Stem Cells and Regenerative Medicine Flashcards

1
Q

What are Stem Cells

A
  • Can differentiate into many different cell types
  • Capable of self-renewal via cell division
  • Provide new cells as an organism grows and can replace cells that are damaged or lost
  • Several different types of stem cells: embryonic, adult and induced pluripotent stem cells
  • Targeted by researchers for their therapeutic potential
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2
Q

What conditions can be treated with stem cell therapy

A
  • Blindness
  • Wound healing
  • Myocardial Infarction
  • Spinal cord injury
  • cancers
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3
Q

List the three stem cell sources

A
  • Adult stem cells
  • Embryonic stem cells
  • Induced pluripotent stem cells
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4
Q

What roles do adult stem cells have

A
  • replace damaged cells
  • reduced function as can only differentiate into a few cell types
  • Multipotent tissue-specific cells
  • Can be extracted and manipulated in-vitro
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5
Q

What roles do Embryonic stem cells have

A
  • can become all cell types
  • pluripotent
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6
Q

What roles do induced pluripotent stem cells have

A
  • lab made by converting normal cells by exposing them to chemicals
  • reduced graft rejection
  • used for organ models
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7
Q

What can all stem cells be used for

A
  • Model for basic and translational studies
  • Disease modelling
  • Drug screening
  • Cell replacement therapy
  • Cell differentiation - 3D organoid models
  • Developmental biology
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8
Q

What are stem cell niches

A

Tissue-specific stem cells are maintained in special supportive microenvironments called stem cell niches.

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9
Q

List some stem cell niches

A
  • Supporting Extracellular matrix
  • neighbouring niche cells
  • secreted soluble signalling factors (e.g. growth factors and cytokines)
  • physical parameters; shear stress, tissue stiffness, and topography),
  • environmental signals (metabolites, hypoxia, inflammation, etc.).
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10
Q

Compare the properties of each stem cells

A

Embryonic Stem Cells:

  • Pluripotent
  • High risk of tumour creation
  • High risk of rejection
  • high cell potency
  • low probability of mutation

Adult stem cells:

  • Oligopotent, Unipotent
  • Less risk of tumour creation
  • low risk of rejection
  • A limited number of cells may be obtained
  • high mutation risk

Induced pluripotent stem cells:

  • less growth than embryonic stem cells
  • less risk of tumour formation
  • low risk of rejection
  • A limited number of cells may be obtained
  • high mutation risk
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11
Q

How can you generate iPSC

A
  • Adult somatic cells are taken from a donor
  • The cells are treated with reprogramming factors
  • Then transferred to ESCs media
  • They undergo Morphological and expressional transitions
  • the cells then mature to iPSCs
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12
Q

What transcription facts are use and what does each do

A
  • c-Myc promotes DNA replication and relaxes chromatin structure
  • allows Oct3/4 to access its target genes.
  • Sox2 and Klf4 also co-operate with Oct3/4 to activate target genes
  • these encode transcription factors which establish the pluripotent transcription factor network
  • result in the activation of the epigenetic processes (more open chromatin) that establish the pluripotent epigenome.
  • The iPS cells have a similar global gene expression profile to that of ES cells.
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13
Q

How can stem cells be tracked in the body

A

A fluorescent reporter gene is inserted into the cells

the cells can be tracked where they go to non-invasively

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14
Q

List the 2 CVS regeneration strategies

A
  • Cell transplantation approaches to promote cardiac regeneration and repair
  • Therapies based on direct stimulation of endogenous cardiomyocyte production
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15
Q

Explain models which regenerate cardiac tissue

A

Zebrafish, amphibians and some neonatal mice can regenerate the heart.

  • Re-expression of developmental programmes
  • Reactivation of epicardium and endocardium
  • cardiomyocyte redifferentiation
  • fibrin clot formation
  • cardiomyocyte proliferation and heart regeneration
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16
Q

Explain the immune response in CVS regeneration

A

In normal mice, after monocyte-derived macrophage infiltration, there is limited revascularization and scar tissue is formed.

In neonatal mice, there is embryonic macrophage infiltration and growth and regeneration of the heart.

17
Q

Explain the lymphatic response in CVS regeneration

A

In endogenous lymphatic response, there is insufficient clearing of tissue fluid leading to inflammation and oedema.

VEGFC-C156S administration causes augmented lymphatic response and clearance of excess tissue fluid

18
Q

How can you make cardiac lineages from iPSC cells

A
  • Somatic cells to iPSCS by the delivery of Yamanaka factors
  • Into pre-cardiac mesoderm with GSK-3B inhibition
  • Into cardiovascular progenitor cells with Ant signalling inhibition
  • These cells can become all the cells of the heart via other signalling pathways
19
Q

Describe stem cell transplantation

A

Induced pluripotent stem cells (iPSCs) are a potential source of autologous patient-specific cardiomyocytes for cardiac repair providing a major benefit over other sources of cells in terms of immune rejection.

Grafted cardiomyocytes (GFP+) survived for 12 weeks with no evidence of immune rejection. Showed:
1.electrical coupling with host cardiomyocytes
2.improved cardiac contractile function at 4 and 12 weeks after transplantation
But incidence of ventricular tachycardia increased compared to controls.

20
Q

What is the role of Myocardial thymosin

A

Necessary for epicardial migration, coronary vasculature and cardiomyocyte survival

Importantly Tb4 addition to adult hearts can stimulate epicardial outgrowth and neovascualarisation

21
Q

What is FSTL1

A

FSTL1 in the epicardium has potent cardiogenic activity
Epicardial expression is lost after MI
If restored experimentally, it promotes regeneration of pre-existing cardiomyocytes in mouse and pig models

22
Q

List some Stem cell-based therapy for cancer

A
  • Chemo/radiotherapy kills cancerous cells. Transplantation of stem cells reconstitutes healthy cells
  • Clinical trials for other tumour types; brain and breast cancer, neuroblastoma, sarcoma
  • Effector immune cells from iPSC/ESCs e.g. engineered T and NK cells targeted for immunotherapy.
  • production of anti-cancer vaccines
  • MSCs/NSCs deliver genes, nanoparticles, and oncolytic viruses to tumour niche due to intrinsic tumour tropism.
  • exosomes extracted from the culture of drug-priming MSCs/NSCs can target the drugs to tumour sites.
  • Mutation correction in vitro, drug testing in vitro before replacement in vivo.
23
Q

List some Stem cell-based therapy for burns

A

Replace lost skin cell types, speeding up endogenous healing. Generate ECM and produce paracrine signals which aid healing.

  • Fetal fibroblasts (from ESCs); improve skin repair due to the high expansion ability, low immunogenicity, and intense secretion of bioactive substances such asFGFs, VEGFs, KGFs
  • Epidermal stem cells; high proliferation rate and easy access and keep their potency and differentiation potential for long periods. Generate most skin cell types for repair and regeneration
  • Mesenchymal stem cells; They have a high differentiation potential and a certain degree of plasticity. Migrate to the injured tissues, differentiate, and regulate the tissue regeneration by the production of growth factors, cytokines, and chemokines
  • iPSCs; can be differentiated into dermal fibroblasts, keratinocytes, and melanocytes.
24
Q

List some Stem cell-based therapy for Eye injuries (cornea)

A
  • Stem cells at the edge of the cornea, limbal stem cells are responsible for making new corneal cells to replace damaged ones.
  • If these stem cells are lost due to injury or disease, the cornea can no longer be repaired. This affects the ability of light to enter the eye, resulting in a significant loss of vision.
  • Limbal stem cells are collected from an adequately healthy donor eye, and are expanded in the laboratory to sufficient numbers and transplanted into the damaged eye.
  • Repairs the cornea and permanently restores vision.
  • To avoid immune rejection this treatment only works if the patient has a healthy section of limbus from which to collect the limbal stem cells.
  • iPSC cells can be induced to make corneal epithelial cells for transplant and exposure to the right signals can transfor fibroblast cells into limbal stem cells
25
Q

List some Stem cell-based therapy for Eye injuries (retina)

A
  • Retinal pigment epithelium (RPE) is a single layer of post-mitotic cells, acting as a selective barrier to and a vegetative regulator of the overlying photoreceptor layer,
  • RPE has a key role in retina maintenance and parts of the retina can die without a functional RPE leading to loss of vision
  • RPE cells can be damaged in a variety of diseases such as: age-related macular degeneration (AMD), retinitis pigmentosa and Leber’s congenital aneurosis.
  • RPE cells have been made from both ESC and iPSC
26
Q

List some Stem cell-based therapy for Spinal injury

A
  • Biopsy of somatic cells from donor
  • Reprogram to iPSC
  • Differentiate into neural stem cells
  • Implant cells into the injury location
  • cells differentiate into many types to tapir the injury