Stem Cells and Plastic Surgery

Dr. Kenneth DickieRoyal 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 cells How are stem cells defined?defined?

Differentiation and Commitment

1) Self-renewal

2) Multi-potential

3) 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.

• 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 beingStudied to learn how to regeneratea patient’s own damaged tissuesand organs, without the possibilityof rejection by the immune system.

NO!

Combining cloning with the use of Combining cloning with the use of embryonic stem cellsembryonic stem cells

Egg Cell

Healthy Adult Cell: nuclear material “matches” the patients; no rejection

Generate humanEmbryonic stem cellswithout using sperm

Spinal cord injured patient

RegenerativeTherapy

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 in:Bone marrow

BrainLiver

PancreasSkin

MuscleIntestine

& other organs

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

MUSCLESTEM

CELLS

NEURAL STEM CELLSMESENCHYMAL

STEM CELLS

FAT

CARTILAGE

MUSCLE

CARDIACAND

SKELETAL

BONE

FIBRO-BLAST

NEURONS

WHOLEMOUSE

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?

Bone Bone marrowmarrow

Adipose Adipose 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: UCLAChris Eagon, Wash U. St Louis

Neo-organoid (new tissue) created from adipose – derived adult stem cells seeded

onto a biodegradable matrix

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)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

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

ControlControl MSC treatedMSC treated

MSCs protect cartilage and boneMSCs 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 ProtectionMeniscal Repair - Cartilage Protection

Complete menisectomyComplete menisectomy Partial menisectomyPartial 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: @RCPSurgeryTwitter Personal: @DrKennethDickie

Google+: plus.google.com/+RoyalcentreofplasticsurgeryinBarrie/

Google+ Personal: plus.google.com/+DrKennethDickieBarrie

or Call Us at 705-726-2800