Welcome to Dr. Kate Brilakis' Learning Portal

how is the
structure and function
of a cell intertwined? 

<- tightly wound DNA = genes less accessible

loosely wound DNA ->
= genes more accessible

1. a single fertilizedegg (zygote)
​ develops into a complex organism with many diverse cell types. 

2. throughout the lifespan of an organism, tissues are maintained and repaired via differentation

 stem cell research is working to...

so we're good?? not so fast...

when do cells differentiate?

so approx. 650,000 embryos transferred resulting in 75,023 live births...
what happened to the other  500,000 embryos last year?  

2023: a Peking University team took cells from three people with type 1 diabetes and reverted them to iPSCs using them to create
clusters of insulin-producing islets.
 1.5 million islets were transplanted in less than 30 min. she has been
 producing enough insulin on her own for over a year now.

enhance drug development
test the safety and effectiveness of new drugs on specific tissues and organs before they are used in humans

understand development and aging
 how tissues and organs form, how aging affects their function, and how these processes relate to disease. 

treat blood disorders and cancers:
 currently used in treatments like bone marrow transplants
for conditions like leukemia. 

illustrate disease modeling
create disease-specific stem cells to study how diseases develop and to test potential therapies 

whoa...that was heavy.

what about the other types of stem cells...

as you determine the future of stem cell research by whom you chose to elect with your votes, perhaps consider this ethical inconsistency...

next time...gene therapy using

CRISPR

what is the potential for stem cell research

how do cells differentiate?

so...

let's talk about stem cell types
​1. totipotent   2. pluripotent   3. multipotent

 stem cells are exposed to chemical or physical signals that cause cellular differentiation such as...

In a 2020 study, researchers reprogrammed a Parkinson’s patient’s skin cells into iPSCs and differentiated them into dopaminergic neurons lost by the disease.

These replacement neurons were transplanted into the brain of the patient and after two years, were shown to be alive and functioning appropriately. The patient has begun to regain some daily function, prompting further investigation into this technique as a Parkinson’s treatment.

the inner cell mass of the blastocyst is removed and cultured 

Project 2025 has emboldened members of Congress to advocate for policies that ban federal funding for embryonic stem cell research. They demand the end of research using what they call "aborted fetal cell lines". This description is misleading.
​If restrictions on federal funding for embryonic stem cell research are adopted, it could significantly impact the resources available for specific areas of cell therapy research and development. in addition, workforce cuts aligned with Project 2025's goals raises concerns about the potential impact on cell therapy development.

it's the process by which a less specialized cell becomes a more specialized cell type by changing the cell's in gene expression. this causes the cell to exhibit distinct structures and functions. 

Stem Cells

in 2020:
there were 326,468* ART cycles performed at 449 reporting clinics in the US.
75,023 live births resulted.
123,304 were embryo banking cycles.
the use of ART has more than doubled over the past decade. Approximately 2.0% of all infants born in the United States every year are conceived using ART. ​https://www.cdc.gov/art/artdata/index.html

transcription factors can essentially turn genes on or off.
​ the mechanism by which transcription factors regulate stem cell fate involves a combination of direct DNA binding and interaction with other cellular machinery like epigenetic modifiers. this network controls the expression of target genes AND gene accessibility.

this is a blastocyst...
​i
t is the source of ESCs used in research

epigenetic regulation includes external/environmental modifications to the DNA. these modifications alter how tightly DNA is wound to packaging proteins which affects the accessibility of transcription factors to their target DNA sequences. 

Pluripotent stem cells can give rise to all of the cell types that make up the body; stem cells derived from the inner cell mass of a blastula are considered pluripotent.

enhance regenerative medicine
​by regenerating and repairing diseased/damaged tissues including spinal cord injuries, diabetes, Parkinson's disease, ALS, Alzheimer's disease,
heart disease, stroke, burns, cancer and arthritis. Harnessing the potential for stem cells
to grow into new tissues provides options for tissue/organ transplants.

where do research labs get these "embryos"...blastocysts?

icm ->

 perinatal stem cells
researchers have discovered multipotent stem cells in amniotic fluid as well as umbilical cord blood. Concerns include
quality assurance, ethical considerations, potential for disease transmission, and the need for improved cryopreservation and biobanking techniques.

 when I googled the word embryo,
this pic is what first popped up

During differentiation, certain genes are activated while others are silenced, leading to the production of specific proteins that determine the cell's structure and function. 

In a small Mayo Clinic study, over half of patients with non-penetrating spinal cord injuries observed improved motor function within weeks of receiving an injection of stem cells derived from their bone marrow. This raises confidence in a clinical application of stem cells to treat spinal cord injuries, with clinical trials also exploring this possibility.

cell to cell interactions:
stem cell and neighboring cells interact directly or by releasing signaling molecules that can cause cells to release factors that influence the behavior of nearby cells. this signaling guides differentiation.

In patients with the “dry” form of age-related macular degeneration (AMD), clinical trials are currently underway to evaluate if transplanting retinal pigment epithelial (RPE) cells derived from iPSCs to replace those lost due to AMD can prevent further vision loss. In animal models, this therapy was shown to prevent blindness.

 “It is important to be clear about the embryo from which stem cells are extracted. It is not implanted and growing in a woman’s uterus. It is not a fetus. It has no recognizable human features or form. It is, rather, a blastocyst, a cluster of cells, growing in a petri dish, barely visible to the naked eye.”  Harvard University Stem Cell Institute

let's look at ESCs first...

Totipotentstem cells can form all the cell types in a body, plus the cells that make the placenta. only cells that result from the first couple of cell divisions after fertilization are totipotent.

and stem cell classifications based on origin...

why does this matter??

 there isn't an 
  Ethical Consistency
between the unregulated use of embryos for IVF and the societal outrage when
discarded IVF embryos are used
to further medical research 

how do scientists recreate embryonic development in the lab?
 stem cells are exposed to chemical or physical signals that cause cellular differentiation 
including:

ultimately gene expression = protein synthesis:
signals ultimately affect gene expression. specific genes are activated or repressed, leading to the production of proteins that determine the cell's fate. 

 stem cell research is working to...

enhance our understanding of the nature of disease by discovering how stem cells mature into heart muscle cells, bone cells, nerve cells etc.

transcription factors
are molecules that regulate which genes are transcribed in a cell.
​they are a critical component to determining the pathway particular stem cells take as they differentiate. divergent transcript factor binding cause a stem cell to differentiate into dramatically different cells.

ok, so let's talk about why these cells show such promise in research and medicine...

 "adult" or somatic stem cells
are ​found in small numbers in tissues like bone marrow and are multipotent meaning they have limited differentiation potential. somatic stem cells can be isolated from tissues and grown in cultures although they are relatively rare and difficult to isolate and culture.

hematopoetic stem cells were harvested from bone marrow more than 50 years ago. these blood-forming stem cells have been used in transplants for patients with leukemia and several other diseases for decades. 

     induced pluripotent stem cells
                          = iPSCs

are somatic cells that are altered to exhibit pluripotent characteristics. genetic reprogramming alters the genes in adult cells so they act like embryonic stem cells. researchers can use reprogrammed cells instead of embryonic stem cells which would prevent immune system rejection of the stem cells.
unfortunately, iPSC differentiation requires multiple steps, and each step requires multiple growth factors. the transformation efficiency isn't great = low yield.
in addition, during the reprogramming process, iPSCs can acquire genetic mutations, increasing the risk of cancer if used in therapeutic applications.  iPSCs are not perfect replicas of ESCs and behave differently causing adverse effects therapeutically. 

molecules become activated by surface binding proteins (ligands) such as growth factors or hormones or by intracellular signals that bind to specific receptors on the stem cell surface

Multipotent stem cells can develop into more than one cell type, but are much more limited than pluripotent cells; adult stem cells and cord blood stem cells are considered multipotent.

growth factors and cytokines:
signaling molecules bind to receptors on the stem cell surface which triggers a cascade of signaling events that affect gene expression. different growth factors/combinations of factors will
induce the differentiation of stem cells into different cell lines

another tool, another cure

what is meant by cell differentiation?

physical/mechanical forces:
stem cells can sense and respond to the physical properties of their environment, such as substrate stiffness. stiffer matrices promote
bone-like cell differentiation while softer matrices favoring neuron and fat cell formation by inducing intracellular signals that can affect gene expression and cell behavior