Understanding Stem Cell

Abdurahman Laqif

Yuyun Rindiastuti

Department of Obstetrics and Gynecology Medical Faculty of Sebelas Maret University

Dr. Moewardi General Hospital of SurakartaIndonesia

Contents• What is Stem cell (SC)

– Definition– Microanatomy– Characteristics– Development phase of SC

• When– Stem cell time line

• Why– Plasticity/ differntiation

• Where– Resource– Work

• How – Make SC– Work in the tissue/ body

Definition

• Stem cells are unspecialized cells in the human body that are capable of becoming specialized cells, each with new specialized cell functions.

Definition

• Progenitor cell ( Precursor cell): is unspecialized or has partial characteristic of specialized cell that is capable of undergoing cell division and yielding two specialized cells 2-Example is the myeloid progenitor/precursor undergoing cell division to yield two specialized cells, a-A neutrophil b-A red blood cell

Progenitor SC

Intermediate/ progenitor stem cell• 1-Stem cells, in general, generate an

intermediate cell type or types before they achieve their final differentiation.

• 2-The intermediate cell is called a precursor or progenitor cell. 3-Progenitor or precursor cells in fetal or adult tissues are partly differentiated cells that divide and give rise to differentiated cells. 4-Such cells are usually regarded as "committed" to differentiate along a particular cellular developmental pathway

Stem cells and Progenitor cell

Microanatomy Image: Stem cell

Stem cell

stem cell colony

Characteristics

Stem cells have two important characteristics that distinguish them from other types of cells.

• First, they are unspecialized cells that renew themselves for long periods through cell division.

• The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as the beating cells of the heart muscle or the insulin producing cells of the pancreas

What is a Stem Cell?

Two identical daughters Self-renewal Differentiate

Somatic Cell Stem Cell

Properties of stem cell:

• they are:

1. capable of dividing and renewing themselves for long periods

2. they are unspecialized

3. and they can give rise to specialized cell types

Sources of stem cells:

• Embryonic Stem Cells• Adult Stem Cells

• Adult Stem Cells

• Adult Stem Cells

Sources of Embryonic Stem Cells

1. In Vitro Fertilization ( IVF) Blastocyst

2. Nuclear Transfer (SCNT)

A human blastocyst,which is producedabout 5 days afterfertilization, is smallerthan the period atthe end of this sentence.NIH/Mr. J.Conaghan.

Somatic Cell Nuclear Transfer

DOLLY

1997

“Decisions”not irreversible

Melissa Henriksen, PhD

Producing Embryonic Stem Cells Using Nuclear Transfer Is Not the Same as

Reproductive Cloning

The use of nuclear transfer to develop disease-specific stem cells can be called research cloning, and the use of this technique for personalized tissue transplants is sometimes called therapeutic cloning. These terms must be carefully distinguished from reproductive cloning, in which the intent is to implant a cloned embryo in a female’s womb and allow it to develop fully into an individual.

- Bone Marrow Stem Cells- Peripheral Blood Stem Cells- Neuronal Stem Cells (from olfactory bulb, spinal cord)

- Muscle Stem Cells- Liver Stem Cells- Pancreatic Stem Cells- Corneal Limbal Stem Cells- Umbilical Cord Blood

Adult Stem Cells sources

Human Stem Cell Classification based on the sources

SC classification based on differentiation potency

The range of commitment options available to a cell

• Totipotent

• Pluripotent

• Multipotent

• Oligopotent

• Unipotent

Potency

SC classification based on differentiation potency

• Totipotent Stem Cells: The master cells of the body that contain all the genetic information needed to create all the cells of the body and the placenta. Totipotent cells exist only in the first three to four divisions of the fertilized egg and give rise to the next stage of development — the pluripotent stem cells

• Pluripotent Stem Cells: Stem cells that can develop into all the different cell types in the body except the placenta. They give rise to mulitpotent and unipotent stem cells as the embryo develops.

• Multipotent Stem Cells: Stem cells that can give rise to a limited number of other cell types. They are committed to becoming a variety of cell types associated with specific functions or organs/tissues (e.g., blood, heart, muscle) in the body. For example, blood stem cells give rise to red blood cells, white blood cells, and platelets

• Unipotent Stem Cells: Stem cells that can renew and give rise to only a single mature cell type.

Potency

Pluripotent Multipotent

Different Cell Types

Same DNA Different Gene Expression

pancreatic bone neurons ES

Stem cell plasticity

Plasticity of HESC

• Human embryonic stem cell (HESC) telah terbukti sangat primitif, dapat berproliferasi tanpa batas, dan memiliki kemampuan untuk menurunkan galur semua jenis sel dewasa.

Plasticity of ASC

• adult stem cell (ASC), dari jaringan dewasa yang sudah terarah menjadi jaringan tertentu, masih mampu berdiferensiasi menjadi sel bagian dari suatu jaringan lain. Pada saat ini belum ada istilah baku untuk menyebut fenomena ini dalam literatur ilmiah. Maka sering disebut sebagai plastisitas, diferensiasi unorthodox, maupun transdiferensiasi.

• Tampaknya, dengan sinyal microenvironment, yang sesuai, adult stem cell dari sumsum tulang mampu bertransdiferensiasi menjadi berbagai macam sel dari organ yang berbeda-beda.

Kirschstein R, Skirboll LR.

• 1. It is the ability of an adult stem cell from one tissue to generate the cell type (s) of another tissue. 2. Example under experimental conditions, adult stem cells from bone marrow generated cells that resemble neurons and other cell types are found in the brain. 3. Evidence suggests that, adult stem cells are capable of being "genetically reprogrammed” to generate cells that have characteristics of different tissues.

Dr. Fakhri Al-Bagdadi BVSc, Ph.D.

Plasticity of ASC

Development phase of SC

• Tidak diketahui asal muasal yang pasti dari adult stemcell ; beberapa peneliti mengajukan hipotesis bahwa stem cell yang dicegah untuk berdiferensiasi ini disebar dan diletakkan dengan mekanisme tertentu yang belum diketahui selama periode perkembangan fetal.

Patterns of stem cell division: From SC to terminal diffferentiated cell

Why SC have plasticity capability?

• Kerusakan jaringan tampaknya menciptakan lingkungan yang sesuai bagi perubahan orientasi diferensiasi ini. Tampaknya lingkungan jaringan extrahematopoietic yang terbentuk setelah apoptosis atau nekrosis (seperti keseimbangan sitokin maupun keadaan matriks ekstraseluler) memungkinkan engraftment yang sesuai bagi stem cell yang sedang beredar di aliran darah. Yang tidak diketahui adalah apakah stem cell melewati fase jaringan spesifik sebelum maturasi, baik melalui transdiferensiasi maupun fusi sel.

Plastisitas: Transdiferensiasi langsung dan tak langsung

• Sel yang sudah terarah telah memulai rangkaian diferensiasi terminal yang diduga disebabkan oleh perubahan konformasi DNA. Transdiferensiasi menunjukkan kemampuan dari sebuah sel yang sudah terarah untuk mengubah pola ekspresi gennya menjadi sel yang betul betul berbeda dengan karakter asalnya, dan ini dapat terjadi langsung maupun tak langsung. Transdiferensiasi tak langsung berarti stem cell berde-diferensiasi diikuti proses maturasi ke jalur alternatif. Transdiferensiasi langsung berarti terdapat transisi langsung pada pola ekspresi gen sel tersebut.

Plastisitas : Fusi sel

• Mekanisme alternatif untuk plastisitas adalah terjadinya fusi sel antara hematopoietic stem cell dengan non-hematopoietic stem cell membentuk heterokarion, dengan demikian mengubah pola ekspresi gen dari pola asli sel sumsum tulang menjadi pola ekspresi pasangan fusinya. Contohnya, fusi in vitro fibroblast dengan myoblast diketahui menghasilkan ekspresi mRNA yang spesifik untuk myocyte dengan nuklei yang spesifik untuk fibroblast.

When ?

How : Stem cell work? Stem cell Niche

• Both ES cells and somatic stem cells are thought to be maintained (and perhaps defined) by the environment produced by the surrounding differentiated cells.

• • Exactly how this stem cell niche is maintained is not known yet.

• • The differentiated cells may:• – secret specific factors into the surrounding matrix• – communicate with the stem cells via gap junctions or receptor mediated

inducers• – Such communication may activate specific signaling pathways, such as the

Wnt/frizzled (which activates Lef-1/TCF), Notch/delta, or• Sonic hedgehog/patched pathways.

• • Loss of the stem cell niche can induce a stem cell to divide, die, or differentiate.

• • Change in the niche may induce a stem cell to alter its phenotype and its function.

Stem cell Niche

Use