Stem cells
This presentation is the property of its rightful owner.
Sponsored Links
1 / 66

Stem cells Differential gene expression and cell fate Why manipulate stem cells? PowerPoint PPT Presentation


  • 108 Views
  • Uploaded on
  • Presentation posted in: General

Stem cells Differential gene expression and cell fate Why manipulate stem cells? Potential sources of therapeutic cells Concluding thoughts. pluripotent stem cell. pluripotent stem cell. committed cell. pluripotent - having the potential to develop into any cell type of the body.

Download Presentation

Stem cells Differential gene expression and cell fate Why manipulate stem cells?

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Stem cells differential gene expression and cell fate why manipulate stem cells

Stem cells

Differential gene expression and cell fate

Why manipulate stem cells?

Potential sources of therapeutic cells

Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

pluripotent stem cell

pluripotent stem cell

committed cell


Stem cells differential gene expression and cell fate why manipulate stem cells

pluripotent- having the potential to develop into any cell type of the body


Stem cells differential gene expression and cell fate why manipulate stem cells

http://departments.weber.edu/chfam/prenatal/blastocyst.html


Stem cells differential gene expression and cell fate why manipulate stem cells

Stem cells

Differential gene expression and cell fate

Why manipulate stem cells?

Potential sources of therapeutic cells

Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

Genes are made of DNA


Stem cells differential gene expression and cell fate why manipulate stem cells

DNA is within the nucleus of each of our cells.


Stem cells differential gene expression and cell fate why manipulate stem cells

This DNA is identical in each of the cells of our bodies…


Stem cells differential gene expression and cell fate why manipulate stem cells

…even though different cells have very different structures and functions


Stem cells differential gene expression and cell fate why manipulate stem cells

Q: How do cells with identical genetic compositions become so different from one another?


Stem cells differential gene expression and cell fate why manipulate stem cells

A: Different cells express different subsets of their genes.

In neurons, gene A is expressed but not gene B:

In muscle cells, gene B is expressed but not gene A:

Gene A

Gene A

Gene B

Gene B


Stem cells differential gene expression and cell fate why manipulate stem cells

In muscle cells, gene B is expressed because muscle cells have transcription factors that bind to gene B’s promoter.

(muscle cell specific transcription factors)

Gene B

Gene A

(promoter of gene B)


Stem cells differential gene expression and cell fate why manipulate stem cells

In muscle cells, gene B is expressed because muscle cells have transcription factors that bind to gene B’s promoter.

Gene B

Gene A


Stem cells differential gene expression and cell fate why manipulate stem cells

Stem cells

Differential gene expression and cell fate

Why manipulate stem cells?

Potential sources of therapeutic cells

Progress on stem cell therapeutics


Stem cells differential gene expression and cell fate why manipulate stem cells

  • Stem cells

  • Differential gene expression and cell fate

  • Why manipulate stem cells?

  • Potential sources of therapeutic cells

    • Adult stem cells

    • Embryonic stem cells (IVF embryos)

    • Induced pluripotent stem cells

    • Embryonic stem cells (SCNT-derived)

    • Transdifferentiation

  • Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

Bone marrow contains Hematopoetic Stem Cells


Stem cells differential gene expression and cell fate why manipulate stem cells

irradiation


Stem cells differential gene expression and cell fate why manipulate stem cells

(injection with bone marrow)


Stem cells differential gene expression and cell fate why manipulate stem cells

Adult stem cell types that have been tested clinically

Hematopoetic stem cells

Mesenchymal stem cells

Neural stem cellsAdipose stem cells

Lin et al., 2013


Stem cells differential gene expression and cell fate why manipulate stem cells

Most stem cell clinical trials have used adult stem cells

Lin, et al., 2013


Stem cells differential gene expression and cell fate why manipulate stem cells

Adult Stem Cell Therapies

  • no ethical dilemmas

  • autologous (self) donations are possible

  • cells need not be manipulated or grown in culture

  • no risks of teratomas (tumors)

pros

  • few tissues are represented by adult stem cells

  • those tissues that DO have them have very few

  • if not autologous, MUST be tissue type matched

  • evidence of clinical efficacy limited to HSCs

  • cannot be amplified or maintained in culture

cons


Stem cells differential gene expression and cell fate why manipulate stem cells

  • Stem cells

  • Differential gene expression and cell fate

  • Why manipulate stem cells?

  • Potential sources of therapeutic cells

    • Adult stem cells

    • Embryonic stem cells (IVF embryos)

    • Induced pluripotent stem cells

    • Embryonic stem cells (SCNT-derived)

    • Transdifferentiation

  • Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

http://departments.weber.edu/chfam/prenatal/blastocyst.html


Stem cells differential gene expression and cell fate why manipulate stem cells

Animal Models in which hESC-Derived Cells have been Effective

Deb and Sarda, 2008


Stem cells differential gene expression and cell fate why manipulate stem cells

Clinical Trials using hESCs

2009-2011 Geron Corporation hESC-derived oligodendrocyte progenitors for treatment of spinal cord injuries (Daley, 2012)

-in animal models, these cells car repair damaged neurons

-the first hESC clinical study to overcome FDA restrictions

-four patients enrolled

-no publications yet; no reported negative effects, but unclear if treatments were effective


Stem cells differential gene expression and cell fate why manipulate stem cells

Clinical Trials using hESCs, cont.

2009-present Advanced Cell Technology (ACT) hESC-derived retinal pigment epithelial cells are being used to treat macular degeneration (Schwartz,et al. 2012)

-started with 2 patients, both showed vision improvement and no signs of tumors after 4 months

-study is continuing with higher doses of cells and in more patients


Stem cells differential gene expression and cell fate why manipulate stem cells

ESCs from IVF

  • source tissue plentiful

  • cells divide infinitely in culture

  • easily programmable cells

pros

  • immune response problems

  • ethical controversy

  • tumor risks

cons


Stem cells differential gene expression and cell fate why manipulate stem cells

  • Stem cells

  • Differential gene expression and cell fate

  • Why manipulate stem cells?

  • Potential sources of therapeutic cells

    • Adult stem cells

    • Embryonic stem cells (IVF embryos)

    • Induced pluripotent stem cells

    • Embryonic stem cells (SCNT-derived)

    • Transdifferentiation

  • Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

  • Stem cells

  • Differential gene expression and cell fate

  • Why manipulate stem cells?

  • Potential sources of therapeutic cells

    • Adult stem cells

    • Embryonic stem cells (IVF embryos)

    • Induced pluripotent stem cells

      • issues with iPSCs

      • progress with iPSCs

    • Embryonic stem cells (SCNT-derived)

    • Transdifferentiation

  • Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

Takahashi and Yamanaka 2006


Stem cells differential gene expression and cell fate why manipulate stem cells

  • DNA inserted randomly could create problems with endogenous DNA.

  • DNA insertions are inherited by all progeny of manipulated cell.

  • The genes added could cause cells to be more prone to division.


Stem cells differential gene expression and cell fate why manipulate stem cells

New iPSC protocols do NOT require insertion of foreign DNA

  • Exposure of differentiated cells to chemical treatments caused them to become pluripotent (Masuda et al., 2013).

  • Protein transduction of somatic cells can produce iPS cells (Nemes et al., 2013).

  • Mouse lymphocytes were induced to become pluripotent via acid treatment (Obokata et al., 2014).


Stem cells differential gene expression and cell fate why manipulate stem cells

With iPSCs, the pluripotency must be tested

Stadtfield & Hochedlinger 2010


Stem cells differential gene expression and cell fate why manipulate stem cells

  • Stem cells

  • Differential gene expression and cell fate

  • Why manipulate stem cells?

  • Potential sources of therapeutic cells

    • Adult stem cells

    • Embryonic stem cells (IVF embryos)

    • Induced pluripotent stem cells

      • issues with iPSCs

      • progress with iPSCs

    • Embryonic stem cells (SCNT-derived)

    • Transdifferentiation

  • Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

Many cell types have been derived from human iPS cells

  • hepatocytes (Takebe et al., 2014)

  • neurons (Prilutsky et al, 2014)

  • folliculogenic stem cells (Yang et al., 2014)

  • cardiomyocytes (Seki et al., 2014)

  • pancreatic beta cells (Thatava et al, 2011)


First ipsc clinical trial to begin this year

First iPSC clinical trial to begin this year

  • lab of Dr. Masayo Takahashi at Riken in Kobe, Japan

  • 6 patients with macular degeneration in trial

  • iPSCs will be reprogrammed in culture to become retinal pigment epithelium

  • once 50,000 cells per patient are produced, these will be introduced back into the retinas


Stem cells differential gene expression and cell fate why manipulate stem cells

Grskovic, et al. 2011


Successful disease in a dish models

Successful “disease in a dish” models

  • Familial dysautonomia, a genetic disease of autonomic nervous system

  • Rett Syndrome, a disease within the autism spectrum

  • HGPS (progeria), premature aging

  • Parkinson’s, degradation of midbrain dopaminergic neurons leading to loss of motor activity

Grskovic, et al. 2011


Stem cells differential gene expression and cell fate why manipulate stem cells

iSPCs

  • patient-derived pluripotent cells

  • once established, cells divide infinitely in culture

  • easily programmable cells

  • less ethical controversy than ESCs

  • produce excellent tools for studying disease

pros

  • cells require a lot of manipulation to become iSPC

  • evidence of immunogenicity of iPSCs (Fu, 2013)

  • low rate of induced pluripotency (~.2%)

  • tumor risks

cons


Stem cells differential gene expression and cell fate why manipulate stem cells

  • Stem cells

  • Differential gene expression and cell fate

  • Why manipulate stem cells?

  • Potential sources of therapeutic cells

    • Adult stem cells

    • Embryonic stem cells (IVF embryos)

    • Induced pluripotent stem cells

    • Embryonic stem cells (SCNT-derived)

    • Transdifferentiation

  • Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

Freeman, 2012


Stem cells differential gene expression and cell fate why manipulate stem cells

ESCs from SCNT

  • cells divide infinitely

  • easily programmable cells

  • genetically identical to patient

  • great for disease modeling

pros

  • ethical controversy

  • will require oocyte donors

  • not tested much with human cells

cons


Stem cells differential gene expression and cell fate why manipulate stem cells

  • Stem cells

  • Differential gene expression and cell fate

  • Why manipulate stem cells?

  • Potential sources of therapeutic cells

    • Adult stem cells

    • Embryonic stem cells (IVF embryos)

    • Induced pluripotent stem cells

    • Embryonic stem cells (SCNT-derived)

    • Transdifferentiation

  • Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

Transdifferentiation

Graf, 2011


Stem cells differential gene expression and cell fate why manipulate stem cells

Graf, 2011


Stem cells differential gene expression and cell fate why manipulate stem cells

  • Stem cells

  • Differential gene expression and cell fate

  • Why manipulate stem cells?

  • Potential sources of therapeutic cells

    • Adult stem cells

    • Embryonic stem cells (IVF embryos)

    • Induced pluripotent stem cells

    • Embryonic stem cells (SCNT-derived)

    • Transdifferentiation

  • Concluding thoughts


Stem cells differential gene expression and cell fate why manipulate stem cells

ESCs

iPSCs

derivation

cancer risk

immunogenicity

growth in culture

ability to program

embryos

high

high

good

good

somatic cells

very high

some?

good

good


Stem cells differential gene expression and cell fate why manipulate stem cells

ESCs are currently considered the “gold standard” for pluripotency.

Current research is investigating whether iPSCs are truly equivalent to ESCs.

Many scientists developing iPSCs still must use ESCs for comparison in their experiments.


Stem cells differential gene expression and cell fate why manipulate stem cells

Conditions that might be alleviated using stem-cell derived transplantations (a partial list)

macular degeneration

Parkinson’s

Type II Diabetes

Altzheimer’s

heart disease

spinal cord injuries

burns

Huntington’s


Stem cells differential gene expression and cell fate why manipulate stem cells

Challenges to cell culture-derived transplantations

cancer risk from cultured cells

immune response from cultured cells

creating cultured cells to have all the functions of those cells produced by the body

the necessity of producing a LOT of the target cells in culture

creating cultured cells that integrate with host tissues


Stem cells differential gene expression and cell fate why manipulate stem cells

iPSCs are outstanding tools for disease modeling

useful as a way to test drugs without experimenting on patients

a means to generate therapies specific to specific patients

can be used also to study diseased cells and figure out what is wrong with them


  • Login