Module 3- Regenerative Medicine: Stem Cells Flashcards
What is the goal of regenerative medicine?
To accelerate the pace at which the body heals itself to a clinically relevant timescale
3 elements of regenerative medicine
Regenerative medicine is the process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function
A history of regeneration
- In their 1937 “The Culture of Organs,” Nobel Laureate Alexis Carrel and American aviator Charles Lindbergh wondered… Could you use a bioreactor to grow full organs?
- A bioreactor is a device that supports a biologically active environment — think of a vessel that hosts organic chemical processes
The coining of ‘regenerative’
- A 1992 article on hospital administration had “Regenerative Medicine” as a bold print title and stated — “A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.”
- From 1995 to 1998, the understanding of stem cells and their applications led to widespread use of the term “Regenerative Medicine”
Consider a newt… what is stopping us from being able to regenerate our organs? (video)
https://www.youtube.com/watch?v=_rtF_coKT8U
The regenerative medicine toolbox
History of stem cells timeline
- The history of stem cells can be traced back to Ancient Greece, when Aristotle observed lizards’ regenerative properties.
- Major breakthroughs emerged after 1961, which bring us to today’s era of stem cell technologies…
The stem cell revolution
The scope of global stem cell clinical trials
As of January 2018, over 5000 stem cell clinical trials have been performed.
What are stem cells?
Foundational cells for every organ and tissue in the body — they replace cells that are injured or lost
What are the 3 key properties of stem cells?
- The ability to self-renew
- They are unspecialized
- The ability to
differentiate
What is cell potency?
A cell’s ability to differentiate into other cell types.
What can totipotent cells give rise to?
The placenta and the embryo
Diagram showing journey of stem cells from multipotent to specialized
What are the 3 types of stem cells?
- Embryonic stem cells
- Adult stem cells
- Induced pluripotent stem cells
Embryonic stem cells diagram
Adult stem cells diagram
Induced pluripotent stem cells diagram
Key info about embryonic stem cells
- Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst — they can renew indefinitely
- ESCs can differentiate into any of the primary germ layers, which include 220 cell types in the body…
● Ectoderm (exoskeleton)
● Mesoderm (develop into organs)
● Endoderm (form inner lining of organs)
… but this can form teratomas (tissues from more than one germ layer)
Diagram showing the different types of specialized cells that ESCs can differentiate into
Mesoderm cells- middle layer
Can be used to treat heart failure, anemia, leukemia, arthritis, bone fracture
Endoderm cells- internal layer
Can be used to treat COPD, diabetes, cirrhosis
Ectoderm cells- external layer
Can be used to treat macular degeneration, Parkinson’s disease, ALS
Map showing different stem cell policies around the globe
Major events in stem cell research policy (1996-2000)
The 1996 Dickey-Wicker Amendment
● Prohibits the use of federal funds towards research involving the creation or destruction of human embryos
The 2000 NIH guidelines for human pluripotent stem cells
- The guidelines stipulate that human ESCs…
● Must be derived with private funds from frozen embryos from fertility clinics
● Must have been created for fertility treatment purposes;
● Must be in excess of the donor’s clinical need
● Must be obtained with consent of the donor.
Major events in stem cell research policy (2001-2016)
President Bush 2001 executive order
● Prohibited federal funding for human embryonic stem cell research
● Only cell lines derived prior to August 2001 could be used
● This did not affect private sector or state funding
In 2009, President Obama reverses the 2001 executive order
● Removed barriers to responsible scientific barriers involving embryonic stem cells
The 2016 21st Century Cures Act
● Assures timely regulatory review of regenerative therapies, including cell therapies enabled by stem cell therapy research.
When did the human embryonic stem cell clinical trial occur? + info about it
2001
- A transplantation of oligodendrocytes derived from human embryonic stem cells into spinal cord injured individuals.
- The study aimed to have 10 participants — was only able to have 4.
- Although there have been no official published results, there have been neither adverse effects nor improvements reported.
Other noteworthy stem cell clinical trails
VitaCyte
VitaCyte is developed through a regiment of adding and removing growth factors at precise developmental timepoints
Therapeutic cloning (somatic cell nuclear transfer)
- Somatic cell nuclear transfer harnesses the potential to use one’s own DNA — the same technique used during reproductive cloning.
- An enucleated egg has one’s genetic material inserted and then it develops into a blastocyst.
Somatic cell nuclear transfer video
https://www.youtube.com/watch?v=bbZiOiPVG6c
Adult stem cells (somatic stem cells)
● Undifferentiated and multiponent cells existing within differentiated tissues
● Can be tissue specific stem and progenitor cells, bone marrow stem cells, adult mesenchymal stem cells, or amniotic fluid and cord blood stem cells
● Can renew themselves a number of times, but not indefinitely
● Ethically uncomplicated
Adult stem cells- Hematopoietic stem cells
● Hematopoietic stem cells (HSCs) give rise to all blood cell types — myeloid lineage and lymphoid lineage
● Need 100 billion new blood cells each day, and HSCs are the only source of this new blood
● Clinically used for blood disorders and types of leukemia
What is the stem cell niche?
The microenvironment and the physical anatomical position where stem cell are found
Autologous Haematopoietic Stem Cell Transplant
AHSCT is an immunosuppressive chemotherapy treatment combined with reinfusion of blood stem cells to rebuild the immune system.
Mesenchymal stem cells
● Mesenchymal stem cells (MSCs) are typically derived from bone marrow stromal cells, although there are several sources.
● Specialized cells of skeletal tissues
● Clinically, important for bone defects, cardiac repair, cartilage repair
MSC clinical trials classified by disease
MSC and Heart Regeneration
MSC and Heart Regeneration video
https://www.youtube.com/watch?v=skchOEzWbn0
Umbilical cord and amniotic stem cells
- Recent studies are beginning to compare the quality of stem cells based on where they are harvested from.
- Are stem cells harvested from younger sources more viable?
Amniotic stem cells
● Mixture of stem cells from amniotic fluid and membrane
● Can differentiate into cells of all three germ layers
Induced pluripotent stem cells (iPSCs)
- iPSCs were identified in 2007 and won the Nobel Prize in 2012.
- They are pluripotent stem cells derived from a non-pluripotent source, typically adult somatic cell, by inducing a forced expression of certain genes.
iPSC diagram
Table showing the stem cells used to treat different diseases
Stem Cell Clinics in the United States
FDA cautions against unapproved stem cell therapies- video
https://www.youtube.com/watch?v=onnlZeQlai0
Safety concerns for unproven stem cell treatments
Administration site reactions
● The ability of cells to move from the placement sites and changing
into inappropriate cell types or multiply
● Failure of the cells to work as expected
● The growth of tumors
In August of 2017, the FDA announced an increased enforcement of regulations and oversight of stem cell clinics — including
administrative actions, judicial and criminal enforcement
Although over 5000 clinical trials the list of FDA approved products is very limited
The only stem cell-based products that are FDA-approved for use in the United States consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood.
