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Regenerative Medicine: Group Presentation

Group informative presentation about regenerative medicine, including emphases on stem cells, tissue engineering, and xenotransplantation.
by

Nick Lorang

on 12 December 2013

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Transcript of Regenerative Medicine: Group Presentation

Nicholas Lorang, Jonah DeVries,
Elizabeth Yosick, Kaya Borg, Gabrielle Suda

Regenerative Medicine
the branch of medicine concerned with repairing and/or regrowing tissues and organs.
Regenerative Medicine is...
The process of creating functional tissues to repair or replace organs or tissues that were lost

An emerging field that is focused on restoring impaired functions of tissues, cells or organs

Currently untreatable diseases could eventually be treated using regenerative medicine

Ancient Greece

Prometheus and Ethos the Eagle
Regeneration of the Liver
16th Century
Tissue Grafting, Cosmas and Damien
Legs of moors
1901
Regenerative research by Thomas Morgan
Frog eggs
Question of how cells can regenerate a whole organism
Did theoretical research on regeneration of hydra, worms, frogs, and planarians
1907
Stem Cell experimentation by Ross Harrison
1920s
Induction and Cloning research

1951
Successful cloning of frog eggs by Robert Briggs and Thomas King

John Gurdon, at the same time, demonstrated that in later stages of the frogs development, the frogs could produce cloned adults by donating nuclei

1956
C. H. Waddington found evidence to support that regeneration involves dedifferentiation

1981

First stem cells in a mouse cell generated by Martin Evans and Gail Martin

1998
James Thomas developed primate stem cell line and human stem cell line

STEM CELLS
TISSUE ENGINEERING
XENOTRANSPLANT
Stem Cells...
are cells that are capable of differentiating into numerous different types of body cells

Stem cells are one way of using the body's own mechanisms to help heal itself.
Stem cells can be categorized in multiple ways:
...by origin
Embryonic
Adult


...by versatility/function
Embryonic stem cells
are those taken from the embryo or its environment during pregnancy or childbirth.

They can come from a days-old blastocyte, amniotic fluid, placenta, umbilical cord blood, or umbilical cord tissue.
The Process
In vitro fertilization produces multiple embryos. Those that are not used, if donated, can be used as a source of stem cells, rather than being disposed of.

The stem cells are extracted and cultured with growth factors specific to whatever type of cell is desired.

Stem cells can also be harvested from umbilical cord blood or cord tissue at the time of birth and stored.
Alternatively,
research is being done into methods of stem cell extraction that do not sacrifice the embryo.

By adding three specific genes to an adult somatic cell, scientists are able to "create" a stem cell from a body cell, resulting in stem cells highly similar to embryonic stem cells.
Adult stem cells
are found naturally in the body, because they help repair the tissue in which they are found.


They can be obtained from bone marrow, developing tooth buds, and several other body tissues.

Much research is currently being done to investigate the properties of adult stem cells.

Because they are havested directly from the patient, there is virtually no risk of rejection.

The use of adult stem cells is far less controversial than embryonic stem cells, because they are not taken from terminal embryos.
Different kinds of stem cells have differing levels of
potency
(versatility; ability to differentiate into different types).
After about 4 days, the
inner cell mass is
pluripotent
.
Pluripotent
The capacity of the human zygote to differentiate into all possible cell types is called
totipotency
.
The majority of stem cells that are used in research are
pluripotent
(highly versatile).

Induced pluripotency
is when
adult somatic cells are reprogrammed
into highly versatile stem cells.

Unfortunately, there is worry that this
may lead to increased risk for tumors.
Multipotent
Many stem cells are
multipotent
, meaning they can differentiate into cell types found in their native tissue.

For example,
Hematopoietic (blood-forming) stem cells, found in umbilical cord blood, can become any type of blood cell.

Research is being done to convert multipotent stem cells to pluripotent ones, so they can become very different cell types (for example, a hematopoietic stem cell that becomes a neuron).
Example application of stem cells:
In a very recent study, scientists were able to create lung and airway cells from stem cells for the first time ever.

Used a compound that converts embryonic stem cells or induced pluripotent stem cells into precursors to lung and airway cells, and eventually got functional lung tissue

Scientists hope to be able to improve the quality and quantity of lung transplants, as well as study "model" lungs to gain insight about certain diseases.

Bioprinting using stem cells to manufacture organs
Tissue engineering...
is "the application of principles and methods of engineering
and life sciences toward fundamental understanding of
structure-function relationship in normal and pathological
mammalian tissues and the development of biological
substitutes to restore, maintain, or improve tissue function."

Currently there are only 5 tissues approved for use
Cardiac regeneration:
Aims to create new, functioning tissue to replace old tissue that is no longer working, or to be used in the study of diseases to cardiac tissue.

Required:
selection of a human cell source,
establishment of cardiac tissue matrix, electromechanical cell coupling,
robust and stable contractile function, and functional vascularization
Challenges of cardiac reengineering:
Cartilage engineering:
There are several different approaches to the engineering of cartilage tissue:
Using natural and synthetic biomaterial scaffolds
Allogenic and autologous sources of mature chondrocytes
Chondroinductive growth factors
What's to come...
The future of tissue engineering is bright.

Over 70 companies are spending $600 billion
annually
in research to develop new ways to engineer tissue.
There are several ways that animals can be used to help in the growing or regenerating of organs.
Xenotransplantation
is the transplant of tissues, organs, or other living cells from one species to another.
Growing organs on animals
WHAT?
HOW?
WHY?
To date, many pig skin and pig
valve transplants have
been done successfully for
patients in need, but
not full organs.
Now, research is changing that.
There is a huge shortage of donor organs.

Last year, over 6500 people died waiting for an organ, and that number is only growing.

Scientists see promise in growing organs in and on animals, and then transplanting those organs into patients who need them.
Scientists are able to take the cells from a particular human organ and transplant them into an animal.

This process is very complex, and will be discussed further shortly...
Xenotransplant
Japan is the leader in xenotransplant––transplanting cells, tissues, organs from one species to another.

Scientists have a plan to “introduce a human stem cell into the embryo of an animal to create what is termed a “chimeric embryo” that can be implanted into an animal’s womb”.

They say this will then grow the perfect human organ (ex. kidney or heart) as the animal matures.
Then will slaughter the animal to harvest the organ.
Japanese scientists were recently approved to begin eperimenting with human organs in animals.
Stem cells are already used to repair/replace
body parts, and they have very low risk of rejection.

Japanese scientists now will begin experimenting
with human organs.
They will attempt to grow human organs inside
the womb of a pig via cultured stem cells.
The organ grows inside the animal and
is removed by slaughter.
There are pros and cons to
the emerging field of xenotransplantation:
Pros:
Increased quantity of donor organs
More transplants = more lives saved
Low risk of cross-species disease from pigs due to phylogenetic distance from humans
Cons:
Past issues with xenotransplant rejection
Scientists believe, however, that newly modified pigs will be more compatiable
Risk of new infection
REGENERATIVE
MEDICINE

IN SUMMARY...
Regenerative medicine is a developing scientific field that is expected to grow significantly in the near future, with the promise of improving quality of life for many.

Stem cells are the foundation and core of regenerative medicine because of their capacity to become such a wide variety of cell types.

New and continuing research in the fields of tissue engineering and xenotransplantation could redefine the way we think about organ transplants and repair.
Bibliography:
http://www.technologyreview.com/news/406651/pig-to-human-transplants-on-the-horizon/
http://www.telegraph.co.uk/science/science-news/10132347/Human-organs-could-be-grown-in-animals-within-a-year.html
http://theweek.com/article/index/246171/human-organs-grown-in-pigs
http://www.nature.com/nbt/journal/v18/n10s/full/nbt1000_IT53.html
http://bobsnewheart.wordpress.com/2012/08/24/human-organs-from-pigs-but-youd-have-to-kill-one-to-get-one/
http://www.advancedcell.com/patients/regenerative-medicine/
http://www.crm.ed.ac.uk/about/what-regenerative-medicine
http://www.cbs.asu.edu/sites/default/files/people/.../Maienschein_RegenMed.pdf‎
http://www.sciencedaily.com/releases/2013/12/131201140209.htm
http://www.nature.com/nature/journal/v444/n7118/full/nature05142.html
http://www.organogenesis.com/science/regenerative-medicine/
http://www.cirm.ca.gov/our-funding/regenerative-medicine-consortium
http://www.nature.com/nature/journal/v503/n7475_supp/full/503S7a.html
http://www.mirm.pitt.edu
http://www.wakehealth.edu/WFIRM/
Selecting the right number of human cells
Adult and embryonic stem cells have been sucessful
Some cells are easer to get than others
Establishing a cardiac-like tissue matrix
Scaffolds of biomaterial are used to train the cells how to grow
Construct size and need for vascularization
Not an issue if oxygen is properly controlled––not too much, not enough
Electromechanical function
Most cells learn impulses from host cells, some get confused
Advanced culture platforms / Imaging
Difficult to figure out how to design and record how tissue is constructed
Full transcript