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Stem Cells and Plastic Surgery
Dr. Kenneth Dickie
Royal Centre of Plastic Surgery
Stem cell Plasticity and Cloning
Why are these topics suddenly so prevalent?
What are key issues relating to stem cell use in
Medicine
Mature
Tissues
Stem Cell
How are stem cellsHow are stem cells
defined?defined?
Differentiation and Commitment
1) Self-renewal
Multi-potential
Highly proliferative
Key Issues:
• There are many different types of stem cells-an important
distinction: Embryonic vs. Adult
• Embryonic stem cells are derived from an egg shortly after it
begins to grow, and are totipotent-able to generate any tissue
in the body
• Adult stem cells are found in many different tissues in the
body, and appear to have more restricted and specialized
functions
Key Issues:
• New research in the field of “stem cell plasticity” has
suggested that adult stem cells may have greater
regenerative potential than was previously suspected
Embryonic
stem cells:
Isolated from
human tissue
(1998)
Derivation of Embryonic Stem Cells
Totipotent ES Cells
The generation of federally approved human ES cell lines was all done in
test tubes from eggs collected from human donors, salvaged from cryobanks.
The National Bioethics Advisory Commission recommended only
using human ova left over from in vitro fertilization procedures.
It was from these otherwise discarded cells that the 64 human ES
cell lines were generated which were ultimately approved by the
Bush Administration.
From these lines, only 8 are dividing continually and are available
for use in the investigation into their potential to be used in
regenerative medicine
(not currently studied at Wash U).
It is not known yet if they will be better, be able to repair more
tissues, or live longer than stem cells from adult sources. More
comparisons are needed.
• Federally approved stem cell lines are derived from discarded eggs from
fertility clinics.
Will human cloning be used to create new people?Will human cloning be used to create new people?
Cloning human stem cells
is being
Studied to learn how to
regenerate
a patient’s own damaged
NO!
Combining cloning with the use ofCombining cloning with the use of
embryonic stem cellsembryonic stem cells
Egg Cell
Healthy Adult Cell: nuclear material
“matches” the patients; no rejection
Generate human
Embryonic stem cells
without using sperm
Spinal cord
injured
patient
Regenerative
Therapy
Nuclear transfer is done with a finely drawn glass pipette. Nuclei are shown
in the pipette, ready to be injected into the recipient egg.
Do we have to interfere with human development?
Stem cells also exist in many adult tissues
Embryonic Stem cells
Adult Stem Cells found i
Bone marro
Bra
Liv
Pancre
Sk
Musc
Intesti
&
other orga
Embryonic stem
cells: Isolated
from human
eggs after in
vitro
fertilization OR
donation of
nuclear material
from an already
differentiated
adult cell
(cloning)
Characteristics of Adult Stem Cells
• Found in discreet anatomical sites in many major
organ systems
• Typically, restricted in potential to the organ of
residence (i.e. brain stem cells only make brain
tissue, marrow stem cells make blood, etc.)
• In many cases, most readily evident as a reservoir
of tissue for repair functions.
• Some studies have SUGGESTED that adult stem
cells may be able to contribute to the repair of
liver, brain, muscle, and other tissues.
Adult stem cells exist for many different human organs - can
they serve as an alternative to embryonic stem cells?
Current use of adult stem cells:
• Bone marrow transplantation
Potential uses of adult stem cells:
• Brain and spinal cord injury and disease.
• Repair of heart tissue.
• Regeneration of liver tissue.
• Diabetes therapy - pancreas repair.
• Repair of muscle, blood vessels, and skin
(potential therapies for burn victims)
• And many other possibilities……..
HSCBLOOD
VASCULAR STEM CELLS
HEPATIC STEM CELLS
MUSCLE
STEM
CELLS
NEURAL STEM CELLS
MESENCHYMAL
STEM CELLS
FAT
CARTILAGE
MUSCLE
CARDIAC
AND
SKELETAL
BONE
FIBRO-
BLAST
NEURONS
WHOLE
MOUSE
LIVER
?
?
MESENCHYMAL
STEM CELLS
FAT
CARTILAGE
MUSCLE
CARDIAC
AND
SKELETAL
BONE
FIBRO-
BLAST
NEURONS
??
??
Phenotype of the most primitive MSC populations?Phenotype of the most primitive MSC populations?
Trafficking properties in vivo? In response to injury?Trafficking properties in vivo? In response to injury?
BoneBone
marrowmarrow
AdiposeAdipose
TissueTissue
Adipose-derived
mesenchymal stem
cell (AMSC)
Fat
Bone Cartilage
Muscle
Generation of Adipose-derived MSC (AMSC)
Isolation procedure:
• Take a bucket to the OR; collect fat excised during
liposuction (LA) or gastric bypass (St Louis)
• Dissect away visible vessels and mince
• Collagenase digest and separate by density centrifugation
• +/- HSC removal
• Defined initially by plastic adherence and rapid growth in
minimal mediuum
• Easily transduced and very proliferative
• Collaborators: De Ugarte and Hedrick: UCLA
Chris Eagon, Wash U. St Louis
Neo-organoid (new tissue) created from
adipose – derived adult stem cells seeded
onto a biodegradable matrix
• The tissue was created by
implanting human AMSC on the
matrix into a laboratory strain of
mice that have no immune system.
It is the size of a dime.
• Matrix is very well tolerated, non-
immunogenic, and permissive for
neo-vascularization and systemic
protein delivery.
• These organoids are currently
being used to deliver therapeutic
drugs and proteins such as clotting
factors needed in hemophiliacs,
and their potential to form specific
tissues such as a new pancreas for
diabetic patients.
Adipose Derived Stem Cells
• Recent research has shown that stem cells from fat
have the ability to regenerate nerve tissue, strengthen
damaged heart tissue, heal intestinal fistulas in
Crohn’s Disease, and may be able to be used as a
building block to cosmetically enhance the female
breast.
Adipose derived stem cells
• Clinical evidence that traumatic scars can be eliminated
following stem cell grafting into the scarred region
• If cutaneous scars can be recognized, and eliminated by
stem cells, the same should be true for cutaneous tumors
such as Basal Cell carcinoma, Squamous Cell carcinoma,
and Malignant Melanoma.
There are more urgent needs for stem cells:
Stem Cells and Autogenous Skin Grafts
Skin Grafting of Burn Wounds
Post burn mortality and morbidity:
What if fat from every burn patient could be immediately
harvested at the time of admission, and sent to the tissue lab
for isolation and growth of the patients stem cells.
Under the appropriate chemical stimulation, autogenous skin
would be available for skin grafting by the time the patients
burns have been stabilized.
Post Burn Mortality and Morbidity:
• Cord blood banked stem cells due not possess immune
competence, thus , tissue banks could continue to grow, and
store tissues of varying types (bone, cartilage, fascia, tendon,
skin) which would be immediately available for treatment of
deformities which are either post traumatic, or post tumor
resection-where immediate reconstruction is mandatory.
Bone Regeneration: Mesenchymal stem cells (MSC)
MSCs repair large gaps in
bones in 32 weeks
No evidence of immune
rejection following implantation
of MSC from an unrelated
donor
Phase 2 clinical trials for
large cranio-facial and long
bone defects began in 2002
in Europe and US
Phase 2 clinical trials for
large cranio-facial and long
bone defects began in 2002
in Europe and US
Control MSC treated
MSCs protect cartilage and bone
Phase 1 clinical trial
began in 2002 in
Europe and US
Phase 1 clinical trial
began in 2002 in
Europe and US
Meniscal Repair - Cartilage Protection
Complete menisectomy Partial menisectomy
goat model
•Experimental data suggests that
adipose derived stem cells have the
ability to lodge in a variety of tissue
types following a variety of routes of
administration
•In models of acute local injury ,
these cells appear to preferentially
home to, or accumulate in, the
damaged tissue
•The mechanism of recruitment of
adult stem cells to sites of injury or
disease is a cell-mediated response
What is the Physicians responsibility?
• When medical breakthroughs have the potential to improve
the mental, social or physical wellbeing of our patients, we as
physicians , should exert our influence and knowledge such
that these breakthroughs do not linger in “no mans land”
while the politics are still being debated.
If you have any questions, feel free to contact Dr.
Kenneth Dickie at royalcentreofplasticsurgery.com
 
Stay In Touch
Twitter: @RCPSurgery
Twitter Personal: @DrKennethDickie
Google+: plus.google.com/
+RoyalcentreofplasticsurgeryinBarrie/
Google+ Personal: plus.google.com/
+DrKennethDickieBarrie
or Call Us at 705-726-2800

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Stem Cells and Plastic Surgery

  • 1. Stem Cells and Plastic Surgery Dr. Kenneth Dickie Royal Centre of Plastic Surgery
  • 2. Stem cell Plasticity and Cloning Why are these topics suddenly so prevalent? What are key issues relating to stem cell use in Medicine
  • 3. Mature Tissues Stem Cell How are stem cellsHow are stem cells defined?defined? Differentiation and Commitment 1) Self-renewal Multi-potential Highly proliferative
  • 4. Key Issues: • There are many different types of stem cells-an important distinction: Embryonic vs. Adult • Embryonic stem cells are derived from an egg shortly after it begins to grow, and are totipotent-able to generate any tissue in the body • Adult stem cells are found in many different tissues in the body, and appear to have more restricted and specialized functions
  • 5. Key Issues: • New research in the field of “stem cell plasticity” has suggested that adult stem cells may have greater regenerative potential than was previously suspected
  • 7. Derivation of Embryonic Stem Cells Totipotent ES Cells The generation of federally approved human ES cell lines was all done in test tubes from eggs collected from human donors, salvaged from cryobanks.
  • 8. The National Bioethics Advisory Commission recommended only using human ova left over from in vitro fertilization procedures. It was from these otherwise discarded cells that the 64 human ES cell lines were generated which were ultimately approved by the Bush Administration. From these lines, only 8 are dividing continually and are available for use in the investigation into their potential to be used in regenerative medicine (not currently studied at Wash U). It is not known yet if they will be better, be able to repair more tissues, or live longer than stem cells from adult sources. More comparisons are needed.
  • 9. • Federally approved stem cell lines are derived from discarded eggs from fertility clinics.
  • 10. Will human cloning be used to create new people?Will human cloning be used to create new people? Cloning human stem cells is being Studied to learn how to regenerate a patient’s own damaged NO!
  • 11. Combining cloning with the use ofCombining cloning with the use of embryonic stem cellsembryonic stem cells Egg Cell Healthy Adult Cell: nuclear material “matches” the patients; no rejection Generate human Embryonic stem cells without using sperm Spinal cord injured patient Regenerative Therapy
  • 12. Nuclear transfer is done with a finely drawn glass pipette. Nuclei are shown in the pipette, ready to be injected into the recipient egg.
  • 13.
  • 14. Do we have to interfere with human development? Stem cells also exist in many adult tissues Embryonic Stem cells
  • 15. Adult Stem Cells found i Bone marro Bra Liv Pancre Sk Musc Intesti & other orga Embryonic stem cells: Isolated from human eggs after in vitro fertilization OR donation of nuclear material from an already differentiated adult cell (cloning)
  • 16. Characteristics of Adult Stem Cells • Found in discreet anatomical sites in many major organ systems • Typically, restricted in potential to the organ of residence (i.e. brain stem cells only make brain tissue, marrow stem cells make blood, etc.) • In many cases, most readily evident as a reservoir of tissue for repair functions. • Some studies have SUGGESTED that adult stem cells may be able to contribute to the repair of liver, brain, muscle, and other tissues.
  • 17. Adult stem cells exist for many different human organs - can they serve as an alternative to embryonic stem cells? Current use of adult stem cells: • Bone marrow transplantation Potential uses of adult stem cells: • Brain and spinal cord injury and disease. • Repair of heart tissue. • Regeneration of liver tissue. • Diabetes therapy - pancreas repair. • Repair of muscle, blood vessels, and skin (potential therapies for burn victims) • And many other possibilities……..
  • 18. HSCBLOOD VASCULAR STEM CELLS HEPATIC STEM CELLS MUSCLE STEM CELLS NEURAL STEM CELLS MESENCHYMAL STEM CELLS FAT CARTILAGE MUSCLE CARDIAC AND SKELETAL BONE FIBRO- BLAST NEURONS WHOLE MOUSE LIVER ? ?
  • 19. MESENCHYMAL STEM CELLS FAT CARTILAGE MUSCLE CARDIAC AND SKELETAL BONE FIBRO- BLAST NEURONS ?? ?? Phenotype of the most primitive MSC populations?Phenotype of the most primitive MSC populations? Trafficking properties in vivo? In response to injury?Trafficking properties in vivo? In response to injury? BoneBone marrowmarrow AdiposeAdipose TissueTissue
  • 21. Generation of Adipose-derived MSC (AMSC) Isolation procedure: • Take a bucket to the OR; collect fat excised during liposuction (LA) or gastric bypass (St Louis) • Dissect away visible vessels and mince • Collagenase digest and separate by density centrifugation • +/- HSC removal • Defined initially by plastic adherence and rapid growth in minimal mediuum • Easily transduced and very proliferative • Collaborators: De Ugarte and Hedrick: UCLA Chris Eagon, Wash U. St Louis
  • 22. Neo-organoid (new tissue) created from adipose – derived adult stem cells seeded onto a biodegradable matrix • The tissue was created by implanting human AMSC on the matrix into a laboratory strain of mice that have no immune system. It is the size of a dime. • Matrix is very well tolerated, non- immunogenic, and permissive for neo-vascularization and systemic protein delivery. • These organoids are currently being used to deliver therapeutic drugs and proteins such as clotting factors needed in hemophiliacs, and their potential to form specific tissues such as a new pancreas for diabetic patients.
  • 23.
  • 24. Adipose Derived Stem Cells • Recent research has shown that stem cells from fat have the ability to regenerate nerve tissue, strengthen damaged heart tissue, heal intestinal fistulas in Crohn’s Disease, and may be able to be used as a building block to cosmetically enhance the female breast.
  • 25. Adipose derived stem cells • Clinical evidence that traumatic scars can be eliminated following stem cell grafting into the scarred region • If cutaneous scars can be recognized, and eliminated by stem cells, the same should be true for cutaneous tumors such as Basal Cell carcinoma, Squamous Cell carcinoma, and Malignant Melanoma.
  • 26. There are more urgent needs for stem cells:
  • 27. Stem Cells and Autogenous Skin Grafts
  • 28. Skin Grafting of Burn Wounds
  • 29. Post burn mortality and morbidity: What if fat from every burn patient could be immediately harvested at the time of admission, and sent to the tissue lab for isolation and growth of the patients stem cells. Under the appropriate chemical stimulation, autogenous skin would be available for skin grafting by the time the patients burns have been stabilized.
  • 30. Post Burn Mortality and Morbidity: • Cord blood banked stem cells due not possess immune competence, thus , tissue banks could continue to grow, and store tissues of varying types (bone, cartilage, fascia, tendon, skin) which would be immediately available for treatment of deformities which are either post traumatic, or post tumor resection-where immediate reconstruction is mandatory.
  • 31. Bone Regeneration: Mesenchymal stem cells (MSC) MSCs repair large gaps in bones in 32 weeks No evidence of immune rejection following implantation of MSC from an unrelated donor Phase 2 clinical trials for large cranio-facial and long bone defects began in 2002 in Europe and US Phase 2 clinical trials for large cranio-facial and long bone defects began in 2002 in Europe and US
  • 32. Control MSC treated MSCs protect cartilage and bone Phase 1 clinical trial began in 2002 in Europe and US Phase 1 clinical trial began in 2002 in Europe and US Meniscal Repair - Cartilage Protection Complete menisectomy Partial menisectomy goat model
  • 33. •Experimental data suggests that adipose derived stem cells have the ability to lodge in a variety of tissue types following a variety of routes of administration •In models of acute local injury , these cells appear to preferentially home to, or accumulate in, the damaged tissue •The mechanism of recruitment of adult stem cells to sites of injury or disease is a cell-mediated response
  • 34. What is the Physicians responsibility? • When medical breakthroughs have the potential to improve the mental, social or physical wellbeing of our patients, we as physicians , should exert our influence and knowledge such that these breakthroughs do not linger in “no mans land” while the politics are still being debated.
  • 35. If you have any questions, feel free to contact Dr. Kenneth Dickie at royalcentreofplasticsurgery.com   Stay In Touch Twitter: @RCPSurgery Twitter Personal: @DrKennethDickie Google+: plus.google.com/ +RoyalcentreofplasticsurgeryinBarrie/ Google+ Personal: plus.google.com/ +DrKennethDickieBarrie or Call Us at 705-726-2800

Notas del editor

  1. Our laboratory has characterized a population of cells derived from fat, which have the capacity to differentiate along the adipogenic, osteogenic, chondrogenic, neurogenic, and myogenic lineages.