Stem cell and its applicationsPresented by Khursheed ul islam

M.Phil First YearCIRBSc

Stem cells can be defined by two properties

Ability to make identical copies of themselves (self renewal)

During a stem cell division, one or both daughter cells maintain the stem cell phenotype . This process is called self-renewal.

The ability to form other cell types of the body

(differentiation).

What are stem cells?

Fig :- self renewal and differentiation of a stem cell.

Stem cells can be divided into two main groups:

Embryonic and adult or somatic stem cells. Embryonic stem cells are responsible for

embryonic and fetal development and growth. In the human body, adult stem cells are

responsible for growth, tissue maintenance and regeneration and repair of diseased or damaged tissue.

Types of stem cells

Embryonic stem cells: Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro—in an in vitro fertilization clinic—and then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman's body

culture of embryonic stem cells

Adult stem cells An adult stem cell is thought to be

an undifferentiated cell, found among differentiated cells in a tissue or organ.

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

Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis.

Induced pluripotent stem cells (iPSCs) are adult

cells that have been genetically reprogrammed to an embryonic stem cell–like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells

Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007.

1978: Stem cells were discovered in human cord blood.

In 2005 Scientists at Kingston university England found stem cells in umbilical cord blood.

The idea that stem cells are located in specific anatomical locations in adult tissue called ‘ niches ’ was introduced in 1978 by Schofield (1978) .

The niche is the stem cell microenvironment that provides a sheltering environment for the stem cells, in which the balance between stem cell quiescence and activity is maintained.

During differentiation, stem cell self-renewal genes have to be silenced, and only the tissue-specific genes have to be transcribed.

How stem cells remain un differentiated among differentiated cells inside a tissue?

LIF( leukemia inhibitory factor) keeps the mouse embryonic stem cells undifferentiated in the culture but it is not the same for human embryonic stem cells.

BMP4 signaling is mediated via the activation of SMAD1. Nanog can interact with SMAD1, and thereby inhibits the actions of BMP.

BMPs are also involved in mesoderma differentiation.

The inactivation of the BMPs by Nanog can help in maintaining the undifferentiated state of ES cells as shown in figure below.

Shows the regulation of NANOG expression.

One of the master genes of mouse ES cell pluripotency is the transcription factor Nanog.

Nanog is named after Tir Na Nog, Land of Ever Young or Land of Eternal Youth in Irish mythology.

In vivo , Nanog is expressed in the morula. In the blastocyst stage, expression is limited to the inner cell mass (ICM).

In vitro , Nanog is enriched in undifferentiated ES cells, but is downregulated in differentiating ES cells and in adult tissues.

Nanog the master gene in stem cell development

The expression of Nanog is regulated by a number of transcription factors .

The most important are Oct4 and Sox2, which can bind to an Oct4/Sox2 motif in the Nanog promoter, thereby activating Nanog transcription.

FoxD3, a transcription factor, is highly expressed in ES cells and can bind to an enhancer in the Nanog promoter, thereby activating gene transcription.

To allow differentiation during embryonic development, Nanog must also be negatively regulated. The tumour suppressor p53 and Tcf3, a transcription factor in the Wnt pathway, are considered to be negative regulators of Nanog expression in ES cells.

Stem cells allow us to study how organisms grow and develop over time.

Stem cells can replace diseased or damaged cells that can not heal or renew themselves.

We can test different substances (drugs and chemicals) on stem cells.

We can get a better understanding of our “genetic machinery.” Stem Cell Therapy has the Potential to:• Regenerate tissues/organs• Cure diseases like diabetes, multiple sclerosis, etc.

Stem cell field is still in its infancy. Human embryonic stem cell research is a decade old, adult

stem cell research has 30-year head start. Holds hope for curing or improving treatments for 70+

diseases.

Importance of stem cell research.

Generation of an iPS cell line from bone marrow derived mesenchymal stromal cells from an elderly patient.(Matthias et al, Stem Cell Research 15 (2015) 565–568).

Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells (Sou Nakamura et al, 2014 ,Cell Stem Cell).

Matthis et al, conformed that MSC-iPSC(74) can develop in all the three germ layers ,they also conformed the pluripotency by embryoid body based in vitro test.

Current work on stem cells.

Nakamura et al, showed that, when expressed at an appropriate level, c-MYC acts as a growth mediator in normal megakaryopoiesis and thrombopoiesis from hESCs or hiPSCs.

Excessive c-MYC expression in hematopoietic progenitor cells (HPCs) induces the activation of the INK4A and ARF path ways, leading to senescence and apoptosis.

C-MYC is a regulator gene that codes for a transcription factor. Protein encoded by this gene is a multifunctional ,nuclear phosphoprotein that plays a role in cell cycle progression , appoptosis and cellular transformation.

human induced pluripotent stem cells (hiPSCs)could represent a potent alternative source of platelet production

PRO CHOICE PEOPLE

“Utilitarianism – destruction of smaller group for the sake of large group.

Lead to significant information about the cause, new treatment possibilities, and potential cure for many deadly diseases.

Controversies in Stem cell research.

Stem cells are taken from a human blastocyst, which is then destroyed that amounts to “murder”.

There is a risk of commercial exploitation of the human participants in ESCR.

Stem cell research devalues life. Going against God.

Opinions against the stem cell research.

Adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for more than 40 years.

Umbilical cord containing stem cells can b collected at the time of birth and can be used to create stem cell bank that can be used in future

Applications

Therapeutic applications:1.Source:Current : Future: - Bone marrow – ES cells – Peripheral blood – iPS cells – Cord blood - Adipose tissue – Other2.Application:

• Current– Bone marrow transplantation– tissue engineering

• Future– Myocardial infarction and heart failure – CNS disease (incl. spinal cord injury)– Diabetes (beta-cells)-Parkinson’s Disease.– Other

Future role of stem cells.

Umbilical cord

Bone marrow