Rewinding Development

A step forward for stem cell research

Thursday, 06 June 2013

Scientists at the Danish Stem Cell Center, DanStem, at the University of Copenhagen have discovered that they can make embryonic stem cells regress to a stage of development where they are able to make placenta cells as well as the other foetal cells. This significant discovery, published in the journal Cell Reports today, has the potential to shed new light on placenta related disorders that can lead to problematic pregnancies and miscarriages.

The picture shows a 9.5-day-old mouse
embryo including extra-embryonic tissue.
The red region marks embryonic stem cells
in the extra-embryonic yolk sac. Embryonic
stem cells are not normally able to do this,
but when cells are pushed backwards in
development as described in Morgani et al..
Credit: Sophie Morgani, University of
Copenhagen. 

Embryonic stem cells can make all kinds of adult cells in the human body such as muscle, blood or brain cells. However, these embryonic stem cells are created at a point when the embryo has already lost the ability to make extra-embryonic tissue such as placenta and yolk sac. Extra-embryonic tissues are formed at the very earliest stage of development right after fertilization and are essential for the growth of the embryo and its implantation in the womb.

A team of scientists at the Danish Stem Cell Center, DanStem, at the University of Copenhagen have shown that it is possible to rewind the developmental state of embryonic stem cells. By maintaining mouse embryonic stem cells under certain conditions, they found that cells appear to regress and resemble extremely early embryo cells that can form any kind of cell including placenta and yolk sac cells.

"It was a very exciting moment when we tested the theory," says Professor Josh Brickman from DanStem.

"We found that not only can we make adult cells but also placenta, in fact we got precursors of placenta, yolk sac as well as embryo from just one cell."

"This new discovery is crucial for the basic understanding of the nature of embryonic stem cells and could provide a way to model the development of the organism as a whole, rather than just the embryonic portion. In this way we may gain greater insight into conditions where extra-embryonic development is impaired, as in the case of miscarriages," added Sophie Morgani, PhD student at DanStem and first author of the paper.

LIF protein plays a crucial role

Brickman and colleagues grew their embryonic stem cells in a solution containing LIF, which is a protein known to somehow support embryonic stem cells but also for its role in implantation of the embryo into the uterus. As implantation is stimulated by the cells that will become the placenta, not the embryo, these roles appeared to be contradictory. The DanStem study resolved this contradiction by revealing that LIF helps maintain the cells in their regressed, early stage of development.

"In our study we have been able to see the full picture unifying LIF's functions: What LIF really does, is to support the very early embryo state, where the cells can make both embryonic cells and placenta. This fits with LIFs' role in supporting implantation," Josh Brickman says.

Source: University of Copenhagen 

Contact: Joshua Brickman

Reference:

Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions

Sophie M. Morgani, Maurice A. Canham, Jennifer Nichols, Alexei A. Sharov, Rosa Portero Migueles, Minoru S.H. Ko, and Joshua M. Brickman
Cell Reports, 06 June 2013, 10.1016/j.celrep.2013.04.034

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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Placental Stem Cells and Lung Disease

Placenta-derived stem cells may help sufferers of lung diseases Tuesday, 28 July 2009 An Italian research team, publishing in the current issue of Cell Transplantation (18:4), has found that stem cells derived from human placenta may ultimately play a role in the treatment of lung diseases, such as pulmonary fibrosis and fibrotic diseases caused by tuberculosis, chemical exposure, radiation or pathogens. These diseases can ultimately lead to loss of normal lung tissue and organ failure. No known therapy effectively reverses or stops the fibrotic process. Placenta-derived stem cells are known to be able to engraft in solid organs, including the lungs. Human term placenta stem cells also demonstrate characteristics of high plasticity and low immunogenicity. "The potential application of foetal membrane-derived cells as a therapeutic tool for disorders characterized by inflammation and fibrosis is supported in previous studies," says Dr. Ornella Parolini, the study's lead author. "In line with the hypothesis that cells derived from the amniotic membrane have immunomodulatory properties and have been used as an anti-inflammatory agent, we set out to evaluate the effects of foetal membrane-derived cell transplantation in chemically-treated (bleomycin) mice." According to Dr. Parolini, cells delivered via intra-peritoneal transplant, regardless of the cells being allogeneic or xenogeneic (host's own cells or from another individual respectively), the procedure resulted in a significant anti-fibrotic effect on the lab animals. A "consistent" reduction in lung fibrosis, says Dr. Parolini, "provides convincing proof" that placenta-derived cells do confer benefits for bleomycin-induced lung injury. While the severity of inflammation did not show an overall reduction, there was a marked reduction in neutrophil (white blood cell) infiltration after both xeno-and-allo-transplantation. "It is worth noting," says Dr. Parolini, "that the presence of neutrophils is associated with poor prognosis for several lung diseases. However, the mechanism by which placenta-derived cells might affect infiltration by neutrophils is not known." The researchers speculated that these cells may produce soluble factors that induce anti-inflammatory effects. "Our findings suggest that foetal membrane-derived cells may prove useful for cell therapy of fibrotic diseases in the future," concludes Dr. Parolini. Dr. Cesar Borlongan, of the University of South Florida and associate editor for Cell Transplantation, notes that the present study adds an important application of placenta cells, indicating their therapeutic effects in lung diseases. The cells' ability to reduce neutrophils possibly via secreted anti-inflammatory factors implies their use either as autografts or allografts, thereby increasing the numbers of the target patient population. Reference: Transplantation of Allogeneic and Xenogeneic Placenta-Derived Cells Reduces Bleomycin-Induced Lung Fibrosis Authors: Cargnoni, Anna; Gibelli, Lucia; Tosini, Alessandra; Signoroni, Patrizia Bonassi; Nassuato, Claudia; Arienti, Davide; Lombardi, Guerino; Albertini, Alberto; Wengler, Georg S.; Parolini, Ornella Cell Transplantation, Volume 18, Number 4, 2009 , pp. 405-422(18) ......... ZenMaster

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For more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/ and http://www.geocities.com/giantfideli/index.html

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Placenta: New Source for Harvesting Stem Cells

Children's Hospital Oakland scientists first to discover new source for harvesting stem cells Tuesday, 23 June 2009 A groundbreaking study conducted by Children's Hospital & Research Center at Oakland, California, is the first to reveal a new avenue for harvesting stem cells from a woman's placenta, or more specifically the discarded placentas of healthy newborns. The study also finds there are far more stem cells in placentas than in umbilical cord blood, and they can be safely extracted for transplantation. Furthermore, it is highly likely that placental stem cells, like umbilical cord blood and bone marrow stem cells, can be used to cure chronic blood-related disorders such as sickle cell disease, thalassaemia, and leukaemia. The study, led by Children's Hospital & Research Center Oakland scientists Frans Kuypers, PhD, and Vladimir Serikov, PhD, will be the feature story in the July 2009 issue of Experimental Biology and Medicine. The doctors and their team made the discoveries by harvesting term placentas from healthy women undergoing elective Caesarean sections. "Yes, the stem cells are there; yes, they are viable; and yes, we can get them out," declared Dr. Kuypers. Stem cells are essentially blank cells that can be transformed into any type of cell such as a muscle cell, a brain cell, or a red blood cell. Using stem cells from umbilical cord blood, Children's Hospital Oakland physicians have cured more than 100 kids with chronic blood-related diseases through their sibling donor cord blood transplantation program, which began in 1997. However, according to the American Cancer Society, each year at least 16,000 people with serious blood- related disorders are not able to receive the bone marrow or cord blood transplant they need because they cannot find a match. Dr. Kuypers explained that even when a patient receives a cord blood transplant, there may not be enough stem cells in the umbilical cord to successfully treat their disorder. Placentas, however, contain several times more stem cells than umbilical cord blood. "The greater supply of stem cells in placentas will likely increase the chance that an HLA (human leukocyte antigen) matched unit of stem cells engrafts, making stem cell transplants available to more people. The more stem cells, the bigger the chance of success," said Dr. Kuypers.

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This is a microphotograph of chorionic villus of human term placenta immunostained for CD34 (Marker of endothelial and haematopoietic stem cells, red), CD31 (marker of endothelial cell, green) and nuclei (DAPI, blue). Non-endothelial CD34-positive cell is clearly observed in tissue of placenta. Credit: Society for Experimental Biology and Medicine.

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In this report, said Dr. Serikov, we demonstrate for the first time that human placentas could provide abundant amounts of CD34+ CD133+ colony-forming cells, as well as other primitive hematopoietic progenitors, suitable for transplantation in humans. The total amount of live haematopoietic stem cells, or colony-forming units in culture that could be obtained from placentas was an order of magnitude larger than the number of hematopoietic stem cells obtained from cord blood from the same source. Haematopoietic stem cells which maintain their differentiation capacity, as well as stromal stem cells that support long-term culture of haematopoietic cells, can be harvested from perfusate of placenta following CXCR4 receptor blockade, said Dr. F. Kuypers. Importantly, live HPCs can similarly be obtained from whole cryopreserved placentas. Cells derived from placental tissue differentiated into all blood lineages in vitro. Animal experiments further demonstrated successful engraftment of placenta-derived HSC, which reconstituted haematopoiesis in immunodeficient mice. In summary, said Dr. F. Kuypers, our results indicate for the first time that human term placenta is a high capacity source of live and functional hematopoietic stem cells. By using placental circulation and stem cell receptor blockade an abundant amounts of hematopoietic stem cell could be easily obtained in sterile conditions by non-destructive methods. Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "the outstanding importance of these results for practical haematology is determined by the fact that total number of stem cells that can be harvested from cord blood limits the efficacy of this stem cell source for transplants only to small children. These novel findings demonstrate that placenta may provide a source of autologous stem cells sufficient for reconstitution of haematopoiesis in adult patients. Use of methods to obtain haematopoietic cells from placenta, developed by Dr. Serikov and Dr. Kuypers as augmentation of cord blood-based therapy or replacement of bone marrow for transplantation will dramatically change whole field of transplantology." Drs. Kuypers and Serikov have also developed a patent-pending method that will allow placental stem cells to be safely harvested and made accessible for transplantation. The process involves freezing placentas in a way that allows them to later be defrosted and suffused with a compound that enables the extraction of viable stem cells. The method will make it possible for companies to gather, ship and store placentas in a central location. "We're looking for a partnership with industry to get placenta-derived stem cells in large quantities to the clinic," said Dr. Kuypers. He adds that much more research and grant funding are needed to explore the maximum potential of this latest discovery. He remains encouraged. "Someday, we will be able to save a lot more kids and adults from these horrific blood disorders." ......... ZenMaster

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For more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/ and http://www.geocities.com/giantfideli/index.html

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