VELAMMAL VIDHYASHRAM

MAMBAKKAM

ALL INDIA SENIOR SCHOOL

CERTIFICATE EXAMINATION

BIOLOGY
INVESTIGATORY PROJECT REPORT
2021 – 2022
LIVER CIRRHOSIS AND STEM CELL THERAPY

NAME – RAKSHANA.R

ROLL NO. -

GRADE - XII

SECTION- C

GROUP – BIO-MATHs
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 BONAFIde CERTIFICATE
This is to certify that this BIOLOGY Investigatory Project on the
topic LIVER CIRRHOSIS AND STEM CELL THERAPY has been
successfully completed by RAKSHANA.R of class XII(BIOLOGY),
Roll.no…………………. at Velammal Vidhyashram, Mambakkam for
the partial fulfilment of this project as a part of All India Senior
School Certificate Examination-CBSE, New Delhi for the
academic Year 2021– 2022.

Date: …………………….

Signature of Principal Signature of the Guide

Name:Mr.R.ARULKUMAR Name: Mrs.MATHURA

Submitted for AISSCE 2021-2022, BIOLOGY Practical

examination on ………………….

Signature of the Signature of the

Internal Examiner External Examiner

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 ACKNOWLEDGEMENT

The success of any project depends largely on people

associated with it. I would like to take this opportunity to
acknowledge the enthusiasm of all these personalities.

I hereby express my heartfelt thanks to our Senior

Principal Mr.R.ARULKUMAR for having given this
opportunity to do the project in the chemistry laboratory
and for his constant encouragement.

I extend my sincere gratitude to acknowledge my

sense of gratitude to my Biology teacher Mrs. MATHURA
for the valuable guidance offered to me. Her whole-
hearted encouragement and constant stimulant
inspiration and advice enabled me to complete the project
successfully.

I am also thankful to all our teachers and Non-

Teachers for their help during my course of study.

I take this opportunity to express my sincere thanks

to my parents for their encouragement and support.
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 INDEX

S.No Contents Page

1 Bonafide certificate 2
2 Acknowledgement 3
3 Introduction 5-7
4 Liver Transplantation 8-10
5 Stem Cells Therapy 10-14
6 Liver Regeneration 15-21
7 Comparison of Liver Transplantation and stem 22
cell Therapy
8 Summary and Conclusion 22-23
9 Bibliography 24

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INTRODUCTION :
What is Liver Cirrhosis?
Cirrhosis is a condition in which the liver slowly deteriorates and
malfunctions due to chronic injury. Scar tissue replaces healthy
liver tissue, partially blocking the flow of blood through the liver.

How does it affect the individual

Cirrhosis affect's the liver's ability to:
 control infections.
 remove bacteria and toxins from the blood.
 process nutrients, hormones, and drugs.
 make proteins that regulate blood clotting.
 produce bile to help absorb fats—including cholesterol—
and fat –soluble vitamins.
 Also Increases the pressure in portal venous system.

Causes of liver cirrhosis

 Hepatitis C Virus.
 Long term Alcohol abuse.
 Auto immune inflammation of liver.
 Hepatitis B Virus.
 Metabolic Diseases of - Copper -Wilson's Disease .
 Iron-Hemochromatosis.
 Nonalcoholic fatty liver disease(NAFLD).
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  Nonalcoholic Steatohepatitis(NASH).
 Reaction to certain Medicines.

Symptoms
Symptoms may develop gradually, or there may be no symptoms.
When symptoms do occur, they can include:
 Abdominal indigestion or pain.
 Confusion or problems thinking.
 Impotence, loss of interest in sex, and breast development
(gynecomastia) in men.
 Nausea and vomiting.
 Ascites (Ascites is excess fluid in the space between the
tissues lining the abdomen and abdominal organs (the
peritoneal cavity).
 Nosebleeds or bleeding gums.
 Pale or clay-colored stools.
 Small, red spider-like blood vessels on the skin.
 Vomiting blood or blood in stools.

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Is liver transplant the only option?

In early stages, the answer is no.

✓ Following changes in life style may slow down the
progression of the disease.
✓ Stop drinking alcohol.
✓ Get vaccinated for hepatitis A and hepatitis B, and
pneumococcal pneumonia.
✓ Tell your doctor about all prescription and nonprescription
medications, and any herbs and supplements you take now
or are thinking of taking.
Other treatment options are available for the complications
of cirrhosis:
➢ Bleeding varices -- upper endoscopy with banding and
➢ Sclerosis.
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 ➢ Excess abdominal fluid (ascites) -- take diuretics, restrict
fluid and salt, and remove fluid (paracentesis).
➢ Confusion or encephalopathy -- lactulose medication and
antibiotics.

But in end stages, yes, Liver transplant is the only viable

option.

Basic mechanism of liver transplantation :

• Virtually all liver transplants are done in an orthotopic fashion,

that is, the native liver is removed and the new liver is placed in
the same anatomic location.

• The transplant operation can be conceptualized as consisting of

the hepatectomy (liver removal) phase, the anhepatic (no liver)
phase, and the post implantation phase.

• The operation is done through a large incision in the upper

abdomen. The hepatectomy involves division of all ligamentous
attachments to the liver, as well as the common bile duct, hepatic
artery, hepatic vein and portal vein.

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• The donor's blood in the liver will be replaced by an ice-cold
organ storage solution, such as UW (Viaspan) or HTK until the
allograft liver is implanted. Implantation involves anastomoses (
connections ) of the inferior vena cava, portal vein, and hepatic
artery.

• After blood flow is restored to the new liver, the biliary (bile
duct) anastomosis (link) is constructed, either to the recipient's
own bile duct or to the small intestine.

Limitations of Liver transplantations :

✓ Life long immuno suppression.

✓ Cost .
✓ Availability.
✓ Shortage of donors.
✓ High mortality during waiting period.

Stem cells – Details and Therapy :

Definition:
Stem cells are biological cell found in all multi-cellular organisms,
that can divide (through mitosis) differentiate into diverse
specialized cell types and can self-renew to produce more stem
cells.

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  Stem cells are those cells that have the capability of self-
renewal and differentiation.
 Self-renewal is the ability of cells to proliferate without the
loss of differentiation potential and without undergoing
senescence (biologic aging).
 A stem cell is a blank cell/ precursor cell that can give rise to
multiple tissue types such as a skin, muscle, or nerve cell.
 A stem cell is essentially the building block of the human
body.

Features of Stem Cells :

1. Stem Cells are very unique cells.
2. Stem Cells have the amazing ability to develop into
several distinct cell types in the body.
3. Stem Cells can be used as a repair system for the body.
4. Stem Cells can theoretically divide without limit in a living
organism in order to replenish various types of cells.
5. When a stem cell divides, each new cell has the potential
to either remain a stem cell or become another type of cell
with a more specialized function (i.e. a muscle cell, a red
blood cell, a brain cell, etc.).

Three unique properties of stem cells :

1. Stem cells are capable of dividing and renewing
themselves for long periods;
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 2. They are “unspecialized” and they can give rise to
specialized cell types.
3. A stem cell is "uncommitted," until it receives a signal to
develop into a specialized cell.
Importance :
They are capable of forming most of the cells in our body and thus
can be used in replacement of dead/ nonfunctional cells and can
save miraculously save individuals who might me paralysed for
life.
1. Source of Stem cells :
❖ Stem cells may be derived from autologous, allogeneic
or xenogenic sources.
❖ Histocompatability is prerequisite for transplantation
of allogeneic stem cells.
❖ Fatal tissue is the best current tissue source for human
neural stem cells, however ethical issues are a major
concern.
2. Potential sources of stem cells are:
Fetal tissue that becomes available after an abortion excess
embryos from assisted reproductive technologies such as
commonly used in fertility clinics embryos created through
in vitro fertilization specifically for research purpose, and
embryos created asexually as a result of the transfer of a
human somatic cell nucleus to an egg with its own nucleus
removed.
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Other sources of stem cells are those from umbilical cord
blood, and bone marrow. In addition, neural stem cells,
haematopoetic stem cells and mesenchymal stem cells can
be harvested from fetal blood and fetal tissue.

3. Placenta a Source of Stem Cells Placental stem cells, like

umbilical cord blood and bone marrow stem cells, can be
used to cure chronic blood-related disorders such as sickle
cell disease, Thalasemia, and leukaemia.

4. Umbilical Cord Blood Stem Cell Transplant Umbilical cord

blood stem cell transplants are less prone to rejection than
either bone marrow or peripheral blood stem cells. This is
probably because the cells have not yet developed the
features that can be recognized and attacked by the
recipient's immune system.

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LIVER REGENERATION :

One of the defining characteristics of liver is its capacity to

maintain a constant size despite injury. Although the precise
molecular signals involved in the maintenance of liver size are not
completely known, it is clear that the liver delicately balances
regeneration with overgrowth.

Mammals, for example, can survive surgical removal of up to 75%

of the total liver mass. Within 1 week after liver resection, the
total number of liver cells is restored. Moreover, liver overgrowth
can be induced by a variety of signals, including hepatocyte
growth factor or peroxisome proliferators; the liver quickly
returns to its normal size when the proliferative signal is
removed.

One of the primary reasons for this controversy is the use of

multiple definitions for the hepatic stem cell. Definitions for the
liver stem cell include the following:
1) Cells responsible for normal tissue turnover.
2) Ccells that give rise to regeneration after partial
hepatectomy,
3) Cells responsible for progenitor dependent regeneration,
4) Cells that produce hepatocyte and bile duct epithelial
phenotypes in vitro.
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 5) Transplantable liver-repopulating cells.

Cell based strategies are of two types :

1. Direct infusion of adult /fetal hepatocytes.

2. Infusion of stem cells.

1. Hepatocyte transplant as an alternative :

It has been in use for more than 30 years. However the

problem with hepatocyte transplantation is that of availability of
adult/fetal human hepatocytes in adequate numbers. The other
problem is that they still require immunesuppression.).Xenogenic
hepatocyte transplantation has also been tried however it has
got lurking fear of retroviral transmission and tumor genesis.

2. Stem cell therapy as an alternative of liver transplantation :

Cellular based therapies promise a great future for a variety of

diseases involving various organs. It has been used in conditions
as diverse as degenerative disorders of musculoskeletal system
and CNS, cardiomyopathy and trauma. In liver diseases the stem
cells have been utilized in various metabolic genetic diseases with
presentation of proof of principle.

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Cells That Give Rise to Regeneration After Partial
Hepatectomy :

Partial hepatectomy is a surgical procedure in which specific liver

lobes are removed intact without damage to the lobes left behind.
The process has been extensively studied and is the subject of
several excellent reviews. The excised liver lobes never grow
back, but the remaining lobes grow to compensate for the mass of
the resected tissue. Reconstitution of the entire liver mass, which
is complete within 5–7 days in rodents, is mediated by mature cell
types (ie, without stem cells).

Multipotent adult progenitor cells as hepatocyte progenitors:

Multipotent adult progenitor cells are a unique population of

progenitors from multiple mammalian species that are generated
in longterm culture by plating nonhematopoietic adherent cells
from the bone marrow.These cells have been reported to have
properties similar to embryonic stem cells in that they can be
differentiated toward multiple lineages in vitro under the
appropriate conditions.

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When grown on Matrigel with fibroblast growth factor 4 and
hepatocyte growth factor, multipotent adult progenitor cells
generate hepatocyte-like cells that synthesize urea, secrete
albumin, and induce cytochrome p450 in response to
phenobarbital.

Hepatocytes as Liver- Repopulating Cells :

Liver repopulation is unique among organ systems. In contrast to

the hematopoietic system, where mature adult blood cells have
minimal proliferative capacity,Differentiative hepatocytes
themselves have high capacity for liver repopulation. First,
mature hepatocytes (identified by size fractionation, retroviral
marking,or serial transplantation) were transplanted into livers
of Fah knockout mice. Large binucleated hepatocytes that
represented 70% of the hepatocyte population were found to
mediate most of the liver repopulation.

Types Of Stem Cells employed in Liver transplantation :

Basically three types :

• Embryonic
• Fetal
• Adult

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Embryonic:
❖ Omnipotent.
❖ Can differentiate into any cell type.
❖ Limitations of availability, ethical issues.

Fetal:
❖ Totipotent.
❖ Source is 20-24 week fetus.
❖ Limited supply.

Adult:
❖ Maintaining the stability of metabolic function.
❖ Difficulties in cryopreservation.
❖ Immunogenicity.
❖ Cannot proliferate in vitro Stem Cell therapy.

Transplantable Liver :

Repopulating Cells :

One of the hallmarks of tissue-specific stem cells is their capacity

to repopulate a specific organ and restore its function.

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➢ HSCs, for example, were identified based on their ability to
reconstitute blood lineages in lethally irradiated hosts.

➢ Over the past 2 decades, similar assays were developed to

identify liver stem cells; a small number of transplanted
donor cells were found to engraft in the liver and expand to
replace 50% of the liver mass.

➢ Such models allow for the replacement of only hepatocytes

by transplanted cells. Efficient repopulation of the blilary
system has not been reported, but it is possible to
functionally evaluate hepatic stem cell populations based on
their capacity for liver repopulation.

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 Comparison of Liver transplantation and stem
cell therapy

Summary & Conclusion:

The ability of stem cells to form new hepatocytes has proved to be

a boon for patients all over the world suffering from a number of
liver related diseases such as Liver Cirrhosis.In the past, liver
transplantation was the only option, but with the help of latest
technology and our knowledge of stem cells, we can now use Stem
Cell Therapy as a new methodology of curing liver diseases.

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Thus,we can conclude that stem cells have a bright future not just
in hepatology but in a wide variety of fields.

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 BIBLIOGRAPHY

 Stem cells and Liver generation – Andrew W.Duncun,Craig

Dorren and Markus GPompe
http://www.gastrojournal.org/article/S0016-
5085%2809%2900818-X/abstract.
 Liver Cirrhosis by John Susan.
 A Proposed Novel Stem Cell Therapy Protocol for Liver
Cirrhosis by po cheng Lin and Tzyy-Wen Chiou.


Could Stem Cell Therapy be the Cure in Liver Cirrhosis?
Article by Ahmer Irfan and Irfan Ahmed

 Regenerative Medicine and Cell Therapy by Hossein

Baharvand and Nasser Aghdami

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