Stem Cell Therapy


 


STEM CELLS: 

Stem cells are undifferentiated or partially differentiated cells in multicellular animals that can specialize into many types of cells and multiply endlessly to produce additional stem cells.

For purposes of tissue engineering and cell therapies, stem cells are usually obtained from four basic sources. The main sources are




1) embryonic tissue,

2) foetal tissues, such as foetus, placenta (i.e., amnion and chorion), amniotic fluid and umbilical cord (Wharton jelly, blood),

3) specific locations in the adult organism, e.g., fat, bone marrow, skeletal muscle, skin, or blood, and

4) differentiated somatic cells after they have been genetically reprogrammed.



Hierarchy of Cell potency: 

■ Totipotent Stem Cells: 

Stem cells can give rise to any of 220 cell types found in embryos as well as extra-embryonic cells(placenta).

■ pluripotent Stem Cells: 

can give rise to all cell types of body (but not the placenta).

■ Multipotent Stem Cells:

 can develop a limited number of cell types in a particular lineage.

■ Unipotent Stem Cells: give rise to cells of their own type along a single lineage .

Allogeneic Stem Cell:

Allogeneic stem cell transplantation involves transferring the stem cells from a healthy person (the donor) to the patient’s body after high-intensity chemotherapy or radiation. The donated stem cells can come from either a related or an unrelated donor.

■An allogeneic stem cell transplant is most often used to treat blood cancers, such as leukemia and lymphoma, and certain types of blood or immune system disorders.




Characteristics of Stem Cells:

■ Totiptency : generate all types of cells including germ cells.


.☆  Pluripotency:  generate all types of cells except cells of the embryonic membrane.

☆  Multipotency: differentiate into more than one mature cell. Self-renewal: divide without differentiation and create everlasting supply.

.☆  Plasticity: Multipotent stem cells have plasticity and can undergo differentiation.

■  The trigger for plasticity is stress or tissue injury which upregulates the stem cells and releases chemoattractants and growth factors. 


Stem cell therapy, also known as regenerative medicine, promotes the repair response of diseased, dysfunctional, or injured tissue using stem cells or their derivatives. 


■ Researchers grow stem cells in a lab. 


■ These stem cells are manipulated to specialize into specific types of cells, such as heart muscle cells, blood cells or nerve cells. 



■ The specialized cells can then be implanted into a person. 


■ For example, if the person has heart disease, the cells could be injected into the heart muscle.

■  The healthy transplanted heart muscle cells  could then contribute to repairing defective heart muscle .


Story of HeLA Cells: 

■ Henrietta Lacks, a Black woman, was a 31 _ year _ old mother of five when she died from cervical cancer in 1951.

■ Her name and memory live on in the form of a remarkable lineage of continually dividing cells that have achieved, to all intents and purposes, “immortality.”


 ■ Her cancer cells have continued to live well beyond her death in labs around the world, replicating so prolifically that laid end-to-end they could be wrapped around the earth three times. 

■ HeLa cells have since become the most widely used human cell line in biological research and were critical for many biomedical breakthroughs of the past half century. 

■ Jonas Salk, for instance, used them in 1954 to develop the polio vaccine and in the 1980s AIDS researchers used them to identify and isolate the human immunodeficiency virus (HIV) while in recent years HeLa cells were critical for the “omics” revolution, from genomics to transcriptomics and proteomics.






■Potential to Reverse Diseases: By directing stem cells to differentiate into specialised cell types, there is the possibility to provide a renewable source of replacement cells for those suffering from diseases.

 ■Minimal invasion: Stem cell therapy is a non-surgical procedure with no incisions of the body. Traditional surgeries leave behind scars that require extended time periods to heal.


 ■Faster recovery: Since the procedure is quick and minimally invasive, it requires very little to no time for the recovery process. One can get back to their routine work on the next day of the procedure. 


■Natural healing: The human body has the potential to heal by itself with the help of stem cell therapy. Once the stem cells are injected at the site of injury, they stimulate the growth of new cells, which repair and heal the damage tissue.


■ Prevents complications: Unlike most of the medical treatment, stem cell therapy comes with no side effects. It also prevents infections and reduces the risk of complications.

Genome Editing:

Genome editing, also known as genome Engineering or gene editing, is a sort of genetic engineering that involves inserting,deleting, modifying,or replacing DNA in a living organism's genome.

T_ (CAR_ T) THERAPY:


■ Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of a patient’s autologous T-cells to express a CAR specific for a tumour antigen.


■ It is followed by ex vivo cell expansion and re-infusion back to the patient. 


CARs are fusion proteins of a selected single-chain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signalling domains. 


■This T-cell genetic modification may occur either via viral-based gene transfer methods or non-viral methods, such as DNA-based transposons, CRISPR/ Cas9 technology or direct transfer of in vitro transcribed-mRNA by electroporation.



Significance of Genome Editing:

These techniques affect different areas such as disease management, basic biomedical research, agriculture, and environmental sciences. They could also be used to customise human characteristics for extra-therapeutic enhancement purposes.

Concerns associated with Genome Editing:


■SafetyDue to the possibility of off-target effects (edits in the wrong place) and mosaicism (when some cells carry the edit but others do not), safety is of primary concern. 


■ The International Summit on Human Gene Editing, 
Due to  the possibility of off-target effects (edits in the wrong place) and mosaicism (when some cells carry the edit but others do not), safety is of primar

■ Informed Consent
It is impossible to  obtain informed consent for germline therapy because the patients affected by the edits are the embryo and future generations.

■Many people have   moral   and  religious  objections to the use of human embryos  for  researcher .


■ potential loss to diversity:

 Diversity in all  species of animals is a key to evolution on earth. Genetically engineering  our species will have a detrimental effect on genetic  diversity.



■ No Guarantee of Food Security:


In India, there is a moratorium on Bt brinjal because there is no scientific consensus on its safety and efficacy. 

THREE PARENT BABY

Techniques to create ‘three-parent babies’ seek to offer mothers a way to have a child without passing on metabolic diseases caused by faulty mitochondria.

 



 Researchers do this by exchanging the diseased mitochondria of a prospective mother with those of a healthy, unrelated donor: the ’third parent.’ 

■In addition to DNA in the nucleus, some DNA is also present in the mitochondria.

 ■This technology uses technique of Pronuclear Transfer. 


■In pronuclear transfer, a zygote is created by first fertilising the mother’s egg with the father’s sperm.


 ■The donor egg is then fertilised and has had its own nucleus removed before the pronuclei of the egg and sperm are removed from the zygote and put into the donor egg (a pronucleus is the nucleus of the egg or sperm at the stage of fertilisation prior to nucleus fusion). 


■The donor egg’s zygote is subsequently inserted into the mother’s uterus. 


■During fertilisation the nuclear DNA is formed with 46 chromosomes (i.e., 23 from mother & 23 chromosomes from the father).


 ■The Mitochondrial DNA has only one chromosome and its codes for only specific proteins responsible for metabolism.



 ■Mitochondrial DNA is inherited only from the mother & thus it is more effective to trace human ancestry.


SOMATIC CELL NUCLEAR TRANSFER 


■ Somatic Cell Nuclear Transfer (SCNT), technique in which the nucleus of a somatic (body) cell is transferred to the cytoplasm of an enucleated egg (an egg that has had its own nucleus removed). Once inside the egg, the somatic nucleus is reprogrammed by egg cytoplasmic factors to become a zygote (fertilised egg) nucleus. 

■The egg is allowed to develop to the blastocyst stage, at which point a culture of embryonic stem cells (ESCs) can be created from the inner cell mass of the blastocyst.

FOR EXAMPLE, Cloning of Dolly sheep
 

■Dolly was cloned from a cell taken from the mammary gland of a six-year-old Finn Dorset sheep and an egg cell taken from a Scottish Blackface sheep.

 ■She was born to her Scottish Blackface surrogate mother on 5th July 1996.

■ Dolly’s white face was one of the first signs that she was a clone because if she was genetically related  to her surrogate mother, she would have had a black face.


 Because Dolly’s DNA came from a mammary gland cell, she was named after the country singer Dolly Parton.


























































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