fri halland 345 - baptist health south florida · tendonitis of a variety of tendons (tennis elbow,...

6/22/2016

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Regenerative Medicine

Halland Chen, MD

Speaker Disclosures

I disclose that I am not a consultant or have any

financial interests.

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What is regenerative medicine?

Regeneration of human cells, tissues, or organs to restore or establish normal

function. (Chris Mason, Ph.D.)

Cell therapy is one of the maincomponents of regenerative medicine.

Cell therapy uses cells, such as stem cells, to regenerate diseased tissue in the

human body.

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What are stem cells?

A “master cell” in the body which can multiply indefinitely and create many

different types of cells ( >200 ) in the human body (blood cells, skin cells,

cartilage cells, etc.).

Stem cells help to renew and repair cells in the human body.

Where are stem cells found?

Bone marrow

Fat

Tissues

(heart, liver, kidneys, etc.)

What are stem cell treatments?

Autologous Stem Cell treatments (own cells)

Allogenic Stem Cells (donor cells)

Induced Pluripotent Stem Cells (cells converted to stem cells)

Pharmaceutical treatments (activate stem cells)

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What can stem cells treat in the future?

FDA studies to find future cures

FDA Phase I, II, III Studies

Current FDA Phase III Studies:

Bone marrow transplant rejection Diabetic foot ulcers

Crohn’s Disease Limb Ischemia (blood flow)

Heart attack prevention and treatment Knee cartilage repair

Heart failure Multiple Sclerosis

Cancer treatments (bone marrow cancer) Parkinson’s Disease

Treatments are coming but will take time

Q: What types of stem cell treatments can be done today?

A: Orthopedicstem cell treatments

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The science of stem cell treatments for

orthopedic conditions

Why are stem cells important?

Because they are the body’s repaircells.

They are the onlycells that can renew and regrow.

To repaira laceration, repair occurs by growth of fibroblasts (skin stem cells).

To heala fracture, osteoblasts (bone stem cells) are needed.

After a haircut, hair regrowth is thanks to hair follicle cells (hair stem cells).

Without stem cell you would only live approximately two days!

Classification of stem cells

Who they come from

Allogeneic (non-self) and autologous (self)

Embryonic and Adult

Where they come from

Blood, bone marrow, adipose, and placenta

What they do

Hematopoeticand Mesenchymal

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Embryonic Stem Cells

By far the most controversial stem cells.

Most ESC lines outlawedby President George W. Bush (2000-2008) .

Research reinstated by President Barack Obama.

U.S. government has lifted some bans but FDA has still significantly restricts

ESC use in humans.

Since an embryo (potential living human being) is destroyed creating ESCs,

there are ethical issues.


Initially was to have the most potential for correcting and curing

certain conditions due to their plasticity or ability to morph into

many cell types.

However, patients will inherit any potential diseases that the

embryo may have.


There is a significant potential that the cells can grow unchecked and

essentially act as a tumor.

There are certain immunogenic factors. Will the body attack the stem cells as

being foreign invaders? The patient may be required to take drugs to ward off

cell rejection.

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Autologous Stem Cells

Derived from the patient themselves.

Noproblems with immunity or rejection.

May not be useful for auto-immune or genetic diseases—has patient’s

problems. Type I diabetes, muscular dystrophy

Age-specific changes. Efficacy, numbers


Hematopoietic Stem Cells (HSCs) Commonly found in bone marrow

Mesenchymal Stem Cells (MSCs)Commonly found in fat tissue (adipose)

Induced Pluripotent Stem Cells (iPSCs)

MUSE Cells(Multi-lineage differentiating stress enduring cells)

VSEL (Very Small Embryonic-Like Stem Cells)Thought to be the body's emergency stem cell supply

Hematopoietic Stem Cells

HSCs discovered in 1960’s by Dr. Till and Dr. McCulloch.

Over 50 years of clinical use, mostly in bone marrow transplants for cancer.

Located in redbone marrow (primarily), also para-aortic, fetal liver.

Drive tissue regeneration

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Mesenchymal Stem Cells

In 1987, Dr. Arnie Caplan coined the term “mesenchymal stem cell.”

MSCs were initially thought to be the most important cell because early

technology was only capable of expanding and differentiating MSCs in vitro.

It was initially felt that if sufficiently expanded and then transplanted, MSCs

would produce clinical success.


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Main sources

Adipose tissue (largest source)

Umbilical cord blood

Red marrow (few)

Amniotic fluid

Dental pulp

Hair follicles

The highest MSC density is fat in lower abdomen.(more so in men than women)


Stem cell sources for clinical use

Bone marrow

Fat tissue

Blood

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Bone marrow stem cells

Bone Marrow Aspirate Concentrate (BMAC)

Obtained by centrifugation or with specialized needle.

Most commonly aspirated from hip bone.Cell contents: HSCs > MSCs

Typically remove about 20-60cc of bone marrow.

Fat tissue stem cells

Abundant in MSCs.

Harvested as graft or lipoaspirate.

Adipose tissue can act as biomaterial scaffold.

Adipose tissue components:Adipocytes

Stromal vascular fraction (MSCs)

Connective tissue

Fat tissue stem cells

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Fat tissue stem cells: best collection sites

Men: Abdomen

Women: Biopsy region did not influence cell yield

Ageand Body Mass Index (BMI) of donor did not influence cell yield.

How are fat stem cells processed before use?

Fat graft:

As is, or some washing and rinsing steps.

Lipogems:

Advanced cleansing process.

Bone marrow vs. fat stem cells

These are both valuable sources of stem cells.

However, there are significant differences.

Fat has more MSCs compared to Marrow. Fat has the advantage in this

department.

Fat and marrow have similar numbers of HSCs but those of fat are short lived

and seem to be different from the usual HSCs. Bone marrow has more

effective HSCs and essentially greater numbers. Bone marrow has the

advantage.

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Bone marrow vs. fat stem cells

Blood stem cells and growth factors

Platelet Rich Plasma

Blood cells

6%

94%

0%

PlateletsRed Blood CellsWhite Blood Cells

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DefinitionPortion of plasma fraction of autologous blood having platelet concentration

above baseline. In clinical use since 1987.

PRP properties

Growth factor agonist Mitogenic (cell division)

Chemotactic (cell movement) Tissue sealant

Suppression of Cytokine release Promote new capillary growth

Antimicrobial activity (limited)


A typical PRP treatment releases growth factors for about 5-7 days. By giving

patents Nano doses of single recombinant growth factors, the extracellular

microenvironment is sustained potentially boosting therapeutic effect and

healing.

In all repair processes, the catabolic mechanisms such as the overriding of

anabolic growth factors by Tumor Necrosis Factor (TNF) inevitably occurs

between day 6-12; by giving a TNF antagonist systemically can induce a

higher anabolic repair rate, increasing healing and regeneration of tissue

between clinical appointments.

PRP Proteins

Stromal Cell Derived Factor 1 (SDF-1)

Vascular Endothelial Growth Factor (VEGF)

Platelet Derived Growth Factors (PDGF)

Transforming Growth Factors (TGF-beta)

Platelet Factor 4 (PF4)

Interleukin 1 (IL-1)

Platelet Derived Angiogenesis Factor (PDAF)

Epidermal Growth Factor (EGF)

Platelet Derived Endothelial Growth Factor (PDEGF)

Epithelial Cell Growth Factor (ECGF)

Insulin-Like Growth Factor (IGF)

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Activated platelets are critical to recruiting stem cells

Dr. C. David B. M. Harrell, OF,

FRIPH

SDF-1

VEGF

SDF-1 -recruits progenitor cells for tissue regeneration

VEGF –critical to vasculogenesis

SDF-1

SDF-1

SDF-1

SDF-1

SDF-1

VEGF

VEGF

VEGF SDF-1

SDF-1

SDF-1

Bone marrow cells

PRP Treatments

Soft tissue injuries

Disorders of the shoulder including bursitis and rotator cuff tears.

Tendonitis of a variety of tendons (Tennis Elbow, Achilles Tendonitis, and Heel Spur Syndrome).

Muscle tears, sprains, trigger points.

Cartilage injuries

Meniscus tears of the knee.

Mild to moderate degenerative arthritis of various joints.

Spinal disorders, especially facet joints.

Clinical cases

Avascular Necrosis (area of dead bone)

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Clinical cases

Frequently Asked Questions

Where do you take the stem cells from?Your stem cells can be safely removed from your pelvis and the fat on either your belly

or hip areas. Some stem cells can also be harvested from blood (VSEL). Small needles

are used to remove a piece of bone marrow and some fat (mini-liposuction).

Don’t I need the stem cells where you are taking them from?No, you have plenty more stem cells in these areas. When you remove stem cells, new

ones are formed to replace them.

How long does it take for stem cells to work?After your doctor injects the stem cells where they are needed, they go to work right

away. They will continue the repair process for up to1 year or longer. This does not

mean that you have to wait for pain relief. Patients typically feel pain relief in the first

few weeks to months.


Can I still have surgery if this procedure fails?Yes, none of our procedures would impact your options to have surgery in the future.

Do I have to take time off work for this procedure?Our BMAC procedure takes 2-4 hours to complete. So, we do recommend that you take

the day off from work. Most patients have no difficulty returning to work the next day.

When do I return to normal activity?You can return to most of your normal activities immediately. Depending on where the

Stem Cells were injected, you may feel some soreness or stiffness.

How can you tell if I am a candidate for the procedure?We will review your radiology studies, medical history, and perform a focused

examination to determine if you are a candidate for our procedures.

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What do you do with my blood or bone marrow to get the stem cells?

In some cases, we remove a small amount of bone marrow, fat or blood, we placed

them into a machine called a centrifuge to separate your stem cells and platelets from

the other cells. Other times, we use specialized needles which can select the stem cells.

How painful is the procedure to remove my stem cells and inject them?

You doctor will use an anesthetic while your stem cells are removed and injected. Most

patients experience very little discomfort during the procedure.

What are the success rates?

The great majority of our patients are very satisfied and would do the procedure again.

Success rates vary by the severity of the condition, type of joint, age of the patient, etc.

Conclusion

Regenerative Medicine includes:

PRP therapies joint pain

Bone Marrow and Adipose therapy for regenerative

Therapies

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fri halland 345 - baptist health south florida · tendonitis of a variety of tendons (tennis elbow,...

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