Stem cell research

Topic: Advances In Stem Cell Topic: Advances In Stem Cell Research Research

Submitted By: M.Z.Arifeen.Submitted By: M.Z.Arifeen.

Submitted To: Dr. Aftab Ali ShahSubmitted To: Dr. Aftab Ali Shah

Student Of: M.Phil in Biotecnology Student Of: M.Phil in Biotecnology University of Malakand University of Malakand

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INTRODUCTION OF STEM INTRODUCTION OF STEM CELL TECHNOLOGYCELL TECHNOLOGY

Stem Cell – DefinitionStem Cell – Definition

• A cell that has the ability to A cell that has the ability to continuously divide and differentiate continuously divide and differentiate (develop) into various other kind(s) of (develop) into various other kind(s) of cells/tissues cells/tissues

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Stem Cell CharacteristicsStem Cell Characteristics

‘‘Blank cells’ (unspecialized)Blank cells’ (unspecialized) Capable of dividing and renewing Capable of dividing and renewing

themselves for long periods of time themselves for long periods of time (proliferation and renewal)(proliferation and renewal)

Have the potential to give rise to Have the potential to give rise to specialized cell types (differentiation)specialized cell types (differentiation)

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Kinds of Stem CellsKinds of Stem Cells

Stem cell Stem cell typetype DescriptionDescription ExamplesExamples

TotipotentTotipotent Each cell can develop Each cell can develop into a new individualinto a new individual

Cells from early (1-Cells from early (1-3 days) embryos3 days) embryos

PluripotentPluripotent Cells can form any (over Cells can form any (over 200) cell types200) cell types

Some cells of Some cells of blastocyst (5 to 14 blastocyst (5 to 14 days)days)

MultipotentMultipotent

Cells differentiated, but Cells differentiated, but can form a number of can form a number of other tissues other tissues cells can differentiate into a number of cells, but only those of a closely related family of cells

Fetal tissue, cord Fetal tissue, cord blood, and adult blood, and adult stem cellsstem cells

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Oligopotent: stem cells can differentiate into only a few : stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cellscells, such as lymphoid or myeloid stem cells

Unipotent cells can produce only one cell type, their  cells can produce only one cell type, their own,own, but have the property of self-renewal, which but have the property of self-renewal, which distinguishes them from non-stem cells (e.g., muscle distinguishes them from non-stem cells (e.g., muscle stem cells).stem cells).

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Stem Cell DifferentiationStem Cell Differentiation

Princeton University

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This cellThis cellCan form the Can form the

Embryo and placentaEmbryo and placenta

This cellThis cellCan just form theCan just form the

embryoembryo

Fully mature Fully mature 99

Kinds of Stem CellsKinds of Stem Cells

Embryonic stem cells come from a five to six-day-old embryo. They have the ability to form virtually any type of cell found in the human body.

Embryonic germ cells are derived from the part of a human embryo or foetus that will ultimately produce eggs or sperm (gametes).

Adult stem cells are undifferentiated cells found among specialised or differentiated cells in a tissue or organ after birth. Based on current research they appear to have a more restricted ability to produce different cell types and to self-renew.

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Blastocyst DiagramBlastocyst Diagram

Princeton University

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Sexual ReproductionSexual Reproduction

The Association of Reproductive Health Professionals

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Stages of EmbryogenesisStages of Embryogenesis

Day 1Fertilized egg

Day 1Fertilized egg

Day 22-cell embryo

Day 22-cell embryo Day 3-4

Multi-cell embryoDay 3-4

Multi-cell embryo

Day 5-6BlastocystDay 5-6

BlastocystDay 11-14Tissue Differentiation

Day 11-14Tissue Differentiation 1414

Derivation and Use of Derivation and Use of Embryonic Stem Cell LinesEmbryonic Stem Cell Lines

Isolate inner cell mass(destroys embryo)

Isolate inner cell mass(destroys embryo)

Heart muscleKidney

“Special sauce”(largely unknown)

Day 5-6BlastocystDay 5-6

Blastocyst

Inner cells(forms fetus)Inner cells

(forms fetus)

Outer cells(forms placenta)

Outer cells(forms placenta)

Heartrepaired

Culture cellsCulture cells

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Stages of EmbryogenesisStages of Embryogenesis

blastocystblastocyst Blastocyst inner mass cellsBlastocyst inner mass cells

8-cell stage8-cell stagecleavagecleavage

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An adult stem cell is thought to be an An adult stem cell is thought to be an undifferentiatedundifferentiated cell,  cell, found among differentiated cells in a tissue or organ that can renew found among differentiated cells in a tissue or organ that can renew itself and can differentiate to yield some or all of the major itself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ.specialized cell types of the tissue or organ.

The primary roles of The primary roles of adult stem cellsadult stem cells in a living organism are to  in a living organism are to maintain and repair the tissue in which they are found.maintain and repair the tissue in which they are found.

Scientists also use the term Scientists also use the term somatic stem cellsomatic stem cell instead of adult  instead of adult stem cell, where somatic refers to cells of the body (not the germ stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs).cells, sperm or eggs).

What are adult stem cells?What are adult stem cells?

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If the differentiation of adult stem cells can be controlled in the If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-laboratory, these cells may become the basis of transplantation-based therapies.based therapies.

The history of research on adult stem cells began about 60 years The history of research on adult stem cells began about 60 years ago. In the 1950s, researchers discovered that the bone marrow ago. In the 1950s, researchers discovered that the bone marrow contains at least two kinds of stem cells. contains at least two kinds of stem cells. 

1.1.One population, called One population, called hematopoietic stem cellshematopoietic stem cells, forms all the , forms all the types of blood cells in the body.types of blood cells in the body.2.2.A second population, called A second population, called bone marrow stromal stem bone marrow stromal stem cellscells (skeletal stem cells), These non-hematopoietic stem cells  (skeletal stem cells), These non-hematopoietic stem cells make up a small proportion of the make up a small proportion of the stromal cellstromal cell population in the  population in the bone marrow, and can generate bone, cartilage, fat, cells that bone marrow, and can generate bone, cartilage, fat, cells that support the formation of blood, and fibrous connective tissue.support the formation of blood, and fibrous connective tissue.

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Where are adult stem cells found, and Where are adult stem cells found, and what do they normally do?what do they normally do?

Adult stem cells have been identified in many organs and tissues, Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis.and testis.They are thought to reside in a specific area of each tissue They are thought to reside in a specific area of each tissue called a "stem cell niche.called a "stem cell niche.

Stem cells remain non-dividing for long periods of time until Stem cells remain non-dividing for long periods of time until they are activated by a normal need for more cells to maintain they are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury.tissues, or by disease or tissue injury.

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Typically, there is a very small number of stem cells in each Typically, there is a very small number of stem cells in each tissue, and once removed from the body, their capacity to divide is tissue, and once removed from the body, their capacity to divide is limited, making generation of large quantities of stem cells limited, making generation of large quantities of stem cells difficult.difficult.

Scientists in many laboratories are trying to find better ways to Scientists in many laboratories are trying to find better ways to grow large quantities of adult stem cells in grow large quantities of adult stem cells in cell culturecell culture and to  and to manipulate them to generate specific cell types so they can be used manipulate them to generate specific cell types so they can be used to treat injury or disease.to treat injury or disease.

Some examples of potential treatments include regenerating Some examples of potential treatments include regenerating bone using cells derived from bone marrow stroma, developing bone using cells derived from bone marrow stroma, developing insulin-producing cells for type 1 diabetes, and repairing damaged insulin-producing cells for type 1 diabetes, and repairing damaged heart muscle following a heart attack with cardiac muscle cells.heart muscle following a heart attack with cardiac muscle cells.

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AdultAdult stemstem cellscells

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scientists have reported that adult stem cells occur in many scientists have reported that adult stem cells occur in many tissues and that they enter normal tissues and that they enter normal differentiationdifferentiation pathways to  pathways to form the specialized cell types of the tissue in which they reside.form the specialized cell types of the tissue in which they reside.

Normal differentiation pathways of adult stem cells:Normal differentiation pathways of adult stem cells:

In a living animal, adult stem cells are available to divide, In a living animal, adult stem cells are available to divide, when needed, and can give rise to mature cell types that have when needed, and can give rise to mature cell types that have characteristic shapes and specialized structures and functions of characteristic shapes and specialized structures and functions of a particular tissue. a particular tissue.

The following are examples of differentiation pathways of The following are examples of differentiation pathways of adult stem cells that have been demonstrated adult stem cells that have been demonstrated in vitroin vitro or  or in vivoin vivo..

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

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

Neural stem cellsNeural stem cells in the brain give rise to its three major cell  in the brain give rise to its three major cell types: nerve cells (neurons) and two categories of non-neuronal types: nerve cells (neurons) and two categories of non-neuronal cells—astrocytes and oligodendrocytes.cells—astrocytes and oligodendrocytes.

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Epithelial stem cellsEpithelial stem cells in the lining of the digestive tract in the lining of the digestive tract occur in deep crypts and give rise to several cell types: occur in deep crypts and give rise to several cell types: absorptive cells, goblet cells, paneth cells, and enteroendocrine absorptive cells, goblet cells, paneth cells, and enteroendocrine cells.cells.Skin stem cellsSkin stem cells occur in the basal layer of the epidermis and occur in the basal layer of the epidermis and at the base of hair follicles. The epidermal stem cells give rise to at the base of hair follicles. The epidermal stem cells give rise to keratinocytes, which migrate to the surface of the skin and form keratinocytes, which migrate to the surface of the skin and form a protective layer. The follicular stem cells can give rise to both a protective layer. The follicular stem cells can give rise to both the hair follicle and to the epidermis.the hair follicle and to the epidermis.

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The Promise of Stem CellsThe Promise of Stem Cellspotential application of stem cells is making cells and tissues for potential application of stem cells is making cells and tissues for medical therapiesmedical therapies

Today, donated organs and tissues are often used to replace Today, donated organs and tissues are often used to replace those that are diseased or destroyedthose that are diseased or destroyed

Unfortunately, the number of people needing a transplant far Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantationexceeds the number of organs available for transplantation

Pluripotent stem cells offer the possibility of a renewable Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat diseases, source of replacement cells and tissues to treat diseases, conditions, and disabilities including Parkinson's disease, conditions, and disabilities including Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heart amyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes, and arthritis.disease, diabetes, and arthritis.

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ApplicationsApplications

Disease• Diabetes, Spinal

cord injury, Parkinson’s disease, heart disease

Genetic based Disease

• Cystic fibrosis, Huntington’s

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Somatic Stem Cell Therapy: Using a Bone Marrow Somatic Stem Cell Therapy: Using a Bone Marrow Transplant to Cure LeukemiaTransplant to Cure Leukemia

Leukemia is a cancer of white blood cells, or leukocytes.Leukemia is a cancer of white blood cells, or leukocytes.

Like other blood cells, leukocytes develop from somatic stem Like other blood cells, leukocytes develop from somatic stem cells. Mature leukocytes are released into the bloodstream, where cells. Mature leukocytes are released into the bloodstream, where they work to fight off infections in our bodies.they work to fight off infections in our bodies.

Leukemia results when leukocytes begin to grow and function Leukemia results when leukocytes begin to grow and function abnormally, becoming cancerousabnormally, becoming cancerous

Successful treatment for leukemia depends on getting rid of all Successful treatment for leukemia depends on getting rid of all the abnormal leukocytes in the patient, allowing healthy ones to the abnormal leukocytes in the patient, allowing healthy ones to grow in their place. One way to do this is through chemotherapy, grow in their place. One way to do this is through chemotherapy, which uses potent drugs to target and kill the abnormal cells. which uses potent drugs to target and kill the abnormal cells. When chemotherapy alone can't eliminate them all, physicians When chemotherapy alone can't eliminate them all, physicians sometimes turn to bone marrow transplants.sometimes turn to bone marrow transplants.

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In a bone marrow transplant, the patient's bone marrow stem In a bone marrow transplant, the patient's bone marrow stem cells are replaced with those from a healthy, matching donorcells are replaced with those from a healthy, matching donor

To do this, all of the patient's existing bone marrow and To do this, all of the patient's existing bone marrow and abnormal leukocytes are first killed using a combination of abnormal leukocytes are first killed using a combination of chemotherapy and radiation. chemotherapy and radiation. 

Next, a sample of donor bone marrow containing healthy stem Next, a sample of donor bone marrow containing healthy stem cells is introduced into the patient's bloodstream.cells is introduced into the patient's bloodstream.

If the transplant is successful, the stem cells will migrate into If the transplant is successful, the stem cells will migrate into the patient's bone marrow and begin producing new, healthy the patient's bone marrow and begin producing new, healthy leukocytes to replace the abnormal cells.leukocytes to replace the abnormal cells.

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Umbilical Cord Blood Stem CellsUmbilical Cord Blood Stem CellsNewborn infants no longer need their umbilical cords, so they Newborn infants no longer need their umbilical cords, so they have traditionally been discarded as a by-product of the birth have traditionally been discarded as a by-product of the birth process. In recent years, however, the stem-cell–rich blood found process. In recent years, however, the stem-cell–rich blood found in the umbilical cord has proven useful in treating the same types in the umbilical cord has proven useful in treating the same types of health problems as those treated using bone marrow stem cells of health problems as those treated using bone marrow stem cells and PBSCs.and PBSCs.

Umbilical cord blood stem cell transplants are less prone to Umbilical cord blood stem cell transplants are less prone to rejection than either bone marrow or peripheral blood stem cells. rejection than either bone marrow or peripheral blood stem cells. This is probably because the cells have not yet developed the This is probably because the cells have not yet developed the features that can be recognized and attacked by the recipient's features that can be recognized and attacked by the recipient's immune system. Also, because umbilical cord blood lacks well-immune system. Also, because umbilical cord blood lacks well-developed immune cells, there is less chance that the transplanted developed immune cells, there is less chance that the transplanted cells will attack the recipient's body,cells will attack the recipient's body,

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Unknowns in Stem Unknowns in Stem Cell/Cloning ResearchCell/Cloning Research

• It is uncertain that human It is uncertain that human embryonic stem cells embryonic stem cells in vitroin vitro can can give rise to all the different cell give rise to all the different cell types of the adult body.types of the adult body.

• It is unknown if stem cells cultured It is unknown if stem cells cultured in vitroin vitro (apart from the embryo) (apart from the embryo) will function as the cells do when will function as the cells do when they are part of the developing they are part of the developing embryoembryo

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Challenges to Stem Challenges to Stem Cell/Cloning ResearchCell/Cloning Research

• Stem cells need to be Stem cells need to be differentiated to the differentiated to the appropriate cell type(s) appropriate cell type(s) beforebefore they can be used they can be used clinically.clinically.

• Recently, abnormalities in Recently, abnormalities in chromosome number and chromosome number and structure were found in structure were found in three human ESC lines. three human ESC lines.

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Challenges to Stem Challenges to Stem Cell/Cloning ResearchCell/Cloning Research

• Stem cell development or proliferation Stem cell development or proliferation must be controlled once placed into must be controlled once placed into patients.patients.

• Possibility of rejection of stem cell Possibility of rejection of stem cell transplants as foreign tissues is very high.transplants as foreign tissues is very high.

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Challenges to Stem Challenges to Stem Cell/Cloning ResearchCell/Cloning Research

• Contamination by viruses, bacteria, fungi, Contamination by viruses, bacteria, fungi, and Mycoplasma possible.and Mycoplasma possible.

• The use of mouse “feeder” cells to grow The use of mouse “feeder” cells to grow ESC could result in problems due to ESC could result in problems due to xenotransplantation (complicating FDA xenotransplantation (complicating FDA requirements for clinical use).requirements for clinical use).

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(Time 2.19.01)

ThanksThanks

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In case of any In case of any question please question please contact me at contact me at [email protected][email protected]