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Stem Cell, Organoids, Burn Injury, Tissue Engineering for Regenering -…
Stem Cell
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Turning Point
Despite potential mutagenic risks, current reprogramming methods produce fully pluripotent iPSCs with minimal genomic alterations.
iPSCs offer an unlimited source for tissue replacement without the need for embryos, derived from the patient's own cells, thus avoiding immune rejection.
This process involves oncogene expression like Myc & Klf4, along with downregulation of genes promoting genome stability sich as p53, & histome alteration.
Tissue-specific genomic methylation influences transcription, impacting induced pluripotency.
Direct reprogramming induces pluripotency in differentiated cells, yielding iPSC lines capable of forming all cell types.
Initially sourced from fibroblasts, researchers explored other cell types like peripheral blood cels, keratinocytes, & renal epithelial cells.
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Cultured Meat
Adult Stem Cells
These cells are isolated from specific tissues & can differentiate into a restricted number of cell types relevant to meat production
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Advantages of PSCs
PSCs, including ESCs & iPSCs offer indefinite proliferative capabilities & high growth rates, essential for scaled production
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Challenges
Alternative substances to replace expensive growth factors & serum proteins are being explored but are in early stages of development
The goal of achieving meat tissue with nutritional value & sensory properties similar to animal-derived meat is yet to be fully realised
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Culture medium costs a lot, edible microcarriers are explored to reduce costs
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Production Process
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Stem cells can be obtained from b\various animal species & differentiated into muscle, fat, & other relevant cell types
Expansion & seeding of stem cells in 3D matrices, followed by differentiation into desired tissue types
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Biology
Somatic stem cells, found throughout the body, aid in healing & cell replacement with limited differentiation options.
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Human embryonic stem cells (hESCS) are pluripotent & derived from their inner cell mass (ICM) of blastocysts.
Blastocysts, formed after fertilization, contain embryonic stem cells lining their wall.
hESC Derivation & Media
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Cell passaging involves enzymatic dissociation, manual passage, trypsin utilization / EDTA treatment.
Feeder layers like MEPS & Serum are traditionally used, but feeder-free culture with serum replacement & laminin is effective.
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Use in Medicine
Pluripotency : The ability of stem cells to differentiate into various cell types is crucial for treating various medical conditions
Applications : Stem cell therapies are being explored for treating spinal cord injury, heart failure, retinal & macular degeneration, tendon ruptures, & diabetes type 1
Potential of Stem Cells : Stem cells play a signifiant role in developing restorative medicine & reveal insights into human development
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Cell-Based Therapies
Induced Differentiation : Stem cells can be induced to become specific cell types needed for tissue repair
Conditions Benefiting from Therapy : This includes macular degenerations, strokes, osteoarthritis, neurodegenerative diseases, & diabetes
Tissue Banks
iPSCs & tissue banks : iPSCs offer unlimited propagation & differentiation abilities, making them an essential source for medical examination
Advantages of Banking : iPSCs can be stored in a tissue bank, offering a solution for future medical needs
Fertility Diseases
iPSCs for Sperm & Egg Formation : iPSCs have shown potential in forming sperm & eggs in mice, indicating a possible pathway for infertility treatments in humans
Challenges : High efficiency, minimal risk of tumor formation & maturation of human sperm & eggs in lab conditions are critical
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Dentistry
Challenges in Dental Regeneration : Teeth present a complex structure for regenerative medicine, but stem cells offer a promising alternative to synthetic materials
Potential Applications : Stem cells can be used for periodontal ligament regeneration, dentin regeneration, & enamel regeneration, with potential for dental pulp stem cells (DPSCs) & human exfoliated deciduous teeth (SHED) cells to be particularly useful
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Organoids
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Human & Animal Models
Ocular Morphology Differences : Mice hav >70% rod photoreceptors, contrasting with trichromatic human & non-human primate retinas, highlighting the importance of understanding rod photoreceptor fate choices for human retinogenesis
Phototransduction Machinery : The complex cascade of gene regulatory networks required for phototransduction machinery formation can be studied using retinal organoids for genetic manipulation & transcriptomic analysis
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Retinogenesis
Formation of the retinal lamellae, including 7 retinal cell types, starting with the division of the forebrain into telencephalon & diencephalon, leading to the formation of optic vesicles, precursors to the retinal pigment epithelium (RPE) & the neural retina (NR)
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Retinal Progenitor Cells (RPCs) : Differentiate into various retinal cell types, including RGCs, cone photoreceptor cells, & horizontal & amacrine cells, populating the ONL & forming synapse networks.
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Burn Injury
Epidemiology
Burn injuries are decreasing in high-income countries but remain high in low- and middle-income areas, with ~90% of burns occurring in these areas.
The WHO estimates 11 million burn injuries annually worldwide, with 180,000 fatalities.
Data on burn epidemiology are variable & inconsistent, with most data coming from high-income countries.
Burn injuries are more common in young children & working-age adults, with a bimodal age distribution in the USA.
Burn injuries lead to lifelong physical & psychological scarring, affecting mental health, wuality of life, work return, & mortality.
Flame burns are the majority of injuries in the USA, followed by scalds, chemical, & electrical burns.
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Quality of Life
Psychometric Quality : Doubt exists about the psychometric quality of several burn-specific instruments, including SF-36 domains being more sensitive than BSHS-B domains
New Instruments : The Brisbane Burn Scar Impact Profile, CARe burn scale, & LIBRE survey need further validation
Assessment Tools : Tools like BSHS, SF-36, & EQ-5D questionnaires assess HRQOL in adult patients after burn injuries.
Prognostication Models : Models predicting recovery of HRQOL after burn injury can inform patients & healthcare professionals on expected outcomes.
Health-Related Quality of Life : Reflects an individual's perception of how a condition affects health-related domains for physical, psychological, emotional & social wellbeing.
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Initial Injury
The natural healing process involves dynamic & overlapping phases, including an inflammatory, proliferative, & modelling phase.
The complex healing response is targeted towards dermal & epidermal regenartion, aiming to restore the skin barrier's closure, pliability & functionality.
The burn wound can be divided into 3 zones (coagulation, ischaemia, & hyperaemia).
Shock
The marked capillary leakage can be attributed to oxidative stress, damaging the vascular endothelium.
Burn injury depresses cardiac function within a few hours of injury, lasting ~24-48 hours, via oxidative stress & the release of inflammatory mediators.
Burn injury results in a distributive shock, characterized by severe tissue perfusion & oxygen delivery compromise due to marked capillary leakage.
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Children
Quality of Life Assessment : The burns outcome questionnaire for children (BOQO-5 & BOQ6-18) are valuable resources for quality of life assessment in children after burn injury.
Challenges : Factors like burn size & depth, hospital stay length, presence of facial & hand burns, comorbidity & long recovery time predict suboptimal HRQOL in children.
Employment & School After Injury : Return to work & school are important outcomes after burn care, with factors like burn severity hospital stay length, age, psychosocial & work-related factors predicting return to work.
Adults
Long-Term Effects : Patients with burn injuries experiencing hospital-acquired complications report lower physical component summary scores on the SF-12 for up to 24 months
Additional Instruments : Instruments like SWL, SWAP, & CIQ provide alternative options for assessing patient perceptions of their HRQOL
HRQOL Improvement : HRQOL improves over time, but some domains show delayed return to baseline after a burn injury
Hypermetabolic State
After an initial hypometabolism, a hypermetabolic state is observed in patients with severe burns, persisting for up to 36 months after the initial insult.
The hypermetabolic state is characterized by increase blood pressure, peripheral insulin resistance, & breakdown of glycogen, proteins & lipids.
Outlook
Future of Burn Care : Burn care must change to adjust to the challenges ahead, including epidemiology & prevention, development of international burn registries, accurate measurement of burn size & depth, prognosis, acute care, & long-term care.
Technological Advancements : New technologies need to be adopted in all phases of the recovery process to further improve burn outcomes, acutely & in the long term
Secondary Conditions
Long-Term Medical Consequences : Both minor & severe burn injuries result in increases long-term morbidity & mortality, as well as increased risk of hospital re-admission, long-term hospitalization, & prolonged hospital stay for musculoskeletal diseases.
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