tissue engineering 1

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

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

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

nsf

building blocks of tissue

basic unit of function in the body

groups of cells make & secrete their own support structures

also acts as a relay station for various signaling molecules

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

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

cells of donor organ are stripped and remaining collagen is used

have been implanted but procedures are still experimental & very costly

heart, lung, liver tissue

useful in research, in drug development

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

pigs intestine

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

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

1. autologous

2. allogeneic

3. syngeneic

4. xenogeneic

5. stem & progenitor

6. genetically engineered

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

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

transgenic studies, gene knockout studies, generation of chimeric animals

derived stem cell therapy

to treat dry AMD

1. angiogenic factors

2. growth factors

3. differentiation factors

4. transcription factors

5. bone morphogenic proteins

ex

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

ex

1. 2d cell expansion/scale

new imaging tools for real

funded researchers developing?

funded researchers projects? (6)

artificial skin & cartilage

1. robert langer

technique used to make many copies of a selected DNA sequence

a recording of the electrical activity of the heart

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

seq gene expression study

seq)

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

1. cells

2. tissues

3. homeostasis

4. signaling

5. ecm

6. biomaterials

1. microscopy

2. bioimaging

3. pcr

4. dna sequencing

5. gene expression profiling

6. gene delviery/therapy

7. bioMEMS

8. nanotechnology

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

high

time constant analysis, scale

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

based approach using 3d

healthy donor tissue/organ

inner lining membrane of the uterus

collagen i & matrigel cell

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

1. biomaterial fabrication

2. cell isolation & expansion

3. cell seeding

4. scaffold conditioning

5. implantation

tissue engineered endometrium

tissue engineered endometrium

1. extrusion bio printing

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

1. biomaterials

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

integra life sciences corp lifecell corp

on market

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

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

designed to enable rapid & continuous expression of smn protein

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

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

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

removing tissue from animals from transplantation into a human

• available supply, standardized products

artificial heart, heart valves, prosthetic hips, etc.

• fill short term needs

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

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

renew & differentiate?

embryonic stem cells (blastocyst

isolated from very young mammalian embryos blastocyst

pluripotent

tumorigenicity immune rejection genomic stability limited sources heterogeneity

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

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

multi potent

stem cell

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

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

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.

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

1. different self

microenvironment around stem cells that provides support & signals regulating self

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

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

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

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

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

oct3/4 & sox2

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

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

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

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

luciferase reporter assay & chromatin immunoprecipitation

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

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

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

monster tumor, contains tissue from all 3 germ layers

allows us to determine if cells are pluripotent

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

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

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

when combind w/ basic helix

19, important roles in neural development/epigenetic reprogramming