tissue engineering 1

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tissue engineering

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119 Terms

1

tissue engineering

practice of combining scaffolds, cells, & biologically active molecules into functional tissues

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2

goal of tissue engineering

to assemble functional constructs that restore, maintain, or improve damaged tissues/whole organs

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3

regenerative medicine

broad field that includes tissue engineering but also incorporates research on self

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4

where and when was the term "tissue engineering" coined

nsf

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5

cells

building blocks of tissue

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6

tissues

basic unit of function in the body

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7

extracellular matrix

groups of cells make & secrete their own support structures

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8

matrix/scaffold

also acts as a relay station for various signaling molecules

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9

signal

each can start a chain of responses that determine what happens to the cell

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10

building a scaffold

proteins to plastics once created, cells w/ or w/o growth factors can be introduced right environment, tissue develops all mixed together, tissue self

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11

create new tissue used an existing scaffold

cells of donor organ are stripped and remaining collagen is used

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12

supplemental bladders, small arteries, skin grafts, cartilage, & trachea

have been implanted but procedures are still experimental & very costly

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13

complex organs

heart, lung, liver tissue

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14

complex tissues

useful in research, in drug development

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15

functioning human tissue

help screen medication candidates could speed up development save money, reduce # of animals used for research

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16

biomaterial

pigs intestine

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17

6 research areas of tissue engineering

  1. development of new biomaterials/scaffolds

  2. id of optimal cell sources

  3. biomolecules

  4. engineering methods & design

  5. functional assessment of engineering tissues

  6. informatics as applied to tissue engineering

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18

novel biomaterials

designed to direct the growth, differentiation, & organization of cells in the process of forming functional tissue by providing physical, chemical, & mechanical cues

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19

6 cell sources for tissue engineering

  1. autologous

  2. allogeneic

  3. syngeneic

  4. xenogeneic

  5. stem & progenitor

  6. genetically engineered

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20

stem cell research

involves stem cells, whether from embryonic, fetal, or adult sources, human & non

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21

2 stem cell research purpose

stem cells are isolated, derived, or cultures to develop cell/tissue therapies, studying cell differentiation

to understand the factors necessary to direct cell specialization to specific pathways, & other developmental studies

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NOT stem cell research

transgenic studies, gene knockout studies, generation of chimeric animals

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23

first Us clinical trial of pt

derived stem cell therapy

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24

first US pt receieves autologous stem cell therapy

to treat dry AMD

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25

5 examples of biomolecules

  1. angiogenic factors

  2. growth factors

  3. differentiation factors

  4. transcription factors

  5. bone morphogenic proteins

ex

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26

bioinformatics

including the application of tools & info from many areas of informatics to the design & characterization of engineered tissue

ex

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27

8 engineering design aspects

  1. 2d cell expansion/scale

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28

functional assessment of engineered tissues

new imaging tools for real

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29

what are NIH

funded researchers developing?

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30

what are NIH

funded researchers projects? (6)

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31

ex of engineered tissues that have been approved by the FDA

artificial skin & cartilage

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32

people in TE

  1. robert langer

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33

the pcr method

technique used to make many copies of a selected DNA sequence

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34

ECG, EKG electrocardiogram, electrocardiography

a recording of the electrical activity of the heart

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35

positron emission topography (pet)

an imaging technique used to see which brain areas are being activated while performing tasks

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36

GeneChip/RNA

seq gene expression study

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37

single cell transcriptomes analysis (scRNA

seq)

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38

retinal organoids

derived from induced pluripotent skill cells have the potential to be used for modeling human diseases

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39

(6) what are the fundamentals of tissue engineering?

  1. cells

  2. tissues

  3. homeostasis

  4. signaling

  5. ecm

  6. biomaterials

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40

(8) what are the tools of tissue engineering?

  1. microscopy

  2. bioimaging

  3. pcr

  4. dna sequencing

  5. gene expression profiling

  6. gene delviery/therapy

  7. bioMEMS

  8. nanotechnology

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41

quantitative cell & tissue biology

tissue organization, tissue dynamics, morphogenesis, stem cells, cellular fate processes, & their coordination

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42

cell & tissue characterization

high

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43

engineering methods & design

time constant analysis, scale

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44

clinical implementation

conventional approaches to tissue repair, host integration, & producing tissue

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45

overview of tissue engineered

based approach using 3d

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46

treating female infertility

healthy donor tissue/organ

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47

tissue engineered endometrium

inner lining membrane of the uterus

collagen i & matrigel cell

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48

causes of female infertility

chemo uterine injuries fallopian tube occlusion hysterectomy massive intrauterine adhesions congenital uterine malformations

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49

how can we fabricate tissue engineered grafts for female reproductive organ?

  1. biomaterial fabrication

  2. cell isolation & expansion

  3. cell seeding

  4. scaffold conditioning

  5. implantation

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50

layered approach

tissue engineered endometrium

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51

combined approach

tissue engineered endometrium

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52

bio printing strategies for bio fabrication

  1. extrusion bio printing

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53

why is TE necessary? (5)

  1. congenital abnormalities require tissue reconstruction

  2. most tissues cannot regenerate following a disease/injury

  3. even tissues that regenerate spontaneously may not completely do so if defects are large

  4. transplantation is limited by the scarcity if donor tissue

  5. permanent implants have a lot if success, but also lots of problems

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54

opportunities for commercialization

  1. biomaterials

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55

general criteria for product develpment

  1. fulfills unmet need in potentially large markets

  2. shows strong likelihood of technical feasibility, efficacy, & cost effectiveness

  3. unique to the market

  4. time to market less than five years

  5. cost to market within financial means without undue risk

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56

storage & transportation companies

integra life sciences corp lifecell corp

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57

where do we stand?

on market

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58

spinal muscular atrophy

caused by the deletion/mutation of the survival motor neuron 1 (smn1) gene

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59

smn1 gene

produces survival motor neuron protein that is critical for normal function of motor neurons

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60

zolgensma

designed to enable rapid & continuous expression of smn protein

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61

limited success

full regeneration of tissues that do not regenerate spontaneously has not been achieved (success with bone, engineered skin has no glands, hair/nerves)

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62

autografts

harvesting tissue from a pt's own body for transplanting into the same pt

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63

allografts

harvesting tissue from a donor, transplanting in a pt, deceased/living donors

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64

xenografts

removing tissue from animals from transplantation into a human

  • available supply, standardized products

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65

man made materials & devices

artificial heart, heart valves, prosthetic hips, etc.

  • fill short term needs

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66

stem cell therapy

the use of stem cells to treat/prevent a disease/condition

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67

what is a stem cell?

a single cell that can replicate itself/differentiate into many cell types

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68

why self

renew & differentiate?

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69

where are stem cells found?

embryonic stem cells (blastocyst

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70

embryonic stem (ES) cells: where we find them?

isolated from very young mammalian embryos blastocyst

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71

embryonic stem (ES) cells: what can they do?

pluripotent

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72

embryonic stem (ES) cells: challenges

tumorigenicity immune rejection genomic stability limited sources heterogeneity

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73

tissue stem cells: where we find them?

surface of the eye, brain, breast, skin, testicles, intestines, muscles, bone marrow

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74

tissue stem cells: why we need them?

essential for keeping us fit & healthy replace cells that are damages/used up

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tissue stem cells: what can they do?

multi potent

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76

tissue stem cells: principles of renewing tissues

stem cell

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77

tissue stem cells: hematopoietic stem cells

found in the bone marrow & responsible for the continual production of blood cells

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78

tissue stem cells: neural stem cells

found in the nervous system, primarily in the brain & spinal cord, they are responsible for the continuous generation of new neurons

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79

tissue stem cells: gut stem cells

primarily located in the lining of the gastrointestinal tract, they play a vital role in maintaining & repairing the continuous cell turnover in the gut, as the gut lining is constantly exposed to mechanical & chemical stresses.

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80

tissue stem cells: mesenchymal stem cells

found in bone marrow, adipose (fat) tissue, and the stroma of many organs, they differentiate into bone cells (osteoblasts), cartilage cells (chondrocytes), & fat cells (adipocytes)f

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81

differences b/n embryonic & tissue stem cells

  1. different self

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82

niche

microenvironment around stem cells that provides support & signals regulating self

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83

iPS stem cells

type of pluripotent stem cell that can be generated directly from adult cells

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84

somatic cell nuclear transfer (SCNT)

method of reproductive cloning in which genetic material is transferred from an adult somatic cell into an unfertilized, enucleated egg

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iPS research

solution to the problems of immune rejection & use of human embryos to create new stem cell lines, shinya yamanaka

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86

what are iPSCs?

adult cells that have been genetically reprogrammed to an embryonic stem cell

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87

reversing cell differentiation advantages

introduce specific transcription factors (e.g., Oct4, Sox2, Klf4, and c

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88

role of 4 factors during reprogramming

oct3/4 & sox2

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89

retroviral transduction

any of a group of RNA viruses that insert a DNA copy of their genome into the host cell by a virus/viral vector in order to replicate

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90

immunocytochemistry

a method that involves fixing the cells, incubating them w/ antibodies specific to stem cell markers, & visualizing the expression of these markers through fluorescence microscopy to confirm their pluripotency

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91

microarray analysis

allows researchers to assess gene expression patterns of iPSCs

by comparing the transcriptome (the set of all expressed genes) of iPSCs to other cell types/developmental stages, scientists can identify genes that are specifically upregulated/downregulated in iPSCs

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92

activation of ES‐cell gene promoters

initiate and enhance gene transcription, maintaining the pluripotency of embryonic stem (ES) cells

luciferase reporter assay & chromatin immunoprecipitation

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93

telomerase activity & exponential growth

telomeres are protective caps at the ends of chromosomes, & they shorten w/ each cell division telomerase is an enzyme that can prevent/even reverse this shortening, ensuring that cells can divide repeatedly

in stem cells, telomerase activity is often high, allowing them to divide extensively & contribute to tissue repair & regeneration

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94

spontaneous differentiation (in vitro)

process by which undifferentiated/pluripotent stem cells undergo differentiation into more specialized cell types w/o the specific induction of differentiation factors/cues

this natural process occurs in cell culture conditions when stem cells are allowed to proliferate & mature over time

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95

directed differentiation to neural cells (in vitro)

process where stem cells/other precursor cells are manipulated to become specialized neural cells in a controlled laboratory setting

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96

teratoma

monster tumor, contains tissue from all 3 germ layers

allows us to determine if cells are pluripotent

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97

indirect lineage conversion

relies on the use of transcription factors associated w/ pluripotency

on forced expression, these factors first lead to removal of differentiate marks, creating an unstable state suitable for further differentiation on exposure to appropriate signals

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98

direct lineage conversion (transdifferentation)

lineage reprogramming, process where one mature somatic cell transforms into another mature somatic cell w/o undergoing an intermiediate pluripotent state/progenitor cell type

ex: neurons, cardiomyocytes

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99

Brn2, Ascl1, Myt1l

factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation

when combind w/ basic helix

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100

gene expressed in neural tissues

19, important roles in neural development/epigenetic reprogramming

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