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Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures
- 10-15 years from now: cell infusion centers
- Allogenic cells with no immunosuppressive drugs
- MSC field – rapidly expanding
- MSC trials – Allo vs. Auto
- Mesenchymal stem cells: immune evasive
- Translational timeline for MSC
- Rapid increase in MSC clinical trials
- Still no major clinical successes
- Drug discovery model and MSC
- Systemic infusion is used in >50% of trials
- Trials involving systemic infusion have failed
- Reason for challenges/failures
- Culture expanded MSCs don't roll on endothelium
- Homing surface molecules on culture MSC
- Limited efficiency of MSCs for homing
- Chemically attaching homing ligands on cells
- Single cell resolution
- Model to assess homing
- Increased homing of SLeX -MSCs
- Lack of control over MSCs post transplantation
- Fate of transplanted cells
- Control over each implanted cell
- Controlling cells and their microenvironment
- Particles internalized by cells - imaging
- Particle engineered cells & immuno-suppression
- What increases IDO expression
- Donor variability leads to functional variability
- IDO expression + improved immuno-suppression
- Same approach in Beta-cells, & Macrophages
- Towards improved imaging of transplanted MSCs
- Using MSC for targeted delivery of biologics
- mRNA transfection
- Triple transfected hMSCs
- Modification leads to rolling response - video
- IL-10 present only in triple transfected
- ‘Functional benefit’
- Need to get MSC to destination fast
- Developing tools to monitor the environment
- Monitoring quench sensor signal via microneedle
- Spatial-temporal imaging of a single MSC
- Sensing of secretion from neighboring cells
- Potential for sensing cell niches in living animals
- Bioengineered approaches - summary
- Deterministic cell rolling
- Cell adhesion cytometry
- Acknowledgements
- Funding
Topics Covered
- MSCs from discovery to over 450 clinical trials
- Current challenges to maximize clinical success
- Technologies for controlling cell fate and function following transplantation
- mRNA transfection strategy using cells for targeted delivery of biologics
- Engineering cells with an intracellular depots of phenotype altering agents
- Drug delivery or programming cell fate via intracrine-, paracrine-, and endocrine-like mechanisms
- Next generation nanonsensors to study secretome in vivo
Talk Citation
Karp, J. (2021, October 11). Nanoengineering the cell surface for targeted drug and cell delivery [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/GWOH9017.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Jeff Karp, Consultant: Gecko Biomedical, Skintifique Grant/Research Support (Principal Investigator): Sanofi Stock Shareholder (Self-managed): Gecko Biomedical, Skintifique
Nanoengineering the cell surface for targeted drug and cell delivery
Other Talks in the Series: Nanomedicine
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is Jeff Karp.
I'm associate professor at the
Brigham and Women's Hospital,
Harvard Medical School,
also affiliate faculty
at MIT through the Health
Sciences and Technology program,
and a principal faculty at the
Harvard Stem Cell Institute.
And today, I'm going to
be describing for you some
of the technologies that we've
been developing in my laboratory
that aim to use
nanomedicine to control
cells following transplantation.
So this is directly applicable
to cell-based therapy.
0:36
I have a few disclosures
to get out of the way.
I consult for a number of companies.
And this is an
institutional requirement
that I make these disclosures
in all of my presentations.
I also own equity in Gecko
Biomedical and in Skintifique.
0:55
Ten to 15 years from now, I believe
that you, a colleague, a friend,
a family member, will
visit cell infusion
centers to receive routine therapy
for multiple diseases and tissue
defects.
1:10
And I believe that this is possible
because an allogeneic cell source
has been identified where you
can actually expand those cells,
derive them from one person,
expand them, and then transfer them
into somebody else, administer
them, without any immune-suppressive
regimen.
And these cells were discovered
by Alexander Friedenstein in 1976.
And he observed that these
cells in the bone marrow
could be culture expanded.
And they exhibited
multi-potential properties.
Some years later, they were
coined mesenchymal stem cells
by Arnold Caplan.
And these cells have very
intriguing properties.
In addition to being
culture expanded,
they can promote angiogenesis,
so new blood vessel formation,
and stabilize those blood vessels.
They can also differentiate
into multiple cell
types that can create
connective tissues,
such as bone, fat, and cartilage.
And they also have impressive
immunomodulatory behavior.
So they can actually
downregulate inflammation.