Stem Cells - Term Paper

8/6/2019 Stem Cells - Term Paper

1/34

Submitted toSubmitted toSubmitted toSubmitted to---- Submitted by Submitted by Submitted by Submitted by---- Ankmani Shrivastava Ankmani Shrivastava Ankmani Shrivastava Ankmani Shrivastava B.tech Biotechnology B.tech Biotechnology B.tech Biotechnology B.tech Biotechnology SEM SEM SEM SEM 3 33 3 rd rd rd rd


2/34

2

INDEXINDEXINDEXINDEX SerialNo.

Topic PageNo.

1 Table of discussion

Introduction to Cell World History of Cell Introduction to Stem Cells Unique properties of Stem Cells Embryonic Stem Cells

Cell Culture

3-

3-4

5-7

8-11

12-12

12-15

2 Review

Adult Stem cells 3 Discussion and conclusion4 Bibliography. 5 Appendix


3/34

3

Introduction to Cell World Introduction to Cell World Introduction to Cell World Introduction to Cell World History of CellHistory of CellHistory of CellHistory of Cell

"Cells are the unit of structure, function, and reproduction in lThat's probably the definition but complicated.

Lets have a look on this simpler definition: "Anything that's alof cells."

Every organism that you can think whether it be an octopus oror an ant, is made of cells.

Humans are made of literally billions of cells. According to calculationaverage human body consists of 100 trillion cells.

They are so small that they can only be seen under a microscocarry oxygen in our blood, some produce sweat, and some allowhether it's hot or cold.

Although most organisms are made of many different types of some organisms are just one, single cell. Biologists call this tyof organismunicellular .

The study of cells is known ascytologycytologycytologycytology . Cytology began in 1665, when RHooke, an English scientist, first glimpsed into the microscopiexamining dead cork cells under a primitive microscope which


4/34

4

1. During the next 170 years most important discovery came up in 1838, when a German botanist named Matthias Schleiden suggested that all plant tissues are made of cells.

2. Just one year later, zoologist Theodore Schwann made a simanimals.

3. In 1858, Rudolf Virchow suggested that all cells come from

The ideas of these three scientists created the cell thcell thcell thcell theoryeoryeoryeory. The three main aspthe theory are:

1. Anything that is living is composed of c2. The chemical reactions that occur in an o

in cells.3. All cells come from preexisting cells.

An amoeba(image courtesy of BIODIDAC)

Matthias Schleiden(image courtesy of Encylopd

Britannica)

Rudolf Virchow (image courtesyof EncylopdiaBritannica)


5/34

5

I II Introducntroducntroducntroductiontiontiontion to stem cellsto stem cellsto stem cellsto stem cellsThere are some special kinds of cells which have capability to specialized in the organ system, coined as Stem Cells.

Stem cells have the remarkable potential to develop into manytypes in the body during early life and growth.

They also serve as a sort of internal repair system in tissue, divwithout limit to replenish other cells as long as the person or a

After division, each new stem cell has the potential either to re

cell or become another type of cell with a more specialized funmuscle cell, red blood cell, or brain cell.

Stem cells are distinguished from other cell types by two impocharacteristics.

1- Unspecialized Unspecialized Unspecialized Unspecialized cellscellscellscells capable of renewing themselves through cell(sometimes after long periods of inactivity.)

2- Under certain physiologic or experimental conditions, they become tissue, organ or specific cells with special functions. Ias gut and bone marrow, stem cells regularly divide to repair aout or damaged tissues. In other organs such as the pancreas a stem cells only divide under special conditions.

Until recently, scientists primarily worked with two kinds of sanimals and humans:-

1. Embryonic stem cells and 2. Non-Embryonic "somatic" or "adult" stem cells.


6/34

6

The functions and characteristics of these cells will be explainScientists discovered ways to derive embryonic stem cells fromnearly 30 years ago, in 1981. The detailed study of the biologythe discovery, in 1998, of a method to derive stem cells from hthe cells in the laboratory. These cells are called human embryhuman embryonic stem chuman embryonic stem chuman embryonic stem c

The embryos used in these studies were created for reproductiinininvitrofert vitrofert vitrofert vitrofertilizationilizationilizationilization procedures.

When they were no longer needed for that purpose, they were research with the informed consent of the donor. In 2006, reseanother breakthrough by identifying conditions that would allo

specialized adult cells to be "reprogrammed" genetically to aslike state. This new type of stem cell, called induced pluripoteinduced pluripotent stem celinduced pluripotent stem celinduced pluripotent stem cel(iPSCs)(iPSCs)(iPSCs)(iPSCs), will be discussed in a later section of this document.

Stem cells are important for living organisms for many reasons. In the 3-embryo, called a blastocyst, the inner cells give rise to the entire body ofincluding all of the many specialized cell types and organs such as the he sperm, eggs, red blood corpses and other tissues.

In some adult tissues such as bone marrow, muscle, brain etc, discrete po stem cells generate replacements for cells that are lost through normal w


7/34

7

injury or disease. The unique regenerative abilities of stem cells offer netreating diseases such as diabetes and heart disease. Nowa-days they hausing them in treatment of damages made in retina, making up for damagetc, also. However, much work remains to be done in the lab and the clinuse of these cells for cell-based therapies to treat disease, which is also ras regenerative or reparative medicine. Laboratory studies of stem cells elearn about the cells essential properties and what makes them differentcell types. Scientists are already using stem cells in the lab to screen newdevelop model systems to study normal growth and identify the causes o Research on stem cells continues to advance knowledge about how an ora single cell and how healthy cells replace damaged cells in adult organis

Stem cell research is one of the most fascinating areas of contemporary bmany expanding fields of scientific inquiry, research on stem cells raisesas rapidly as it generates new discoveries.

Photo courtesy University of Wisconsin


8/34

8

Unique properties of stem cellsStem cells differ from other kinds of cells in the body. All stemtheir source and have three general properties:-

1. They are capable of dividing and renewing themselves for l they are unspecialized; and they can give rise to specialized ce

2. Stem cells are capable of dividing and renewing themselves periods. Unlike muscle cells, blood cells, or nerve cells (which normally replicate themselves) stem cells may replicate many or proliferate.

3. A starting population of stem cells that proliferates for many the laboratory can yield millions of cells. If the resulting cells c be unspecialized, like the parent stem cells, the cells are said to of long long long long----term self term self term self term self----renewal renewal renewal renewal. .. .

Scientists are trying to understand two fundamental propertiesthat relate to their long-term self-renewal:1. Why can embryonic stem cellsembryonic stem cellsembryonic stem cellsembryonic stem cells proliferate for a year or more inwithout differentiating, but most nonnonnonnon----embryonic stem cellsembryonic stem cellsembryonic stem cellsembryonic stem cells cannot? an

2. What are the factors in living organisms that normally regu proliferation and self-renewal?

Discovering the answers to these questions may make it possibhow cell proliferation is regulated during normal embryonic dduring the abnormal cell division that leads to cancer. Such infwould also enable scientists to grow embryonic and non-embrmore efficiently in the laboratory.


9/34

9

The specific factors and conditions that allow stem cells to remunspecialized are of great interest to scientists. It has taken sciyears of trial and error to learn to derive and maintain stem cellaboratory without them spontaneously differentiating into spetypes. For example, it took two decades to learn how to grow hhuman embryonihuman embryonihuman embryoni stem cells stem cells stem cells stem cells in the laboratory following the development of conmouse stem cells. Therefore, understanding the signals in a mathat cause a stem cell population to proliferate and remain unsuntil the cells are needed.Such information is critical for scientists toto grow large numbers of unspecialized stem cells in the labor experimentation.

Research going on for Human Embryonic Stem Cell ResearchLaboratory in Ann Arbor, Mich.

Stem cells are unspecialized Stem cells are unspecialized Stem cells are unspecialized Stem cells are unspecialized. One of the fundamental propertithat it does not have any tissue-specific structures that allow it specialized functions. For example, a stem cell cannot work wto pump blood through the body (like a heart muscle cell), andoxygen molecules through the bloodstream (like a red blood c


10/34

10

unspecialized stem cells can give rise to specialized cells, inclmuscle cells, blood cells, or nerve cells.Stem cells can give rise to specialized cells. When unspecializrise to specialized cells, the process is called differentiationdifferentiationdifferentiationdifferentiation.

While differentiating, the cell usually goes through several stamore specialized at each step. Scientists are just beginning to u signals inside and outside cells that trigger each stem of the di process.

The internal signals are controlled by a cell's genes, which areacross long strands of DNA, and carry coded instructions for a

structures and functions. The external signals for cell differentchemicals secreted by other cells, physical contact with neighbcertain molecules in the microenvironment microenvironment microenvironment microenvironment. The interaction of signadifferentiation causes the cell's DNA to acquire epigeneticepigeneticepigeneticepigenetic marks that restric DNA expression in the cell and can be passed on through cell Many questions about stem cell differentiation remain. For exainternal and external signals for cell differentiation similar for stem cells? Can specific sets of signals be identified that prominto specific cell types? Addressing these questions may lead snew ways to control stem cell differentiation in the laboratory,growing cells or tissues that can be used for specific purposes cellcellcell----based based based based therapiestherapiestherapiestherapies or drug screening.


11/34

11

The second phase of a clinical trial testing on a new stem-cell-based.

RNL launches the world's first human stem cell based cosmetics.

Adult stem cells typically generate the cell types of the tissue reside. For example, a blood-forming adult stem cell in the bonormally gives rise to the many types of blood cells. It is genethat a blood-forming cell in the bone marrowwhich is calledhematopoietihematopoietihematopoieti stem cell stem cell stem cell stem cellcannot give rise to the cells of a very different tissucells in the brain. Experiments over the last several years have show that stem cells from one tissue may give rise to cell typedifferent tissue. This remains an area of great debate within thcommunity. This controversy demonstrates the challenges of s stem cells and suggests that additional research using adult stenecessary to understand their full potential as future therapies.


12/34

12

EMBRYONIC STEM CELLS Embryonic ste Embryonic ste Embryonic ste Embryonic stem cellsm cellsm cellsm cells, as their name suggests, are derived from emembryonic stem cells are derived from embryos that develop f

been fertilized in vitroin an in vitro fertilization clinicand for research purposes with informed consent of the donors. Th from eggs fertilized in a woman's body. The embryos from whembryonic stem cells are derived are typically four or five dayhollow microscopic ball of cells called the blastocyst. The blasthree structures: the trophoblast, which is the layer of cells thathe blastocoel, a hollow cavity inside the blastocyst; and the in

which is a group of cells at one end of the blastocoel that deveembryo proper.

Cell cultureCell cultureCell cultureCell cultureGrowing cells in the laboratory is known as cell culture. Huma

stem cells are isolated by transferring the inner cell mass into laboratory culture dish that contains a nutrient broth known asmedium. The cells divide and spread over the surface of the di surface of the culture dish is typically coated with mouse embthat have been treated so they will not divide. This coating laycalled a feeder layer.

The mouse cells in the bottom of the culture dish provide the cells a sticky surface to which they can attach. Also, the feedenutrients into the culture medium. Researchers have devised wembryonic stem cells without mouse feeder cells. This is a sigadvance because of the risk that viruses or other macromolecucells may be transmitted to the human cells. The process of ge


13/34

13

embryonic stem cell line is somewhat inefficient, so lines are ntime an inner cell mass is placed into a culture dish. However,inner cell mass cells survive, divide and multiply enough to crthey are removed gently and plated into several fresh culture d process of re-plating or sub culturing the cells is repeated manmany months.

Each cycle of sub culturing the cells is referred to as a passageline is established, the original cells yield millions of embryon Embryonic stem cells that have proliferated in cell culture for months without differentiating are pluripotent pluripotent pluripotent pluripotent stem cells. stem cells. stem cells. stem cells.

Pluripotent-These type of cells are specialized in over 200 types of different types oThis can be given with an example The second stage of an embryo where after 3 to 5 days it is specializedcells of different kinds and help out in bringing out an individual this sta blastocyst(duration5 to 14 days).

And appear genetically normal are referred to as an embryonicembryonicembryonicembryonic stem cell li stem cell line stem cell line stem cell line. At any stage in the process, batches of cells can be frozen andlaboratories for further culture and experimentation.

At various points during the process of generating embryonic scientists test the cells to see whether they exhibit the fundamthat make them embryonic stem cells. This process is called chScientists who study human embryonic stem cells have not ye standard battery of tests that measure the cells' fundamental prHowever, laboratories that grow human embryonic stem cell l kinds of tests, including:


14/34

14

1. Growing and sub culturing the stem cells for many months.the cells are capable of long-term growth and self-renewal. Scthe cultures through a microscope to see that the cells look heaundifferentiated.

2. Using specific techniques to determine the presence of tranthat are typically produced by undifferentiated cells.

Two of the most important transcription factors are Nanog andTranscriptions factors help turn genes on and off at the right tiimportant part of the processes of cell differentiation and embrdevelopment. In this case, both Oct 4 and Nanog are associate

maintaining the stem cells in an undifferentiated state, capablerenewal.

1. Using specific techniques to determine the presence of partimarkers that are typically produced by undifferentiated cells.

2. Examining the chromosomes under a microscope. This is a whether the chromosomes are damaged or if the number of chchanged. It does not detect genetic mutations in the cells.

Determining whether the cells can be re-grown, or subculture,thawing, and re-plating.

Testing whether the human embryonic stem cells are pluripote

1) Allowing the cells to differentiate spontaneously in cell cu 2) Manipulating the cells so they will differentiate to form celcharacteristic of the three germ layers; or

3) Injecting the cells into a mouse with a suppressed immune the formation of a benign tumor called a teratomateratomateratomateratoma.


15/34

15

Since the mouses immune system is suppressed, the injected hare not rejected by the mouse immune system and scientists caand differentiation of the human stem cells. Teratomas typicalmixture of many differentiated or partly differentiated cell typindications that the embryonic stem cells are capable of differemultiple cell types.


16/34

16

SSSStem cell differentiationtem cell differentiationtem cell differentiationtem cell differentiation

Figure 1.Directed differentiation of mouse embryonic stem cells.(2001 Terese Winslow)

As long as the embryonic stem cells in culture are grown undeconditions, they can remain undifferentiated (unspecialized). Ballowed to clump together to form embryoid bodiesembryoid bodiesembryoid bodiesembryoid bodies, they begin to diffe spontaneously. They can form muscle cells, nerve cells, and m. They can form muscle cells, nerve cells, and many. They can form muscle cells, nerve cells, and many. They can form muscle cells, nerve cells, and manytypetypetypetypes ss s.


17/34

17

Although spontaneous differentiation is a good indication thatembryonic stem cells is healthy, it is not an efficient way to prof specific cell types.So, to generate cultures of specific types of differentiated cellscells, blood cells, or nerve cells, for examplescientists try todifferentiation of embryonic stem cells. They change the chemof the culture medium, alter the surface of the culture dish, or by inserting specific genes. Through years of experimentationestablished some basic protocols or "recipes" for the directed dembryonic stem cells into some specific cell types (Figure 1).(For additional

examples of directed differentiation of embryonic stem cells, r stem cell reports available at /info/2006report/ /info/2006report/ /info/2006report/ /info/2006report/ and /info/2001report/2001report.htm /info/2001report/2001report.htm /info/2001report/2001report.htm /info/2001report/2001report.htm.)

If scientists can reliably direct the differentiation of embryonic stem cinto specific cell types, they may be able to use the resulting, differencells to treat certain diseases in the future. Diseases that might be treatransplanting cells generated from human embryonic stem cells include Parkinson's disease , diabetes, traumatic spinal cord injury , Duchenne's muscular dystrophy , heart disease, and vision and hearing loss.
http://www.ninds.nih.gov/disorders/md/md.htmhttp://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htm


18/34

18

REVIEW REVIEW REVIEW REVIEW Some thing about Adult Stem cellSome thing about Adult Stem cellSome thing about Adult Stem cellSome thing about Adult Stem cells ss s

An adult stem cell is thought to be an undifferentiated cell, foudifferentiated cells in a tissue or organ that can renew itself andifferentiate to yield some or all of the major specialized cell tor organ.

The primary roles of adult stem cells in a living organism are t

repair the tissue in which they are found.Scientists also use the term somatic stem cell instead of adult s somatic refers to cells of the body (not the germ cells, sperm o

Unlike embryonic stem cells, which are defined by their origininner cellinner cellinner cellmassmassmassmass of the blastocyst blastocyst blastocyst blastocyst), the origin of adult stem cells in some mat still under investigation.

Research on adult stem cells has generated a great deal of excScientists have found adult stem cells in many more tissues ththought possible. This finding has led researchers and clinicianadult stem cells could be used for transplants. In fact, adult hem blood-forming, stem cells from bone marrow have been used 40 years. Scientists now have evidence that stem cells exist in the heart. If the differentiation of adult stem cells can be contrlaboratory, these cells may become the basis of transplantationtherapies.

The history of research on adult stem cells began about 50 yea


19/34

19

In the 1950s, researchers discovered that the bone marrow con kinds of stem cells. One population, called hematopoietic stemhematopoietic stem cellhematopoietic stem cellhematopoietic stem cells ss s, forms allthe types of blood cells in the body. A second population, calle bone marrow bone marrow bone marrow stromal stem cells stromal stem cells stromal stem cells stromal stem cells (also called mesencmesencmesencmesenchymal stem cellshymal stem cellshymal stem cellshymal stem cells, or skeletal stem some), were discovered a few years later. These non-hematopmake up a small proportion of the stromal cell population in thand can generate bone, cartilage, fat, cells that support the formand fibrous connective tissue.

In the 1960s, scientists who were studying rats discovered twothat contained dividing cells that ultimately become nerve cellreports, most scientists believed that the adult brain could not nerve cells. It was not until the 1990s that scientists agreed tha brain does contain stem cells that are able to generate the braincell typesastrocytesastrocytesastrocytesastrocytes andoligodendrocytesandoligodendrocytesandoligodendrocytesandoligodendrocytes, which are non-neuronaand neurons, or nerve cells.


20/34

20

Site of adult stem cells and their function- Adult stem cells have been identified in many organs and tissu brain, bone marrow, peripheral blood, blood vessels, skeletal mheart, gut, liver, ovarian epithelium, and testis. They are thouga specific area of each tissue (called a "stem cell niche"). In mcurrent evidence suggests that some types of stem cells are percompose the outermost layer of small blood vessels. Stem cellquiescent (non-dividing) for long periods of time until they arenormal need for more cells to maintain tissues, or by disease o

Typically, there is a very small number of stem cells in each tiremoved from the body, their capacity to divide is limited, maof large quantities of stem cells difficult. Scientists in many latrying to find better ways to grow large quantities of adult stemcellcellcellcultureculturecultureculture and to manipulate them to generate specific cell types used to treat injury or disease. Some examples of potential trearegenerating bone using cells derived from bone marrow strominsulin-producing cells for type-

1. Diabetes, and

2. Repairing damaged heart muscle following a heart attack wmuscle cells.


21/34

21

SomeSomeSomeSome tests are used f tests are used f tests are used f tests are used for identifying adult stemor identifying adult stem celor identifying adult stem celor identifying adult stem celthey are as follows:they are as follows:they are as follows:they are as follows:----Scientists often use one or more of the following methods to idcells:-

(1) Label the cells in a living tissue with molecular markers andetermine the specialized cell types they generate.

(2) Remove the cells from a living animal, label them in cell ctransplant them back into another animal to determine whethereplace (or "repopulate") their tissue of origin.Importantly, it must be demonstrated that a single adult stem cgenerate a line of genetically identical cells that then gives riseappropriate differentiated cell types of the tissue. To confirm ethat a putative adult stem cell is indeed a stem cell, scientists teither that the cell can give rise to these genetically identical cand/or that a purified population of these candidate stem cells or reform the tissue after transplant into an animal.


22/34

22

C. A C. A C. A C. Adult stem cell differentiationdult stem cell differentiationdult stem cell differentiationdult stem cell differentiation----

Figure 2.

Hematopoietic and stromal stem cell differentiation.( 2001 Terese Winslow)

As indicated above, scientists have reported that adult stem cemany tissues and that they enter normal differentiation pathwathe specialized cell types of the tissue in which they reside.

Normal differentiation pathways of adult stem cells. In a livingadult stem cells are available to divide, when needed, and can mature cell types that have characteristic shapes and specializeand functions of a particular tissue.

The following are examples of differentiation pathways of adu(Figure 2) that have been demonstrated in vitroin vitroin vitroin vitro or or or or in vivo.in vivo.in vivo.in vivo.


23/34

23

Hematopoietic stem cells give rise to all the types of blood cellymphocytes, T lymphocytes, natural killer cells, neutrophils, eosinophils, monocytes, and macrophages.

Mesenchymal stem cells give rise to a variety of cell types: bo(osteocytes), cartilage cells (chondrocytes), fat cells (adipocyt kinds of connective tissue cells such as those in tendons.

Neural stem cellsNeural stem cellsNeural stem cellsNeural stem cells in the brain give rise to its three major cell ty(neurons) and two categories of non-neuronal cellsastrocyteoligodendrocytesoligodendrocytesoligodendrocytesoligodendrocytes.

Epithelial stem cells in the lining of the digestive tract occur inand give rise to several cell types: absorptive cells, goblet cellenteroendocrine cells.

Skin stem cells occur in the basal layer of the epidermis and at follicles. The epidermal stem cells give rise to keratinocytes, wthe surface of the skin and form a protective layer. The follicucan give rise to both the hair follicle and to the epidermis.

TransdifferentiationTransdifferentiationTransdifferentiationTransdifferentiation---- A number of experiments have reported that certain adult stemdifferentiate into cell types seen in organs or tissues other than from the cells' predicted lineage (i.e., brain stem cells that diff blood cells or blood-forming cells that differentiate into cardiaand so forth). This reported phenomenon is called transdifferetransdifferentiationtransdifferentiationtransdifferentiation.

Although isolated instances of transdifferentiation have been overtebrate species, whether this phenomenon actually occurs iunder debate by the scientific community. Instead of transdiffeobserved instances may involve fusion of a donor cell with a r Another possibility is that transplanted stem cells are secreting


24/34

24

encourage the recipient's own stem cells to begin the repair prtransdifferentiation has been detected, only a very small perceundergo the process.

In a variation of transdifferentiation experiments, scientists hademonstrated that certain adult cell types can be other cell types in vivo using a well-controlled process of gene(see Section VI for a discussion of the principles of reprogram

This strategy may offer a way to reprogram available cells intothat have been lost or damaged due to disease. For example, oexperiment shows how pancreatic beta cells, the insulin-produare lost or damaged in diabetes, could possibly be created by rother pancreatic cells. By "re-starting" expression of three critgenes in differentiated adult pancreatic exocrine cells, researchcreate beta cell-like cells that can secrete insulin. The reprogra similar to beta cells in appearance, size, and shape; expressed characteristic of beta cells; and were able to partially restore b

regulation in mice whose own beta cells had been chemically not transdifferentiation by definition, this method for reprogracells may be used as a model for directly reprogramming othe

In addition to reprogramming cells to become a specific cell ty possible to reprogram adult somatic cells to become like embr(induced pluripotent stem cells, iPSCs)(induced pluripotent stem cells, iPSCs)(induced pluripotent stem cells, iPSCs)(induced pluripotent stem cells, iPSCs) through the introductiogenes. Thus, a source of cells can be generated that are specifithereby avoiding issues of histocompatibility, if such cells wertissue regeneration. However, like embryonic stem cells, determethods by which iPSCs can be completely and reproducibly appropriate cell lineages is still under investigation.


25/34

25

Many important questions about adult stemMany important questions about adult stemMany important questions about adult stemMany important questions about adult stemremain to be answered. They include:remain to be answered. They include:remain to be answered. They include:remain to be answered. They include:----1. How many kinds of adult stem cells exist, and in which tiss

2. How do adult stem cells evolve during development and homaintained in the adult? Are they "leftover" embryonic stem carise in some other way?

3. Why do stem cells remain in an undifferentiated state whenaround them have differentiated? What are the characteristics

niche that controls their behavior? 4. Do adult stem cells have the capacity to transdifferentiate, ato control this process to improve its reliability and efficiency?

5. If the beneficial effect of adult stem cell transplantation is awhat are the mechanisms?

6. Is donor cell-recipient cell contact required, secretion of faccell, or both?

7. What are the factors that control adult stem cell proliferatiodifferentiation?

8. What are the factors that stimulate stem cells to relocate to sor damage, and how can this process be enhanced for better he


26/34

26

SSSSimilarities and differences betweenimilarities and differences betweenimilarities and differences betweenimilarities and differences between embembembembryonic and ryonic and ryonic and ryonic and adult stem cells areadult stem cells areadult stem cells areadult stem cells are::::----Human embryonicHuman embryonicHuman embryonicHuman embryonic and adult stem cellsadult stem cellsadult stem cellsadult stem cells each have advantages and disadvantages regarding potential use for cellcellcellcell----based regenerative therapie based regenerative therapie based regenerative therapie based regenerative therapiemajor difference between adult and embryonic stem cells is thabilities in the number and type of differentiated cell types the become. Embryonic stem cells Embryonic stem cells Embryonic stem cells Embryonic stem cells can become all cell types of the bare pluripotent pluripotent pluripotent pluripotent.

Adult stem cells are thought to be limited to differentiating int

types of their tissue of origin. Embryonic stem cells can be grown relatively easily in culturecells are rare in mature tissues, so isolating these cells from anchallenging, and methods to expand their numbers in cell cultucell culturecell culturecell culture have not y been worked out. This is an important distinction, as large numneeded for stem cell replacement therapies.

Scientists believe that tissues derived from embryonic and adudiffer in the likelihood of being rejected after transplantation. know whether tissues derived from embryonic stem cells woutransplant rejection, sincethe first phase 1 clinical trial testing the safety ocells derived from hESCS has only recently been approved byFood and Drug Administration (FDA).

Adult stem cells, and tissues derived from them, are currently likely to initiate rejection after transplantation. This is becauseown cells could be expanded in culture, coaxed into assumingtype (differentiation), and then reintroduced into the patient. Tadult stem cells and tissues derived from the patient's own adu


27/34

27

would mean that the cells are less likely to be rejected by the iThis represents a significant advantage, as immune rejection ccircumvented only by continuous administration of immunosuand the drugs themselves may cause deleterious side effects

Lets understand w Lets understand w Lets understand w Lets understand what hat hat hat induced pluripotent stem induced pluripotent stem induced pluripotent stem induced pluripotent stem are:are:are:are:----Induced pluripotent stem cells (iPSCs)Induced pluripotent stem cells (iPSCs)Induced pluripotent stem cells (iPSCs)Induced pluripotent stem cells (iPSCs) are adult cells that havegenetically reprogrammed to an embryonic stem celllike stat

to express genes and factors important for maintaining the defof embryonic stem cells. Although these cells meet the definin pluripotent stem cells, it is not known if iPSCs and embryonicin clinically significant ways. Mouse iPSCs were first reportedhuman iPSCs were first reported in late 2007. Mouse iPSCs deimportant characteristics of pluripotent stem cells, including ecell markers, forming tumors containing cells from all three ge being able to contribute to many different tissues when injecteembryos at a very early stage in development. Human iPSCs acell markers and are capable of generating cells characteristic layers.

Although additional research is needed, iPSCs are already usedevelopment and modeling of diseases, and scientists hope to

transplantation medicine. Viruses are currently used to introdureprogramming factors into adult cells, and this process must bcontrolled and tested before the technique can lead to useful trhumans. In animal studies, the virus used to introduce the stem sometimes causes cancers. Researchers are currently investigadelivery strategies. In any case, this breakthrough discovery ha


28/34

28

powerful new way to "de-differentiate" cells whose developm been previously assumed to be determined. In addition, tissueiPSCs will be a nearly identical match to the cell donor and thavoid rejection by the immune system. The iPSC strategy crea stem cells that, together with studies of other types of pluripotwill help researchers learn how to reprogram cells to repair dathe human body.

P PP Potentialotentialotentialotential uses of human stem cells and the ouses of human stem cells and the obuses of human stem cells and the obuses of human stem cells and the obthat must be overcome before thesethat must be overcome before thesethat must be overcome before thesethat must be overcome before these potentia potential uses wi potential uses wi potential uses wi be realized be realized be realized be realized There are many ways in which human stem cells can be used ithe clinic. Studies of human embryonic stem cells will yield inabout the complex events that occur during human developmegoal of this work is to identify how undifferentiated stem cellsdifferentiated cells that form the tissues and organs. Scientists turning genes on and off is central to this process. Some of themedical conditions, such as cancer and birth defects, are due tdivision and differentiation.

A more complete understanding of the genetic and molecular processes may yield information about how such diseases aris strategies for therapy. Predictably controlling cell proliferationdifferentiation requires additional basic research on the molecu signals that regulate cell division and specialization. While recdevelopments with iPS cells suggest some of the specific factoinvolved, techniques must be devised to introduce these factorcells and control the processes that are induced by these factor


29/34

29

Human stem cells could also be used to test new drugs. For exmedications could be tested for safety on differentiated cells ghuman pluripotent cell lines. Other kinds of cell lines are alreaway. Cancer cell lines, for example, are used to screen potentidrugs. The availability of pluripotent stem cells would allow dwider range of cell types.

However, to screen drugs effectively, the conditions must be idcomparing different drugs. Therefore, scientists will have to bcontrol the differentiation of stem cells into the specific cell tydrugs will be tested. Current knowledge of the signals controlldifferentiation falls short of being able to mimic these conditiogenerate pure populations of differentiated cells for each drug Perhaps the most important potential application of human stegeneration of cells and tissues that could be used for cell-baseddonated organs and tissues are often used to replace ailing or d but the need for transplantable tissues and organs far outweigh supply. Stem cells, directed to differentiate into specific cell ty possibility of a renewable source of replacement cells and tissincluding Alzheimer's diseases, spinal cord injury, stroke, burndiabetes, osteoarthritis, and rheumatoid arthritis.


30/34

30

Figure 3.

Strategies to repair heart muscle with aduladuladuladult stem cellst stem cellst stem cellst stem cells.(2001 Terese Winslow)

For example, it may become possible to generate healthy hearthe laboratory and then transplant those cells into patients withheart disease. Preliminary research in mice and other animals bone marrow stromal cells, transplanted into a damaged heart, beneficial effects. Whether these cells can generate heart musc stimulate the growth of new blood vessels that repopulate the help via some other mechanism is actively under investigationinjected cells may accomplish repair by secreting growth factoactually incorporating into the heart. Promising results from anhave served as the basis for a small number of exploratory stu(for discussion, see call-out box, "Can Stem Cells Mend a BroOther recent studies in cell culture stems indicate that it may bdirect the differentiation of embryonic stem cells or adult boneinto heart muscle cells (Figure 3)


31/34

31

A really interesting question is whether a st A really interesting question is whether a st A really interesting question is whether a st A really interesting question is whether a stcan repair a broken heart? can repair a broken heart? can repair a broken heart? can repair a broken heart? Stem Cells for the Future Treatment of Heart DiseaseCardiovascular disease (CVD), which includes hypertension, cdisease, stroke, and congestive heart failure, has ranked as the cause of death in the United States every year since 1900 excenation struggled with an influenza epidemic. Nearly 2600 AmCVD each day, roughly one person every 34 seconds. Given th population and the relatively dramatic recent increases in the pcardiovascular risk factors such as obesity and type 2 diabetes significant health concern well into the 21st century.

Cardiovascular disease can deprive heart tissue of oxygen, thecardiac muscle cells (cardiomyocytes). This loss triggers a casdetrimental events, including formation of scar tissue, an over flow and pressure capacity, the overstretching of viable cardiaattempting to sustain cardiac output, leading to heart failure, adeath. Restoring damaged heart muscle tissue, through repair ois therefore a potentially new strategy to treat heart failure.The use of embryonic and adult-derived stem cells for cardiacactive area of research. A number of stem cell types, including(ES) cells, cardiac stem cells that naturally reside within the hmyoblasts (muscle stem cells), adult bone marrow-derived celmesenchymal cells (bone marrow-derived cells that give rise tmuscle, bone, tendons, ligaments, and adipose tissue), endothecells (cells that give rise to the endothelium, the interior liningvessels), and umbilical cord blood cells, have been investigate sources for regenerating damaged heart tissue. All have been eor rat models, and some have been tested in larger animal mod


32/34

32

A few small studies have also been carried out in humans, usuwho are undergoing open-heart surgery. Several of these have that stem cells that are injected into the circulation or directly injured heart tissue appear to improve cardiac function and/or formation of new capillaries. The mechanism for this repair recontroversial, and the stem cells likely regenerate heart tissue pathways. However, the stem cell populations that have been texperiments vary widely, as do the conditions of their purificaapplication. Although much more research is needed to assessimprove the efficacy of this approach, these preliminary clinic show how stem cells may one day be used to repair damaged h

thereby reducing the burden of cardiovascular disease.In people who suffer from type 1 diabetes, the cells of the pannormally produce insulin are destroyed by the patient's own imNew studies indicate that it may be possible to direct the differhuman embryonic stem cells in cell culture to form insulin-prothat eventually could be used in transplantation therapy for perdiabetes.

To realize the promise of novel cell-based therapies for such pdebilitating diseases, scientists must be able to manipulate stemthey possess the necessary characteristics for successful differtransplantation, and engraftment. The following is a list of stepcell-based treatments that scientists will have to learn to controtreatments to the clinic.

To be useful for transplant purposes, stem cells must be reprod1. Proliferate extensively and generate sufficient quantities of

2. Differentiate into the desired cell type(s).

3. Survive in the recipient after transplant.


33/34

33

4. Integrate into the surrounding tissue after transplant.

5. Function appropriately for the duration of the recipient's life

6. Avoid harming the recipient in any way.

Also, to avoid the problem of immune rejection, scientists are with different research strategies to generate tissues that will n

To summarize, stem cells offer exciting promise for future the significant technical hurdles remain that will only be overcomof intensive research.

We can get more information from the giveWe can get more information from the giveWe can get more information from the giveWe can get more information from the givelinkslinkslinkslinks----For a more detailed discussion of stem cells, see the NIH's SteNIH's Stem Cell ReportsNIH's Stem Cell ReportsNIH's Stem Cell ReportsCheck the Frequentlythe Frequentlythe Frequentlythe Frequently Asked Questions Asked Questions Asked Questions Asked Questions page for quick answers to squeries. The navigation table at right can connect you to the inneed.

The following websites, which are not part of the NIH Stem C site, also contain information about stem cells. The NIH is notthe content of these sites.1.1.1.1. http://www.isscr.org/publichttp://www.isscr.org/publichttp://www.isscr.org/publichttp://www.isscr.org/public

Stem cell information for the public from the International SocCell Research (ISSCR).

2. 2. 2. 2. http://www.nlm.nih.gov/medlineplus/stemcells.html
http://www.nlm.nih.gov/medlineplus/stemcells.htmlhttp://www.nlm.nih.gov/medlineplus/stemcells.htmlhttp://www.nlm.nih.gov/medlineplus/stemcells.html


34/34

Medline Plus is a consumer health database that includes newsresources, clinical trials, and more

3. 3. 3. 3. http://www.explorestemcells.co.ukhttp://www.explorestemcells.co.ukhttp://www.explorestemcells.co.ukhttp://www.explorestemcells.co.uk

A United Kingdom-based resource for the general public that stem cells in medical treatments and therapies.

4.4.4.4. http://www.stemcellresearchnews.comhttp://www.stemcellresearchnews.comhttp://www.stemcellresearchnews.comhttp://www.stemcellresearchnews.com

A huge source of knowledge is

5. http://www.britannica.com

6.http://www.wikipedia.com

7. http://www.World bookonline.com
http://www.britannica.com/http://www.britannica.com/http://www.wikipedia.com/http://www.wikipedia.com/http://www.wikipedia.com/http://www.britannica.com/

Documents

Stem Cells - Term Paper