Module 3- Regenerative Medicine: Stem Cells

Question 1

What is the goal of regenerative medicine?

Answer 1

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

Question 2

3 elements of regenerative medicine

Answer 2

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

Question 3

A history of regeneration

Answer 3

• 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

Question 4

The coining of ‘regenerative’

Answer 4

• 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”

Question 5

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

Answer 5

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

Question 6

The regenerative medicine toolbox

Answer 6

Question 7

History of stem cells timeline

Answer 7

• 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…

Question 8

The stem cell revolution

Answer 8

Question 9

The scope of global stem cell clinical trials

Answer 9

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

Question 10

What are stem cells?

Answer 10

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

Question 11

What are the 3 key properties of stem cells?

Answer 11

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

Question 12

What is cell potency?

Answer 12

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

Question 13

What can totipotent cells give rise to?

Answer 13

The placenta and the embryo

Question 14

Diagram showing journey of stem cells from multipotent to specialized

Answer 14

Question 15

What are the 3 types of stem cells?

Answer 15

• Embryonic stem cells
• Adult stem cells
• Induced pluripotent stem cells

Question 16

Embryonic stem cells diagram

Answer 16

Question 17

Adult stem cells diagram

Answer 17

Question 18

Induced pluripotent stem cells diagram

Answer 18

Question 19

Key info about embryonic stem cells

Answer 19

• 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)

Question 20

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

Answer 20

Question 21

Mesoderm cells- middle layer

Answer 21

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

Question 22

Endoderm cells- internal layer

Answer 22

Can be used to treat COPD, diabetes, cirrhosis

Question 23

Ectoderm cells- external layer

Answer 23

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

Question 24

Map showing different stem cell policies around the globe

Answer 24

Question 25

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

Answer 25

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.

Question 26

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

Answer 26

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.

Question 27

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

Answer 27

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.

Question 28

Other noteworthy stem cell clinical trails

Answer 28

Question 29

VitaCyte

Answer 29

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

Question 30

Therapeutic cloning (somatic cell nuclear transfer)

Answer 30

- 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.

Question 31

Somatic cell nuclear transfer video

Answer 31

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

Question 32

Adult stem cells (somatic stem cells)

Answer 32

● 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

Question 33

Adult stem cells- Hematopoietic stem cells

Answer 33

● 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

Question 34

What is the stem cell niche?

Answer 34

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

Question 35

Autologous Haematopoietic Stem Cell Transplant

Answer 35

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

Question 36

Mesenchymal stem cells

Answer 36

● 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

Question 37

MSC clinical trials classified by disease

Answer 37

Question 38

MSC and Heart Regeneration

Answer 38

Question 39

MSC and Heart Regeneration video

Answer 39

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

Question 40

Umbilical cord and amniotic stem cells

Answer 40

- 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?

Question 41

Amniotic stem cells

Answer 41

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

Question 42

Induced pluripotent stem cells (iPSCs)

Answer 42

- 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.

Question 43

iPSC diagram

Answer 43

Question 44

Table showing the stem cells used to treat different diseases

Answer 44

Question 45

Stem Cell Clinics in the United States

Answer 45

Question 46

FDA cautions against unapproved stem cell therapies- video

Answer 46

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

Question 47

Safety concerns for unproven stem cell treatments

Answer 47

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

Question 48

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

Answer 48

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.