minden pookies study guide 3

what is stem cell medicine

- a broad field of medicine that involved the use of stem cells or stem cell biology to treat disorders

- stem cell therapy

- activation of endogenous stem cells

stem cell therapy

- treating a patient by transplanting new stem cells into the body

activation of endogenous stem cells

- pharmacologically activating the patients' own adult stem cells to promote repair [type of regenerative medicine]

embryonic stem cells

- pluripotent: can be come almost any cell type

- advantage is high flexibility

- limitation is ethical

adult stem cells

- multipotent: limited differentiation

- advantages are lower ethical concerns

- also lower immune rejections, especially if autologous [from same patient]

- ex: hematopoietic stem cells [HSCs used for bone marrow transplants]

induced pluripotent stem cells [iPS]

- adult cells reprogrammed to a pluripotent state

- fewer ethical concerns and potential autologous therapy are advantages

- limitation is that the safety is still being studied

stem cell therapies that are already FDA approved and in routine clinical use

- hematopoietic stem cell transplantation [bone marrow, peripheral blood, and cord blood]

- used for leukemia, lymphoma, bone marrow failure syndromes [BMF], and certain genetic blood disorders

most cell therapies are still in

- clinical trials

- mostly use adult cells: HSCs and MSCs

- many target non-hematologic diseases

- many of these are in early clinical phases [phase 1 and 2], but some have advanced to later stages

non-hematologic diseases

- heart disease, diabetes, spinal cord injury, MS, epilepsy

major challenges of stem cell therapy

- insufficient regulation

- insufficient education

- technical challenges

- immune rejection

- side effects

insufficient regulation

- some treatments are not FDA-approved but still marketed

insufficient education

- patients may have unrealistic expectations

- literature about stem cells may be confusing

- it may be unclear what kinds of stem cells are used for research studies that patients see

difficulties with stem cells

- isolation

- growing the cells

- differentiate them properly

- get cells to integrate properly

undifferentiated cells may form

- tumors

immune rejection

- body may attack transplanted cells

- autologous therapy helps but it is not always possible

side effects

- risk of tumor formation and other unknown long-term effects

Diseases and applications of stem cell therapy

- blood disorders [most established use of stem cells]

- Parkinson's disease [PD, a neurodegenerative disease]

- Alzheimer's disease [AD, neurodegenerative disease]

- multiple sclerosis [MS]

- eye disorders

- skin damage/burns

- organ transplantation

- HIV

- heart failure

- osteoarthritis

Hematopoietic stem cell transplant [HSCT]

- an example of a blood disorder use for stem cell therapy

- destroy diseased bone marrow [cancer, leukemia, other blood disorders]

- transplant healthy stem cells

- cells rebuild blood + immune system

- the goal is to replace defective cells

- has been used for decades

What is Parkinson's disease?

- loss of dopamine-producing neurons

- tremors

- stiffness

- loss of movement control

what are the dopamine-producing neurons lost in Parkinson's

- A9 DA neurons

current treatments for PD

- Levodopa [L-Dopa] to replace dopamine

- Deep brain stimulation [DBS]

problem with levodopa

- helps for a while but does not stop neuron loss

stem cell goal in PD

- replace lost dopamine neurons by using stem cells

the new cell requirements for stem cell treatments for PD

- differentiate into the correct neuron type

- be delivered to the correct brain region

- be capable of long-term survival

- not form tumors

studies done in animals regarding stem cell use in PD step 1

- iPS cells were generated from fibroblasts from monkey models of PD

studies done in animals regarding stem cell use in PD step 2

- cells were differentiated into dopamine [DA] neurons

studies done in animals regarding stem cell use in PD step 3

- these neurons were transplanted back into the monkeys [autologous] or into other monkeys [allogenic]

studies done in animals regarding stem cell use in PD step 4

- autologous recipients showed improved movement and decreased signs of depression

Alzheimer's disease key features

- neurodegeneration affecting many brain areas

- protein buildup

- no cure

- stem cell therapy is still experimental

protein buildup in AD

- amyloid plaques

- Tau tangles

challenges with AD

- many cell types affected, unlike PD, where only one is affected

- need correct integration of cells in brain

- disease environment might damage new cells

MS key features

- immune system attacks myelin

- myelin is normally produced by oligodendrocytes and it insulates nerves

MS symptoms

- weakness, numbness, paralysis, cognitive issues

stem cell strategies for MS

- immune reset using HSCs [most promising]

- immunomodulation using MSCs

- remyelination

immune reset using HSCs goal

- this method uses autologous HSCT

- resets the immune system

immune reset using HSCs step 1

- harvest the patient's own HSCs

immune reset using HSCs step 2

- use high-dose chemotherapy to eliminate autoreactive immune cells that destroy the patient's own myelin

immune reset using HSCs step 3

- re-infuse the patient with their own stem cells

immune reset using HSCs step 4

- the immune system regenerates, and this somehow resets the immune system

immune reset using HSCs step 5

- DOES NOT repair myelin directly, but it reduces autoimmune attack and has been successful for some patients

immune reset using HSCs step 6

- this method is currently used in specialized centers for aggressive MS, but does not yet have specific FDA approval for MS

immunomodulation using MSCs

- MSCs are sourced from the patient's bone marrow or adipose tissue

- MSCs do not replace oligodendrocytes, but they have been shown to reduce the immune system and inhibit inflammation

- due to paracrine signaling, where the MSCs are thought to secrete signals that reduce T cell activation and production of inflammatory cytokines

- mixed results

- this method is still under investigation, but HSCT method so far seems to be more promising

Remyelination in MS

- use iPS cells derived from skin cells to replace damaged oligodendrocytes

- still in early preclinical stages

eye disorders

- macular degeneration [AMD]

- corneal damage

macular degeneration [AMD]

- damage to the retina [specifically, damage to the retinal pigment epithelial {RPE} cells]

stem cell approach AMD step 1

- use stem cells to replace RPE cells, inject these cells into the retina

stem cell approach AMD step 2

- these cells can come from iPS cells that are differentiated into RPE cells

stem cell approach AMD step 3

- protocols have been developed to differentiate ES cells into RPE cells for treatment of AMD

stem cell approach AMD step 4

- another study used patient-derived iPS cells that were differentiated into RPE and transplanted into the retina

stem cell approach AMD step 5

- these studies are in experimental stages or in clinical trials

corneal damage stem cell therapy

- a type of stem cell treatment under investigation for corneal damage involves the limbal system stem cells

- limbal stem cell therapy

limbus zone

- zone of tissue that surrounds the iris

limbal stem cell therapy step 1

- limbal stem cells can be isolated from the good eye or from a donor and added to the iris of the affected eye

limbal stem cell therapy step 2

- once transplanted, these cells may have the ability to regenerate the different layers that make up the cornea

limbal stem cell therapy step 3

- these types of studies are still in preclinical studies, in some cases, in clinical trials

some ideas for using stem cells to repair damaged/burned skin

- grow the patient's skin cells in the lab

- use them to create artificial skin

- iPS cells may be a better new option

- iPS cells can also be used to create artificial skin

- banking iPS cells may allow patients to have a strong genetic match

organ transplantation problem

- not enough donor organs

organ transplantation solution

- replace specific cells instead of the whole organ

- these stem cells would be differentiated before being used

- stem cells may repair tissues

- stem cells main also be genetically modified to correct genetic abnormalities

How does HIV work

- HIV is a virus that causes AIDs

- the HIV virus uses a combination a receptor [CD4] and coreceptor [CCR5] to enter the cell

can stem cells prevent AIDs?

- some patients who have HIV AIDs were unexpectedly cured after stem cell transplants that were done for reasons unrelated to their HIV AIDs

- this result was due to genetic mutation in CCR5 genes of donor cells, thereby blocking viral entry

- shows potential for future therapies

heart failure

- a condition where the heart cannot pump efficiently

DREAM-HF trial

- involved the use of MSCs

- used for heart failure

- MSCs from donors were injected into the heart muscle [myocardium] of patients

MSCs in DREAM-HF trial may

- reduce inflammation

- improve outcomes

- results were promising, but nor perfect so more testing needed

Osteoarthritis

- joint degradation

MSCs in osteoarthritis

- MSCs may be promising for treatment

- may develop into chondrocytes

- may reduce inflammation

- still in experimental stages/clinical trials

The type of neuron that is deficient in Parkinson's Disease is:

A. Dopamine neurons

B. Serotonin neuron

C. Limbus stem cells

D. MSC stem cells

E. A and D

A. Dopamine neurons

In the "Immune Reset" strategy for Multiple Sclerosis, clinicians use a patient's own __________ to regenerate the patient's immune system

hematopoietic stem cells [HSCs]

The cell type that produces myelin is:

A. oligodendrocytes

B. Dopamine neurons

C. Serotonin-producing neurons

D. MSCs

E. Muscle cells

A. oligodendrocytes

Which type of cells would be the most promising for the treatment of AMD?

A. Limbus cells

B. Retinal pigment epithelial cells

C. Mesenchymal cells

D. Keratinocytes

E. Both A and B

B. retinal pigment epithelial cells

Functional cures for HIV have been observed in patients who received stem cell transplants from donors possessing an inactivating mutation in the _________ gene

CCR5

________________ are cells that secrete components that make up cartilage and that are highly significant in osteoarthritis

- chondrocytes