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Posts Tagged ‘Zebrafish model’


Cell Research News – What’s to Follow?

Larry H. Bernstein, MD, FCAP, Reporter

Leaders in Pharmaceutical Intelligence

https://pharmaceuticalintelligence.com/2014/08/26/larryhbern/Cell_Research_News_-_What’s_to_Follow?

 

Stem Cell Research ‘Holy Grail’ Uncovered, Thanks to Zebrafish

By Estel Grace Masangkay

With help from the zebrafish, a team of Australian researchers has uncovered how
hematopoietic stem cells (HSC) renew themselves.

HSCs refers to stem cells present in the blood and bone marrow that are used 
for  the replenishment of the body’s supply of blood and immune cells – 

  • in transplants for leukemia and myeloma.
  • Stem cells have the potential to transform into vital cells

    including muscle, bone, and blood vessels.

Understanding how HSCs form and renew themselves has potential application in the
treatment of

  • spinal cord injuries
  • degenerative disorders
  • diabetes.

Professor Peter Currie, of the Australian Regen Med Institute at Victoria’s Monash
University, led a research team to discover a crucial part of HSC’s development. Using 
a high-resolution microscopy, Prof. Curie’s team 

  • caught zebrafish embyonic SCs on film as they formed. 
  • the researchers were studying muscle mutations in the aquatic animal.

“Zebrafish make ESCs in exactly the same way as humans do, but their embryos and
larvae develop free living, but the larvae are both free swimming and transparent, so one could see every cell in the body forming, including ESCs,” explained Prof. Currie.

The researchers noticed in films that a

  •  ‘buddy cell’ came along to help the ESCs form.

Called endotome cells, 

  • they aided pre-ESCs to turn into ESCs.  

Prof. Currie said that endotome cells act as helper cells for pre-ESCs , 

  • helping them progress to become fully fledged stem cells.

The team not only

  • identified some of the cells and signals 
  • required for ESC formation, but also 
  • pinpointed the genes required 
  • for endotome formation in the first place.

The next step for the researchers is to 

  • locate the signals present in the endotome cells 
  • that trigger ESC formation in the embryo. 

This may provide clues for developing

  • specific blood cells on demand for blood-related disorders. 

Professor Currie also pointed out the discovery’s potential for 

  • correcting genetic defects in the cell and 
  • transplanting them back in the body to treat disorders.

The team’s work was published in the international journal Nature.

 

Jell-O Like Biomaterial Could Hold Key to Cancer Cell Destruction

by Estel Grace Masangkay

Scientists from Penn State University reported that a biomaterial made of tiny 
molecules was able to attract and destroy cancer cells.

Professor Yong Wang and bioengineering faculty at Penn State, built the 
tissue-like biomaterial to accomplish what chemotherapy could not –

  • kill every cancer cell without leaving
  • the possibility of a recurrence.

Prof. Wang and team built polymers 

  • from tiny molecules called monomers. They
  • then wove the polymers into 3D networks 

called hydrogels. Hydrogel is soft and flexible, 
like Jell-O, and it contains a lot of water, and

  • can be safely put into the body, unlike 

other implants that the body often tries 

  • to get rid of through the immune response.

“We want to make sure the materials we are using are compatible in the body.”

The researchers 

  • attached aptamers to the hydrogels, 
  • which release bio-chemical signal-only molecules 
  • that draw in cancer cells. 

Once attracted, the cancer cells are entrapped in the Jell-O-like substance. 

What happens next is 

  • an oligonucleotide binds to the protein-binding site of the aptamer 
  • and triggers the release of anticancer drugs at the proper time.

“Once we trap the cancer cells, we can deliver anticancer drugs 

  • to that specific location to kill them. 

This technique would help avoid the need for systemic medications that kill not only cancer cells, but normal cells as well. Systemic chemotherapy drugs

  • make patients devastatingly sick and possibly 
  • leave behind cancer cells to wreak havoc another day

If our new technique has any side effects at all, it would be only local side 
effects and not whole-body systemic side effects,” explained Prof. Wang.

The initial results of the research were published by Prof. Wang in the 
Journal of the American Chemical Society in 2012. Prof. Wang also shared 
the latest results of his work at the Society for Biomaterials Meeting &
 Exposition in April this year.

 

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Zebrafish Study Tool

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

 

The following recent report is of interest to biological modeling in cancer, cardiovascular, immune-mediated and metabolic diseases.  The method duplicates genetic variants related to the disease in specifically craniofacial disorders in people transfected into the Zebrafish, but it has a potential to be extended to other diseases.

New Zebrafish Study Tool Looks Promising for Human Disease Research

Scientists at Duke University say they have connected rare and precise duplications and deletions in the human genome to their complex disease consequences by duplicating them in zebrafish. The findings are based on studies of five people missing a small fragment of their genome and suffering from a mysterious syndrome of craniofacial features, visual anomalies, and developmental delays, according to the researchers.

When those patient observations were coupled to analyses of the anatomical defects in genetically altered zebrafish embryos,

  • the investigators were able to identify the contribution specific genes made to the pathology.
  • They believe they have developed a new tool that can now be applied to unraveling many other complex and rare human genetic conditions.

The findings are published in the research article titled –

SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q23.4 Copy-Number Variant

The findings are broadly important for human genetic disorders because

  • copy-number variants (CNVs), which are fragments of the genome that are either missing or existing in extra copies, are quite common.

The precise contribution to diseases causation  has been difficult to determine because

  • CNVs can affect the function of many genes simultaneously.

“Because a CNV can perturb many genes, it is difficult to know which of them is responsible,” said Nicholas Katsanis, Ph.D., a professor of cell biology who directs the Center for Human Disease Modeling and the Task Force for Neonatal Genomics at Duke.

Last year, Dr. Katsanis and his team found

  • they could trace recurrent copy-number variants and
  • dissect the consequences of each perturbed gene to particular features in patients.

The new study goes one step further by showing that they can also do this in more challenging cases, when CNVs differ in size from one individual to the next. In this case, “each person has his or her own private deletion or duplication,” added Dr. Katsanis, with the potential to affect a different number of genes.

The researchers showed that partially overlapping microdeletions found in the human patients include a region that contains three genes. By manipulating those genes in zebrafish,

  • first one at a time and then
  • in combination,

they were able to connect the genes to specific features of the human syndrome.

“Fine mapping localized a commonly deleted 78 kb region that contains three genes: SCRIB, NRBP2, and PUF60,” write the researchers in the American Journal of Human Genetics. “In vivo dissection of the CNV showed

  • discrete contributions of the planar cell polarity effector SCRIB and
  • the splicing factor PUF60 to the syndromic phenotype, and
  • the combinatorial suppression of both genes exacerbated some, but not all, phenotypic components.

Consistent with these findings, we identified an individual with microcephaly, short stature, intellectual disability, and heart defects with a de novo c.505C>T variant leading to a p.His169Tyr change in PUF60.”

In principle, the Duke group says they can now examine the role of copy-number variants in any human syndrome,

  • so long as the condition is associated with features that are measurable in the fish.

“We will need to study lots of CNVs to find the edges of our capabilities,” explained Dr. Katsanis. “As we add this layer of dissection and interpretation, we will have prediction, diagnosis, and the beginnings of biological understanding.”

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