Module 3- Regenerative Medicine: Stem Cells Flashcards

1
Q

What is the goal of regenerative medicine?

A

To accelerate the pace at which the body heals itself to a clinically relevant timescale

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2
Q

3 elements of regenerative medicine

A

Regenerative medicine is the process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function

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3
Q

A history of regeneration

A
  • 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
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4
Q

The coining of ‘regenerative’

A
  • 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”
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5
Q

Consider a newt… what is stopping us from being able to regenerate our organs? (video)

A

https://www.youtube.com/watch?v=_rtF_coKT8U

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6
Q

The regenerative medicine toolbox

A
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7
Q

History of stem cells timeline

A
  • 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…
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8
Q

The stem cell revolution

A
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9
Q

The scope of global stem cell clinical trials

A

As of January 2018, over 5000 stem cell clinical trials have been performed.

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10
Q

What are stem cells?

A

Foundational cells for every organ and tissue in the body — they replace cells that are injured or lost

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11
Q

What are the 3 key properties of stem cells?

A
  1. The ability to self-renew
  2. They are unspecialized
  3. The ability to
    differentiate
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12
Q

What is cell potency?

A

A cell’s ability to differentiate into other cell types.

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13
Q

What can totipotent cells give rise to?

A

The placenta and the embryo

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14
Q

Diagram showing journey of stem cells from multipotent to specialized

A
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15
Q

What are the 3 types of stem cells?

A
  • Embryonic stem cells
  • Adult stem cells
  • Induced pluripotent stem cells
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16
Q

Embryonic stem cells diagram

A
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17
Q

Adult stem cells diagram

A
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18
Q

Induced pluripotent stem cells diagram

A
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19
Q

Key info about embryonic stem cells

A
  • 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)

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20
Q

Diagram showing the different types of specialized cells that ESCs can differentiate into

A
21
Q

Mesoderm cells- middle layer

A

Can be used to treat heart failure, anemia, leukemia, arthritis, bone fracture

22
Q

Endoderm cells- internal layer

A

Can be used to treat COPD, diabetes, cirrhosis

23
Q

Ectoderm cells- external layer

A

Can be used to treat macular degeneration, Parkinson’s disease, ALS

24
Q

Map showing different stem cell policies around the globe

A
25
Q

Major events in stem cell research policy (1996-2000)

A

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.

26
Q

Major events in stem cell research policy (2001-2016)

A

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.

27
Q

When did the human embryonic stem cell clinical trial occur? + info about it

A

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.
28
Q

Other noteworthy stem cell clinical trails

A
29
Q

VitaCyte

A

VitaCyte is developed through a regiment of adding and removing growth factors at precise developmental timepoints

30
Q

Therapeutic cloning (somatic cell nuclear transfer)

A
  • 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.
31
Q

Somatic cell nuclear transfer video

A

https://www.youtube.com/watch?v=bbZiOiPVG6c

32
Q

Adult stem cells (somatic stem cells)

A

● 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

33
Q

Adult stem cells- Hematopoietic stem cells

A

● 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

34
Q

What is the stem cell niche?

A

The microenvironment and the physical anatomical position where stem cell are found

35
Q

Autologous Haematopoietic Stem Cell Transplant

A

AHSCT is an immunosuppressive chemotherapy treatment combined with reinfusion of blood stem cells to rebuild the immune system.

36
Q

Mesenchymal stem cells

A

● 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

37
Q

MSC clinical trials classified by disease

A
38
Q

MSC and Heart Regeneration

A
39
Q

MSC and Heart Regeneration video

A

https://www.youtube.com/watch?v=skchOEzWbn0

40
Q

Umbilical cord and amniotic stem cells

A
  • 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?
41
Q

Amniotic stem cells

A

● Mixture of stem cells from amniotic fluid and membrane
● Can differentiate into cells of all three germ layers

42
Q

Induced pluripotent stem cells (iPSCs)

A
  • 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.
43
Q

iPSC diagram

A
44
Q

Table showing the stem cells used to treat different diseases

A
45
Q

Stem Cell Clinics in the United States

A
46
Q

FDA cautions against unapproved stem cell therapies- video

A

https://www.youtube.com/watch?v=onnlZeQlai0

47
Q

Safety concerns for unproven stem cell treatments

A

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

48
Q

Although over 5000 clinical trials the list of FDA approved products is very limited

A

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.