Regenerative medicine Flashcards
(19 cards)
What are the four ways immune rejection can be avoided in hPSC therapies?
Four main strategies to circumvent immunosuppression of patients:
(1) autologous transplantation of the patients’ own cells,
(2) use of HLA-haplotyped hiPSC banks for HLA-matching,
(3) gene editing of hypoimmune cell lines, which can escape host immune cell recognition
(4) immunoprotective encapsulation of transplanted cells to physically protect the transplant from host immune cells.
What are organs-on-chips?
They are systems containing engineered or natural miniature tissues grown inside microfluidic chips
Next-generation experimental platform to investigate human pathophysiology and the effect of therapeutics in the body
They offer an advantage over other models bc they can be made with a patients own cells, allowing screening of drugs
Disadvantages are they are technically complex and expensive, and lack physiological complexity
What is regenerative medicine?
Aims to repair or replace cells/ tissue/organs to restore function
Can include range of technqiues such as stem cell therapy, tissue engineering, and gene therapy
What are the different types of stem cells?
Embryonic stem cells: undifferentiated cells derived from a pre-implantation embryo that are pluripotent
Somatic/Tissue stem cells (unipotent, multipotent, induced pluriipotent-iPS): While tissue stem cells are not naturally pluripotent, it is now possible to induce this feature by artificially activating specific genes.
What are the different types of regenerative medicine?
- Tissue engineering and biomaterials
- Cellular therapies.
- Medical devices and artificial organs
What are limiations of translating cell therapies to the clinic?
- Limitations of preclinical animal models, anatomical differences may cause false negative results in animal models (eg veins r too small for a therapy to travel through effectively)
- Hard to track cell delivery and engraftment: impossible to non-invasively image donor cells post-transplantation
- Potential for immune rejection
How might advancements in gene editing contribute to developing regenerative medicine?
- Improve tracking of cell delivery: In glioblastoma patient study, reporter gene expression enabled the trafficking of the therapeutic cells to the tumour site with PET/CT imaging
How is CAR T-cell therapy an example of regenerative medicine?
It is modifying a patient’s own cells to restore or enhance physiological function (aka immune system)
CAR T-cell therapy uses the patient’s own T-cells, which are genetically engineered to express chimeric antigen receptors (CARs) that target specific cancer antigens, thus it is a uses a combination of gene and cell therapy technologies.
What are examples of autologus cell-therapy?
CAR T-therapy for blood cancer
Exa-cel for sickle cell disease and beta-thalassemia
What are examples of allogenic cell-therapy?
What is Exa-cel?
Autologous gene-edited hematopoietic stem cell (HSC) therapy for sickle cell disease (SCD) or Transfusion-dependent Beta-thalassemia (TDT)
CRISPR-Cas9 gene editing is used to disable a repressor gene (BCL11A) that normally suppresses fetal hemoglobin (HbF) production
The patient begins producing red blood cells with high levels of HbF, which compensates for the defective hemoglobin in SCD or TDT
What are developing strategies to treat myocardial infarction?
Gene therapy: MicroRNAs like miR-590 and miR-199a have been shown to stimulate cardiomyocyte proliferation and improve cardiac function post-MI
Cell therapy: Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can be differentiated into cardiomyocytes and transplanted to replace damaged tissue
Tissue engineering: Engineered Heart Tissues (EHTs): Constructing 3D cardiac tissues (engiusing scaffolds and cardiomyocytes can create patches that integrate with native myocardium and restore function.
Myocardial infarction (MI) causes the loss of millions of cardiomyocytes, and current treatments do not address this root issue. Only treatment for ischemic heart disease is heart transplant
How might stem cell therapy be used to treat parkinsons disease?
Embryonic stem cells (ESCs), Induced pluripotent stem cells (iPSCs), Neural stem cells (NSCs) induced into dopaminergic neurons to replace dying ones in the striatum
Cons: tumor risk, immune rejection, synaptic integration, ethical concerns w embryonic stem cells
A notable trial in Japan used iPSC-derived dopamine progenitors, showing early signs of safety and feasibility
How might stem cell therapy be used to treat spinal chord injury?
- Cell replacement: using neural stem/progenitor cells (NSCs) or pluripotent stem cell-derived neurons
- Remylination: using oligodendrocyte precursor cells (OPCs)
- Neuroprotection and Trophic Support: using Stem cells (especially mesenchymal stem cells, or MSCs) secrete neurotrophic factors like BDNF, NGF, and anti-inflammatory cytokines
- Scar Modulation and Axon Growth Promotion: using stem cells embedded in biomaterials (hydrogels, scaffolds)
How might stem cell therapy be used to treat Multiple sclerosis (MS)?
- Chemotherapy and Hematopoietic Stem Cell Transplant (HSCT)
- Remylination and neuroprotection: Mesenchymal (MSCs)/neural (NSCs) stem cells or iPSC- or ESC-derived oligodendrocyte precursor cells (OPCs)
Cons: risk of infection from immunosuppression, expensive, not effective in primary or secondary MS
How are stem cells being used to treat age-related macular degeneration?
Use human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE)
Phase 1 trial implanted hESC-RPE in wet-AMD patients
Improved visual acuity and retinal sensitivity over 12 months
Future research needed to confirm long-term safety and efficacy
Describe potential of iPSC-derived cardiomyocytes for disease modelling and drug discovery
Can be used as personalised in vitro disease models
Useful for inherited cardiac diseases (arrhythmogenic syndromes/channelopathies)
Useful for drug screening, and development of personalised therapies
Whats the safety profile of human embryonic stem cell therapy?
One study in 2017 found no serious adverse affects during hESC therapy for terminal conditions (inc neurological disorders) in 33 patients
But follow up is needed to assess potential for delayed adverse effects
