Cellular Therapies Flashcards

Question

what is the therapeutic potential of MSC?

Answer 1

Comes from their ability to: secrete solutble factors crucial for cell survival and proliferation modulate immune response differentiate into various cell types transdifferentiate-non mesoderm migrate to sites of injurt in response to cell signals

Answer 2

Globally: 463 registered clinical trials 296 employ autologous MSC ``` Cover wide range of therapeutic applications: Cardiovascular Autoimmune Osteoarthritis Liver disorders GvHD ``` Major sources of MSC in clinical trials: Bone marrow Umbilical cord Adipose tissue No approved treatments using MSC

Answer 3

Commercial companies provide services to isolate/store stem cells UK: Future Health Biobank, Cell4life, Precious cells Biological insurance: individual/child/ family member develops a disease in the future treatable by stem cells One off charge (+maintenance fees) ``` Cells sources: umbilical cord placenta blood adipose tissues dental pulp from child's teeth ```

Answer 4

Specialized cells unable to proliferate and have reached the final stage of development

Answer 5

donor platelet transfusions platelet deficiency due: disease treatment related- chemotherapy life threatening bleeding - injur injury or trauma autologous platelet rich plasma therapy

Answer 6

platelets rich source of growth factors which stimulate development soft tissue/bone cells procedure claims to initiate faster healing response blood collected, centrifuged to seperte blood, plateley rich plasma collected, injected into injured area ``` used in treatment of ortho conditions: Osteoarthritis Tendonitis Tendon tears Nerve injury Professional athletes with muscle and ligament injuries (Tiger Woods ```

Answer 7

red cell transfusions treat anaemia: heavy blood loss bone marrow not producing enough red cells (chemo, leukaemia/sickle cell) autologous erthyrocyte encapuslated enzyme replacement therapy

Answer 8

Under clinical development at SGUL for treatment of diseases due to inherited enzyme deficiencies 1) deficient enzyme encapsulated in patients erythrocytes in vitro 2) intravenously administered to the patient 3) permit elimination of pathological plasma metabolites: pathologically elevated plasma metabolite permeate cell membrane encapsulated enzyme catalyses substrate--> normal product normal product exits cell to enter usual metabolic pathway this is applicable to disorders where pathologically high metabolite permeate erythrocyte membrane

Answer 9

majority licesence enzyme replacement therapies (ERT) High enzyme activity half-life: - short plasma half-life, frequent infusions:maintain therapeutic effective levels low immunogenic reactions and production of anti-enzyme antibodies: anti-enzyme antibody production leads to loss of therapeutic efficacy allergic reactions

Answer 10

1) erythrocytes + exogenous enzyme undergo hypo-osmotic dialysis 2) erythrocytes swell; formation of pores in membran 3) exogenous enzyme enters cell and iso-osmotic dialysis occurs. 4) erthyrocytes reseal, encapsulating therapeutic agent

Answer 11

treatment two autosomal recessive metabolic disorders: 1)Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE) Product: erythrocyte encapsulated thymidine phophorylase (EE-TP) 2) Adenosine deaminase deficiency product: erythrocyte encapsulated adenosine deaminase (EE-ADA)

Answer 12

mutatuon in the nuclear gene (TYMP) which encodes for thymidine phosphorylase (TP) mitochondiral deoxynucleotide pool imbalance leading to: 1) increased [plasma] of thymidine and deoxyuridine 2) impaired replication/repair leading to multiple deletions, point mutations and depletion Ultimarley loss of mitochondiral respiratory chain function.

Answer 13

Mainly effects GI and nervous system. ``` GI symptoms: Severe gastrointestinal dysmotility Psuedo-obstruction Nausea/vomiting Chronic abdominal pain Premature satiety LEADS TO: Malabsorption Bacterial over-growth Intestinal perforation Loss of muscle mass ``` Neuro symptoms: Leukoencephalopathy Demyelination nerve fibres Initially patchy Ocular symptoms Ptosis Loss of vision Peripheral neuropathy Numbness Muscle weakness Hearing loss patients die avg age 37 combo of nut and neuromusc failure

Answer 14

Bax et al (2013) demonstrated: Clinical improvements in sensory ataxia (balance and gait) & fine finger functioning Increase in body weight Walk longer distances, climb stairs without assistance, tie shoe laces Returned to public performances as guitar player in a band Previously reported numbness in hands/feet resolved

Answer 15

1) gene modified autologous stem cell therapies | 2) engineered T-cell therapies

Answer 16

autologous stem cells collected from patient and genetically corrected prior to reinfusion eg: HSC-directed gene therapy HSCs are multipotent, capable of generating entire epctrum of blood/lymphoid cells suitable target therapies for: haematological malignancies iherited blood disorders

Answer 17

approved 2016: treatment of inherited severe combined immunodeficiency disease: adenosine deaminase deficiency 1)HSCs isolated from bone marrow 2)CD34+ cells expanded in culture Transduces with retroviral vector expressing fucntional copy of defective gene (adenosine deaminase) 3) endogenous bone marrow progenitors eliminated to favour engraftment Modified stem cells infused. Gene-corrected stem cells reconsititute lymphoid lineages/restore immune function

Answer 18

tumour cells often recognised as 'self' - prevents T cells from recognizing tumour proteins solution: genetically alter T-cells to create recognition receptors unique to patients tumour altered t cells expanded in culture and infused into patient which seek out/destroy tumour cells two approached: t-cell receptor therapies (TCR) chimeric antigen receptor (CAR-T) therapies

Answer 19

1) peripheral blood lymphocytes removed from patient 2) cells transduced with viral vector containing contruct encoding for tumour reactive TCR Expanded in culture Infused into patient 3) Infused cells express modified TCR on surface 4) recognise tumour-specific proteins on the inside of cell through encountering tumour antigen peptide processed and presented on cell surface 5)tumour destruction

Answer 20

chimeric=composed of parts from two or more different sources CAR= artificial receptor that links: 1)antibody molecule:polypeptide sequences of light and heavy chain from antibody recognises target proteins expressed on cancer cell surface and 2)t-cell signalling machinery of t-cell receptor: on binding to target- clonal expansion, secretion of cytokines to recruit immune system, destruction of tumour cell

Answer 21

1) peripheral blood lympocytes removed from patient 2)cells transduced with viral vector containing CAR construct expanded in culture infudes into patient 3)expressed CAR recognises external antigen leading to death of targeted cancer cells

Answer 22

Turning cells into effective/safe/ affordable therapies poses many challenges:

Cellular Therapies Flashcards

(46 cards)