Stem Cells

 

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Stem cells have an interesting history that has been somewhat tainted with debate and controversy. In the mid-1800s it was discovered that cells were basically the building blocks of life and that some cells had the ability to produce other cells. Attempts were made to fertilize mammalian eggs outside of the human body and in the early 1900s, it was discovered that some cells had the ability to generate blood cells. In 1968, the first bone marrow transplant was performed to successfully treat two siblings with severe combined immunodeficiency. Other key events in stem cell research include:

 

a. 1978: Stem cells were discovered in human cord blood

b. 1981: First in vitro stem cell line developed from mice

c. 1988: Embryonic stem cell lines created from a hamster

d. 1995: First embryonic stem cell line derived from a primate

e. 1997: Cloned lamb from stem cells

f. 1997: Leukemia origin found as hematopoietic stem cell, indicating possible proof of cancer stem cells

 

In 1998, Thompson, from the University of Wisconsin, isolated cells from the inner cell mass of early embryos and developed the first embryonic stem cell lines. During that same year, Gearhart, from Johns HopkinsUniversity, derived germ cells from cells in fetal gonad tissue; pluripotent stem cell lines were developed from both sources. Then, in 1999 and 2000, scientists discovered that manipulating adult mouse tissues could produce different cell types. This meant that cells from bone marrow could produce nerve or liver cells and cells in the brain could also yield other cell types. These discoveries were exciting for the field of stem cell research, with the promise of greater scientific control over stem cell differentiation and proliferation.

 

Below are a few research achievements, that show a history of stem cell research over the past 100 years:

 

1908: The term “stem cell” was proposed for scientific use by the Russian histologist Alexander Maksimov (1874-1928) at congress of hematologic society in Berlin. It postulated existence of hematopoietic stem cells.

 

1960s: Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; their reports contradict Cajal’s “no new neurons” dogma and are largely ignored.

 

1963: McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.

 

1968: Bone marrow transplant between two siblings successfully treats SCID.

 

1978: Hematopoietic stem cells are discovered in human cord blood.

 

1981: Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term “Embryonic Stem Cell”.

 

1992: Neural stem cells are cultured in vitro as neurospheres.

 

1995: Dr. B.G. Matapurkar pioneers in adult stem-cell research with clinical utilization of research in the body and neo-regeneration of tissues and organs in the body. Received International Patent from US Patent Office (USA) in 2001 (effective from 1995). Clinical utilization in human body also demonstrated and patented in 60 patients (World Journal of Surgery-1999 and 1991).

 

1997: Dr. B.G. Matapurkar’s surgical technique on regeneration of tissues and organs is published. Regeneration of fallopian tube and uterus is published.

 

1997: Leukemia is shown to originate from a hematopoietic stem cell, the first direct evidence for cancer stem cells.

 

1998: James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin-Madison.

 

1998: John Gearhart (Johns Hopkins University) extracted germ cells from fetal gonadal tissue (primordial germ cells) before developing pluripotent stem cell lines from the original extract.

 

2000s: Several reports of adult stem cell plasticity are published.

 

2001: Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.

 

2003: Dr. Songtao Shi of NIH discovers new source of adult stem cells in children’s primary teeth.

 

2005: Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.

 

2005: Researchers at UC Irvine’s Reeve-Irvine Research Center are able to partially restore the ability of rats with paralyzed spines to walk through the injection of human neural stem cells.

 

 

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Yong Zhao, University of Illinois at Chicago

 

April 2006 Scientists at the University of Illinois at Chicago identified cells from the umbilical cord blood with embryonic and hematopoietic characteristics.

 

August 2006: Mouse Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka.

 

November 2006: Yong Zhao et al. revealed the immune regulation of T lymphocytes by Cord Blood-Derived Multipotent Stem Cells (CB-SCs).

 

October 2006: Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells.

 

January 2007: Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard report discovery of a new type of stem cell in amniotic fluid. This may potentially provide an alternative to embryonic stem cells for use in research and therapy.

 

June 2007: Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice. In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer

 

 

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Martin Evans, a co-winner of the Nobel Prize in recognition of his gene targeting work.

 

October 2007: Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.

 

November 2007: Human induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, “Induction of pluripotent stem cells from adult human fibroblasts by defined factors”, and in Science by Junying Yu, et al., from the research group of James Thomson, “Induced pluripotent stem cell lines derived from human somatic cells”: pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.

 

January 2008: Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo

 

January 2008: Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts

 

February 2008: Generation of pluripotent stem cells from adult mouse liver and stomach: these iPS cells seem to be more similar to embryonic stem cells than the previously developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques.

 

March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by clinicians from Regenerative Sciences

 

October 2008: Sabine Conrad and colleagues at Tubingen, Germany generate pluripotent stem cells from spermatogonial cells of adult human testis by culturing the cells in vitro under leukemia inhibitory factor (LIF) supplementation.

 

30 October 2008: Embryonic-like stem cells from a single human hair.

 

January 2009: Yong Zhao and colleagues confirmed the reversal of autoimmune-caused type 1 diabetes by Cord Blood-Derived Multipotent Stem Cells (CB-SCs) in an animal experiment.

 

1 March 2009: Andras Nagy, Keisuke Kaji, et al. discover a way to produce embryonic-like stem cells from normal adult cells by using a novel “wrapping” procedure to deliver specific genes to adult cells to reprogram them into stem cells without the risks of using a virus to make the change. The use of electroporation is said to allow for the temporary insertion of genes into the cell.

 

28 May 2009 Kim et al. announced that they had devised a way to manipulate skin cells to create patient specific “induced pluripotent stem cells” (iPS), claiming it to be the ‘ultimate stem cell solution’.

 

11 October 2010 First trial of embryonic stem cells in humans.

 

25 October 2010: Ishikawa et al. write in the Journal of Experimental Medicine that research shows that transplanted cells that contain their new host’s nuclear DNA could still be rejected by the individual’s immune system due to foreign mitochondrial DNA. Tissues made from a person’s stem cells could therefore be rejected, because mitochondrial genomes tend to accumulate mutations.

 

2011: Israeli scientist Inbar Friedrich Ben-Nun led a team which produced the first stem cells from endangered species, a breakthrough that could save animals in danger of extinction.

 

January 2012: The human clinical trial of treating type 1 diabetes with lymphocyte modification using Cord Blood-Derived Multipotent Stem Cells (CB-SCs) achieved an improvement of C-peptide levels, reduced the median glycated hemoglobin A1C (HbA1c) values, and decreased the median daily dose of insulin in both human patient groups with and without residual beta cell function. Yong Zhao’s Stem Cell Educator Therapy appears “so simple and so safe”

 

October 2012: Positions of nucleosomes in mouse embryonic stem cells and the changes in their positions during differentiation to neural progenitor cells and embryonic fibroblasts are determined with single-nucleotide resolution.

 

2012: Katsuhiko Hayashi used mouse skin cells to create stem cells and then used these stem cells to create mouse eggs. These eggs were then fertilized and produced healthy baby offspring. These latter mice were able to have their own babies.

 

2013: First time lab grown meat made from muscle stem-cells has been cooked and tasted.

 

2013: First time mice adult cells were reprogrammed into stem cells in vivo.

 

2013: Scientists at Scotland’s Heriot-Watt University developed a 3D printer that can produce clusters of living human embryonic, potentially allowing complete organs to be printed on demand in the future.

 

2014: Adult mouse cells reprogrammed to pluripotent stem cells using stimulus-triggered acquisition of pluripotency (STAP); a process which involved bathing blood cells in an acid bath (pH 5.7) for 30minutes at 37 ?C.

 

In early 2007, researchers led by Dr. Anthony Atala discovered a new type of stem cell isolated in amniotic fluid. This finding is particularly important because these stem cells could prove to be a viable alternative to the controversial use of embryonic stem cells. Over the last few years, national policies and debate amongst the public as well as religious groups, government officials and scientists have led to various laws and procedures regarding stem cell harvesting, development and treatment for research or disease purposes. The goals of such policies are to safeguard the public from unethical stem cell research and use while still supporting new advancements in the field.

 

In March 2009, President Barack Obama reversed a Bush-era policy which had limited funding of embryonic stem cell research and pledged to develop “strict guidelines” on the research. Under Obama, stem cell research has flourished. Stem cell research has now progressed dramatically and there are countless research studies published each year in scientific journals. Adult stem cells are already being used to treat many conditions such as heart disease and leukemia. Researchers still have a long way to go before they completely control the regulation of stem cells. The potential is overwhelmingly positive and with continued support and research, scientists will ideally be able to harness the full power of stem cells to Treat Diseases that you or a loved one may suffer from one day. Sources:  Cell.com; NIH.gov; Wikipedia

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