lemischka IR. (2006). Stem cells and their niches. Science , 311, 1880-5. PMID: 16574858 DOI.

Li L & Xie T. (2005). Stem cell niche: structure and function. Annu. Rev. Cell Dev. Biol. , 21, 605-31. PMID: 16212509 DOI.

Articles

Pekkanen-Mattila M, Pelto-Huikko M, Kujala V, Suuronen R, Skottman H, Aalto-Setälä K & Kerkelä E. (2010). Spatial and temporal expression pattern of germ layer markers during human embryonic stem cell differentiation in embryoid bodies. Histochem. Cell Biol. , 133, 595-606. PMID: 20369364 DOI.

Hiroyama T, Miharada K, Aoki N, Fujioka T, Sudo K, Danjo I, Nagasawa T & Nakamura Y. (2006). Long-lasting in vitro hematopoiesis derived from primate embryonic stem cells. Exp. Hematol. , 34, 760-9. PMID: 16728281 DOI.

Meshorer E & Misteli T. (2006). Chromatin in pluripotent embryonic stem cells and differentiation. Nat. Rev. Mol. Cell Biol. , 7, 540-6. PMID: 16723974 DOI.

Yamazoe H, Kobori M, Murakami Y, Yano K, Satoh M, Mizuseki K, Sasai Y & Iwata H. (2006). One-step induction of neurons from mouse embryonic stem cells in serum-free media containing vitamin B12 and heparin. Cell Transplant , 15, 135-45. PMID: 16719047

Skottman H, Dilber MS & Hovatta O. (2006). The derivation of clinical-grade human embryonic stem cell lines. FEBS Lett. , 580, 2875-8. PMID: 16716780 DOI.

Hammarberg K & Tinney L. (2006). Deciding the fate of supernumerary frozen embryos: a survey of couples' decisions and the factors influencing their choice. Fertil. Steril. , 86, 86-91. PMID: 16716313 DOI.

Moore KA & Lemischka IR. (2006). Stem cells and their niches. Science , 311, 1880-5. PMID: 16574858 DOI.

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

Stem Cells: NIH 2009 Primer | File:NIH Regenerative Medicine 2006.pdf | 2001 Primer | NIH Stem Cell Basics | 2009 NIH Report | Regenerative Medicine 2006 | 2001 NIH Report

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

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Cite this page: Hill, M.A. (2024, March 28) Embryology Stem Cells. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Stem_Cells

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