Stem Cells

Blok V

Cell characteristics

Growth potent Can be

Isolated Grew-up cell division, differentiating Embedded United hybrid

Stem cell

Stem cells are primal cells common to all multi-cellular organisms that retain the ability to renew themselves through cell division and can differentiate into a wide range of specialized cell types. The human stem cell field research findings by Canadian scientists Ernest A. McCulloch and James E. Till in the 1960s.

Pict. Mouse embryonic stem cells with fluorescent marker

Week 1:
2 cell stage Day 2
4 cell stage Late Day 2 Morula Day 3

Blastocyst Day 5

Fertilization Day 1

Implantation Day 6 - 7

In a developing embryo,
stem cells are able to differentiate into all of the specialized embryonic tissues.

In adult organisms,
stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells.

As stem cells can be readily grown and transformed into specialised cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture, their use in medical therapies has been proposed.

In particular, embryonic cell lines, autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates.

Pict. Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.

Totipotent stem cells can differentiate into any cell type in the body plus the placenta, which nourishes the embryo.
A fertilized egg is a type of totipotent stem cell. Cells produced in the first few divisions of the fertilized egg are also totipotent.

Pluripotent stem cells are descendants of the totipotent stem cells of the embryo.
These cells, which develop about four days after fertilization, can differentiate into any cell type, except for totipotent stem cells and the cells of the placenta.

Multipotent stem cells are descendents of pluripotent stem cells and antecedents of specialized cells in particular tissues, ex. :
Hematopoietic stem cells, which are found primarily in the bone marrow, give rise to all of the cells found in the blood, including red blood cells, white blood cells, and platelets. neural stem cells, which can differentiate into nerve cells and neural support cells called glia.

Progenitor cells (or unipotent stem cells) can produce only one cell type.
For example, erythroid progenitor cells differentiate into only red blood cells.

Stem cell division and differentiation.

A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation

The three broad categories of mammalian stem cells exist:

1. embryonic stem cells, derived from blastocysts, 2. adult stem cells, which are found in adult tissues, 3. cord blood stem cells, which are found in the umbilical cord.

Embryonic stem cells (ESCs)

Derived from 4- to 5-day-old embryos are known as blastocysts spherical Each blastocyst consists of 50 to 150 cells and includes three structures:
1. an outer layer of cells, 2. a fluid-filled cavity, and 3. a group of about 30 pluripotent cells at one end of the cavity called the inner cell mass, form all the cells of the body.

Embryonic stem cells (ESCs)

ESC cultures are created in the laboratory by transferring the inner cell mass from a blastocyst into a specially treated plastic culture dish. The cells divide and, after several days, begin to crowd the culture dish. When this happens, the cells are removed and plated into several fresh culture dishes.

Embryonic stem cells (ESCs)

This process is repeated many times, eventually yielding millions of ESCs. If, after six months, the cells keep dividing without differentiating, are still pluripotent, and are genetically normal, they are referred to as an ESC line

Embryonic stem cells (ESCs)

The blastocysts used for creating ESC lines are derived from eggs that were fertilized in in vitro fertilization clinics but never implanted in a womans uterus. The resulting embryos were frozen and later donated for research purposes with the informed consent of the donors. Currently, there are over 400,000 unused frozen embryos in U.S. fertility clinics.

Embryonic stem cells (ESCs)

ESCs must first be directed to differentiate into the desired cells, such as heart muscle cells, blood cells, or nerve cells. To control ESC differentiation in cell cultures, scientists try different techniques, such as
changing the chemical composition of the culture medium, altering the surface of the culture dish, or inserting specific genes into the cells.

Embryonic stem cells (ESCs)

One possible drawback to using differentiated ESC lines in stem cell therapies is that ESCs from one person might illicit an immune response when placed into another person,
because the proteins on the ESC surfaces might be viewed as foreign by the recipients immune system.

Embryonic stem cells (ESCs)

ESC derivatives have been transplanted between species (for example, pigs to rats) without being rejected, so the possibility exists that ESC derivatives from one person might be safely transplanted into another person. Studies investigating this have yet to be done.

Adult stem cells

Undifferentiated cells that are found in small numbers in most adult tissues. Also found in children and can be extracted from umbilical cord blood. A more accurate phrase is somatic stem cells, although this phrase has yet to be generally adopted.

Adult stem cells

The primary roles of adult stem cells in the body are to maintain and repair the tissues in which they are found. Usually thought of as multipotent cells, giving rise to a closely related family of cells within the tissue. An example is hematopoietic stem cells, which form all the various cells in the blood.

Adult stem cells

Some adult stem cell types may be pluripotent, or at least able to differentiate into multiple cell types. For example, hematopoietic stem cells can differentiate into neurons, glia, skeletal muscle cells, heart muscle cells, and liver cells. Whether they actually do this ordinarily within the body is unknown.

Adult stem cells

Blood from the placenta and umbilical cord that are left over after birth is a rich source of hematopoietic stem cells. So-called umbilical cord stem cells have been shown to be able to differentiate into bone cells and neurons, as well as the cells lining the inside of blood vessels.

Adult stem cells

Potential advantage of using adult stem cells from a patient is that

the patients own cells could be expanded in culture, treated to differentiate into the desired cells, and then reintroduced into the patient.

The use of the patients own cells would eliminate any possibility that they might be rejected by the immune system.

Adult stem cells

Disadvantages of using adult stem cells are that they are rare in mature tissues and it is more difficult to expand their numbers in cell culture, compared with ESCs

Embryonic (or fetal) germ cells

Pluripotent stem cells derived from so-called primordial germ cells, which are the cells that give rise to the gametes (sperm and eggs) in adults. Primordial germ cells from the area in a 5to 9-week-old embryo/fetus destined to become either the testicles or the ovaries (the dividing line between embryo and fetus is the end of the 8th week).

Embryonic (or fetal) germ cells

Like ESCs, the primordial germ cells are transferred into a specially treated plastic culture dish, where they form germ cell colonies. Less research has been performed using embryonic germ (EG) cells than ESCs, mostly because the embryos used for deriving EG cells are deliberately aborted, while the blastocysts used for deriving ESCs are produced through in vitro fertilization in a fertility clinic.

Embryonic (or fetal) germ cells

EG cells are also difficult to maintain in cell culture because they have a tendency to differentiate spontaneously.

Embryonic stem cell

(pluripotent)

Pluripotent

Stem cells are primitive cells that give rise to other types of cells. Also called progenitor cells, there are several kinds of stem cells. Totipotent cells are considered the "master" cells of the body because they contain all the genetic information needed to create all the cells of the body plus the placenta, which nourishes the human embryo.

Pluripotent

Human cells have this capacity only during the first few divisions of a fertilized egg. After 3 - 4 divisions of totipotent cells, there follows a series of stages in which the cells become increasingly specialized.

Pluripotent

The next stage of division results in pluripotent cells, which are highly versatile and can give rise to any cell type except the cells of the placenta or other supporting tissues for the uterus. Pluripotent At the next stage, cells become multipotent, meaning they can give rise to several other cell types, but those types are limited in number.

Pluripotent

An example of multipotent cells is hematopoietic cellsblood stem cells that can develop into several types of blood cells, but cannot develop into brain cells. At the end of the long chain of cell divisions that make up the embryo are "terminally differentiated" cellscells that are considered to be permanently committed to a specific function.

Multipotent

Multipotent stem cells can give rise to several other cell types, but those types are limited in number. An example of multipotent cells is hematopoietic cellsblood stem cells that can develop into several types of blood cells, but cannot develop into brain cells.

Multipotent

At the end of the long chain of cell divisions that make up the embryo are "terminally differentiated" cellscells that are considered to be permanently committed to a specific function. Scientists have long held the opinion that differentiated cells cannot be altered or caused to behave in any way other than the way in which they have been naturally committed.

Multipotent

New research, however, has even called that assumption into question. In recent stem cell experiments, scientists have been able to persuade blood stem cells to behave like neurons, or brain cells.

Multipotent

Scientists now believe that stem cell research could reveal far more vital information about our bodies than was previously known. There is also continuing research to see if it is possible to make multipotent cells into pluripotent types.

Embryonic vs adult stem cells

ES cells come from ICM of blastocyst

ES cells are pluripotent AS cells found in small amounts throughout body Most AS cells appear to be multipotent

Reproduced by permission of the NIH

Sources of ES cells

ES cell lines Excess embryos from IVF (in vitro fertilization) clinics Embryos created for research by IVF Therapeutic cloning

Reproduced by permission of the NIH

A primer on Human Embryonic Stem Cells Blastocyst from In Vitro Fertilization Clinic

Inner Cell Mass (Stem Cells)

Blueprint cells

A Blastocyst is a hollow ball of cells with a small clump of stem cells inside

Blastocyst from In Vitro Fertilization Clinic

Human Embryonic Stem Cells

Pipette

Stem Cells

Blueprint cells

A Blastocyst is a hollow ball of cells with a small clump of stem cells inside

Stem Cells

Blueprint cells

To remove the stem cells, the Blastocyst is opened and the stem cells removed with a pipette

Human Embryonic Stem Cells

Blastocyst from In Vitro Fertilization Clinic

Pipette

Stem Cells

Blueprint cells

Stem Cells

Blueprint cells

Stem Cells

A Blastocyst is a hollow ball of cells with a small clump of stem cells inside

To remove the stem cells, the Blastocyst is broken open and the stem cells removed with a pipette(an ultra thin glass tube)

The stem cells are placed in a dish and are fed and cared for (each blastocyst = 1 stem cell line)

Pipette

Petri Dish

Growth factors

Chemical cues

Stem Cells

Petri Dish

Pancreatic Islet Neuron

Muscle cell

Different chemicals / molecules are added to the stem cells to make them become specific types of cells.

Donor Egg

Somatic Cell Nuclear Transfer or Therapeutic Cloning

Skin Cell Nucleus (DNA) Needle Nucleus (DNA) Needle

Chemicals and Growth Factors

Stem Cells

Pancreatic Islet

Dividing cells

Stem Cells

Blastocyst

Neuron Muscle cell

To make stem cells into nerve cells

Blastocyst Pipette Blueprint cells

Stem Cells

Stem Cells

Petri Dish
Blueprint cells Stem Cells

The stem cells are treated with factors to cause them to differentiate into particular cell types

Stem cells differentiated into neurons

Stem Cell Therapy

CELL THERAPY is administration of cell suspensions containing stem cells that: Remain to live there;

Allocate in tissues and organs;

Produce generations of new cells ;

Restore functional activity of tissues and organs.

Stem cell therapy today

Treatment of diseases of aging:

Alzheimers disease Parkinsons disease Heat disease (replace cell lost to heart attack) Immune cancers:

Acute Myelogenous Leukemia Irradiation followed by bone marrow transplant.

Current Clinical Uses of Adult Stem Cells

CancersLymphomas, multiple myeloma, leukemias, breast cancer, neuroblastoma, renal cell carcinoma, ovarian cancer Autoimmune diseasesmultiple sclerosis, systemic lupus, rheumatoid, arthritis, scleroderma, scleromyxedema, Crohns disease Anemias (incl. sickle cell anemia) Immunodeficienciesincluding human gene therapy Bone/cartilage deformitieschildren with osteogenesis imperfecta Corneal scarring-generation of new corneas to restore sight Strokeneural cell implants in clinical trials Repairing cardiac tissue after heart attackbone marrow or muscle stem cells from patient Parkinsonsretinal stem cells, patients own neural stem cells, injected growth factors Growth of new blood vesselse.g., preventing gangrene Gastrointestinal epitheliaregenerate damaged ulcerous tissue Skingrafts grown from hair follicle stem cells, after plucking a few hairs from patient Wound healingbone marrow stem cells stimulated skin healing Spinal cord injuryclinical trials currently in Portugal, Italy, S. Korea.

Why all the fuss?

Stem cells may be able to replace damaged cells in the body Today: lymphoma, leukemia Future? Parkinsons, Alzheimers, diabetes... Promising animal studies

Courtesy of The Michael J. Fox Foundation for Parkinsons Research

Reproduced by permission of The Providence Journal

Ethical debate

Harvesting ES cells destroys the blastocyst This is murder

Reproduced by permission of Dave Catrow and Copley News Service

Ethical debate, contd

Courtesy of Kevin Siers, The Charlotte Observer 2001

ES cell research requires human cells Could create a commercial market for human cells This devalues life

Ethical debate, contd

If excess IVF embryos are being discarded anyway, they should be put to good use

Reprinted by permission of Chip Bok and Creators Syndicate, Inc.