L1 - Introduction to Cell Biology

to understand the tissues and organisms that cells compose in details,
to determine what is “normal” so we can fix the “abnormal”,
to understand how macromolecular systems and organelles work and cooperate to enable cells to function autonomously and in tissues.

the cell is a fundamental unit of life, the basic building blocks of all living things,
the human body is composed of ~75 trillions of cells,

the technique used to grow cells or tissues outside the organism under strictly controlled conditions,
- cells are isolated from any tissue by breaking down the cell-cell and cell-matrix interactions by $mechanical fermentation$ , ==trypsin==, $EDTA$ .

@@Mechanical fragmentation@@
- breaks @@tissue@@ into smaller portions
@@Trypsin@@
- breaks down outer layer of @@proteins@@ that sticks cells together
@@EDTA@@
- an ion chelator that chelates to calcium and magnesium
- @@Integrin@@ sticks cells togethers, needs calcium to be stickier
- Magnesium and calcium also inhibit trypsin
cells in the cell culture: are supplied with proper nutrients (amino acids, minerals, vitamins, salts, glucose, etc.), serum (insulin, growth factors) and grown usually $at 37 C in a CO2 incubator.$
- @@CO2@@
- creates an acid-base equilibrium within the media
- $Yellow$ media
- overgrowth and lactic acid production
- ^^Purple^^ media
- lack of CO2 leading to an alkaline media
Cells can grow as: $adherent cell cultures$ or %%suspension cell cultures%%.

cells taken directly from an organism,
usually divide a limited number of times ( $\~50 generations, Hayflick limit$ ),
undergo contact inhibition if cell density is high.

the first human cell line established in 1952 by George Get (Johns Hopkins University, Baltimore) from cervical carcinoma biopsy of Henrietta Lacks.
Morphology of normal vs transformed fibroblasts
- Normal cells have a Hayflick limit, transformed cells don't

the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome before dividing,
both symmetric and asymmetric cell division occurs during development and in adult stem cells.

stem or progenitor cell generates,
a $copy of itself$ , which $retains self-renewal ability and differentiation potential,$
and %%one daughter that enters the path of differentiation,%%
==or two differently differentiated daughters.==

stem cell can divide into progenitor cells that are an intermediary,
can divide symmetrically,
differentiated cell can no longer be further modified,
a biological cell that can differentiate into a specific cell type,
more specific than stem cells, can only differentiate into their "target" cell type.

can be maintained in culture and can form differentiated cell types,
are pluripotent and can be grown indefinitely in culture under appropriate conditions,
can also be induced to differentiate into precursors for various cell types.
- Cells that survive in the feeder environment maintain the pluripotent property,
- can grow into embryo bodies in suspension culture to grow into tissues (germ layers) \n

can form organoids in culture,
- stem cells possess the intrinsic program to divide, differentiate, and organize themselves into complex structures.
- $Organoids$ :
- brain organoids have organization and structure remarkably similar to the fetal brain, but ==never== to the organization of adult brain
- organoids advance to fetal development state, but do not proceed to the organization seen in an adult organ.

contained by most tissues,
required to maintain and repair tissues,
capable of generating a limited number of different cell types,
located in $stem - cell niche,$
- (Replace the intestinal epithelium every 5 days!).
- intestinal stem cells are in the crypts (between villi)
- tops of the villi will die and peel off, the lower parts get pushed up from the crypt

an area of a tissue in which stem cells are present in an undifferentiated and self-renewable state,
- adjacent cells interact with the stem cells to signal $self renewal$ or %%differentiation%%.
- found in all parts of body
- efficient when young, starts to fail to regenerate or response to signal as one ages

obtain pluripotent cells from differentiated normal cells with Yamanaka factors.

three genes ( $*Oct4*$ , %%Sox2%%, ==Klf4==) and one frequently expressed in cancer cells (^^c-Myc^^).

inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell.
potentially cancerous, not safe for therapeutic use

derived from skin or blood cells reprogrammed back into an embryonic-like pluripotent state,
enables the development of an unlimited source of any type of human cell needed for therapeutic purposes.

mass production of affected cells for screening compounds and identifying the mutated genes
genetically modification to repair mutation and grow into new organ with in vitro differentiation for transplantations
- repopulate the brain, with healthy neurons for Parkinson’s disease
- Custom made, patient’s immune system will not reject the healthy cells

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