Stem stem cell transplant and donation can

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cell transplantation is a procedure where patient is a recipient of healthy
blood-forming stem cells in replacement of their stem cells that may have been
destroyed by disease or radiation or high doses of anticancer drugs that are administered
as part of the treatment. The stem cells could be obtained from peripheral blood
or bone marrow of the patient, from a donor, or from the umbilical cord blood
of a new-borns. Stem cell are primary precursor cells of many linage that matures
into a functional cell through a series of cell divisions, maturations and
specialization. They are involved in repairing cellular system as they are
unlimitedly produced in an individual as the stem cells divides with potential
to remain as stem cells or may be induced to become other cell types that may
be tissue or organ specific and they are equipped with specialised functions
such as muscle cells, brain cells and red blood cells. A stem cell transplant
and donation can be done by autologous, allogeneic or syngeneic stem cells
where haematopoietic stem cell transplants serves as a routinely implemented
treatments used to treat cancer, blood disorders and immune system disorders. For
example, the hematopoietic stem cells in the bone marrow can give rise to red
blood cells, white blood cells and platelets. There are mainly four different
types of stem cells, in which are embryonic stem cells, tissue-specific stem
cells, mesenchymal stem cells and induced pluripotent stem cells.

history of stem cell transplantation begins in 1939 where the first attempt of human
bone marrow transfusion occurred as stem cells transfusion was given to a patient
with aplastic anaemia as treatment along with daily transfusion of blood and
intravenous injection of bone marrow in attempt to raise the leukocyte and
platelet count of the patient, regardless the treatment was unsuccessful.
However, the bone marrow transfusion has been accepted as a treatment ever
since regardless of the unstable progress and problems encountered such as
graft-versus-host disease (GVHD). Shortly after the usage of atomic bomb in
World War II, researchers begun to find methods in restoring bone marrow
function in aplasia due to radiation exposure and was later proven in the 1950s
in a mouse model that bone marrow aplasia secondary to radiation exposure can
be treated by syngeneic bone marrow graft. Whereas in 1956, researcher Barnes
and colleagues have published their experiment done on two groups of mice both
with acute leukaemia where both groups are treated as anti-leukemic therapy and
that both groups recovered from bone marrow aplasia by bone marrow
transplantation. However, group one was treated with syngeneic marrow(same strain)where most of
the mice died in result of leukaemia relapse and group two was treated with allogenic marrow(diff strain) where
none of the mice showed leukaemia relapse but all died due to wasting syndrome.
As a result of the experiment, three major principles of haematopoietic stem
cell transplantation (HSCT) demonstrated are the role of the preparative anti-leukemic
regimen in HSCT, the ability of the new engrafted immune system to prevent
leukaemia relapse and the activity of the engrafted immune system against the
recipient. The first allogeneic HSCT that has led to its current status was instigated
by E. Donnall Thomas and reported in the New England Journal of Medicine on
September 12, 1957 (Thomas et al., 1957).

Stem cells transplants are needed to re-establish
hematopoietic function in patients whose bone marrow or immune system is
defected or damaged by either autologous or allogeneic stem cells transplantation.
Haematopoietic stem cell transplantation HSCT is needed as one of the routine
treatment for multiple myeloma, Hodgkin disease, germ cell tumours, amyloidosis
and autoimmune disorders such as systemic lupus erythematous (SLE) and systemic
sclerosis that are to be treated by infusion of autologous stem cells
transplantation. Where acute myeloid and lymphoblastic leukaemia (AML, ALL),
chronic myeloid and lymphoblastic leukaemia (CML, CLL), aplastic anaemia,
Fanconi anaemia, thalassemia major, sickle cell anaemia, severe combined
immunodeficiency (SCID) are treated with allogenic stem cells transplantation.

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Stem cells sources could be obtained and found at
human umbilical cord tissue where it has abundant amount of mesenchymal stem
cells, plus it is most suitable for tissue regeneration due its tissue
repairing function, immune system modulation and reducing inflammation. Stem
cells can also be obtained from bone marrow, cord blood and adipose tissue
being the source of CD34+ stem cells that aids in tissue regeneration via
revascularization and support provided to mesenchymal cells, and majority of
protocol uses cord blood for Human Leukocyte Typing (HLA) to for compatibility
testing. Stem cells from adipose tissue is contains T-regulatory cells which
modulate the immune system and it is also used to treat systemic autoimmune and
inflammatory conditions.

The different types of transplants varies upon the
collection of the stem cells where there are autologous, allogenic, haploidentical,
syngeneic, peripheral and cord blood stem cell transplantation. Autologous stem
cell transplant are healthy and normal stem cells collected from patient’s own
blood or marrow where the healthy stem cells will find its way to the bone
marrow and begin to produce new healthy cells after the treatment. Allogeneic
stem cell transplant are stem cells are collected from a related or unrelated
donor where it aids in restoring the haematopoietic cells of the bone marrow in
patient. An allogeneic related donor’s stem cells genetically matched to the
highest proximity where the donor could be sibling or parent. The degree compatibility
is tested by HLA typing. An allogeneic unrelated donor (URD) has similar
genetic typing to patient but is not related. Where the possibility to find
similar matches for patients that do not have a related donor is made possible
by The National Marrow Donor Program (NMDP) where the registry is comprised of
volunteer donors and new donors are updated to the list daily. Haploidentical
stem cell transplant are stem cells are obtained from a parent or a related or
unrelated donor where the genetic match is at least half identical to the
recipient. Syngeneic stem cell transplant occurs where stem cells are donated
by an identical twin as they have the same genetic types and are often
considered as a perfect match. Peripheral stem cell transplant are obtained
from the peripheral blood by apheresis as the stem cells are selected out by
the apheresis instrument, and the remainder of the blood is returned to the
patient, the process takes about 3 to 4 hours per day. This type of stem cells
are used often in the autologous setting. Cord blood stem cell transplant are
collected from the umbilical cord or the placenta immediately after birth then cells
are frozenly stored for future use where the donor can be a sibling or unrelated

Haematopoietic stem cell collected from peripheral
blood after a 5day course of granulocyte colony stimulating factor
administration on 1-2days via 4-5 hours of apheresis through peripheral blood
donation. This collection method is relatively an easier, effective and safer
method. Umbilical cord blood are collected by double clamping and transects the
cord within 30seconds upon the delivery of new-born where the free end of the
cord is sterilised with betadine prior collection, also the umbilical vein is punctured
and the cord blood will be collected by gravity in the collection bag if the
placenta was still in uterus. The collection bag used are triple bag with 450ml
bag each contains citrate-phosphate-dextrose-adenine (CPD-A) anticoagulant.
After collection the units are stored at 4°C, transported to the bank with the
corresponding paperwork and is processed within 24hours, in which 3 ml of
samples per unit are later taken for HLA typing, a nucleated cell (NC) count,
CD34+ cell count and progenitor cell assays. Before the processing begins,
volume reduction is carried out in prior and fungal, aerobic and anaerobic
bacteriology cultures were performed on all donations. Cryopreservation of cord
blood protocol was done by 1°C/min cooling down to ?60°C, followed by a drop to
?120°C, 5°C/min which the cells were stored in the liquid phase of a liquid
nitrogen freezer at the end of the freezing procedure. PBSC is usually stored
for a up to 33 days whereas bone marrow HSC stored for more than 10 years yet
there is no loss of CFU and CD34– cells.29 When cord bloods were
cryopreserved for either 2-8 weeks or for 15 years, the MNC recovery,
clonogenic potential and proliferative and cytotoxic responses against HLA
antigens were maintained.10

However, there is also presence of risks of
transplantation that includes graft-versus-host disease (GVHD), graft failure,
organ damage, infections, cataracts, infertility new cancers, death. Problems
to overcome/issues faced in all types of transplants are the myeloablative
regimens that are highly toxic, high peri-transplant morbidity and mortality
rate, complications with infections, bleeding tendencies, and the stem cells
are required to be infused immediately. Where as in case of allogenic transplants
high count of contaminating red cells that might lead to ABO or Rhesus (Rh)
incompatibility hence infusion of incompatible RBC with donor bone marrow,
triggering haemolytic transfusion reaction. Besides, histocompatibility is also
a main concern as there is a high risk of graft versus host disease upon any
mismatch to the patient. Supportive care is very essential post transplantation
to manage any possible adverse reaction and to ensure the successful
transplantation without any GVHD that may lead to death of patient post
transplantation. Besides, cautiously monitoring the immunosuppressant drug
intake is also very essential as that may lead to side effects such as bleeding
tendency, disseminated intravascular coagulation and high tendency to diseases
upon exposure to infectious agent.

In my opinion, stem cells transplantations are
generally an advanced technique that has been developed in aid to treat
multiple myeloma, different types of leukaemia and other cancer cases as well
as inborn-error such as sickle cell anaemia, SLE, thalassemia major, aplastic
anaemia and severe combined immunodeficiency (SCID). However, there also
disadvantages that complies upon treatment in which are the treatment are
relatively expensive hence it is not accessible to the public, as well as the
rare cases of patients with rare HLA typing that adds to the level of
difficulty into getting a match. Plus, certain groups are opposing the
treatment proclaiming that it is a form of manipulating or interrupting the
perfect divine creation of God is morally wrong by interfering genomes, however
I believe we have the authority to intervene, in purpose of to heal and
restore, but not to manipulate and destroy.

Regardless on the arguments on ethical issues in
stem cell transplantations, recent researches are now focusing on strategies to
decrease the relapse rate of the disease where methods are developed to
manipulate the graft immune system activity towards graft-versus-leukaemia
(GVL) while minimizing the graft-versus-host disease (GVHD). This represents a
totally new and exciting direction in stem cell transplantation in which it
could possibly promote another breakthrough in allogeneic HSCT. Immune response
of donor T lymphocyte against the relapsing leukemic cells are predominantly
due to graft-versus-leukemia, where it also contributes to the immune response
of B lymphocytes and NK cells. There are 49 leading strategies are currently in
the clinical phase of investigation upon graft manipulations in haploidentical
HSCT and vaccinations.

In conclusion, scientists have figured out more
details regarding HSCT throughout the years of advancement and development of
stem cell transplantations where by it has now been routinized and widely
implemented in which benefiting in rapid treatment through infusion as well as
preventing death of patients that are suffering blood metabolism disorders.
Example, the case fatality rate of aplasia anaemia and multiple myeloma are
significantly reduced as patient undergo treatment upon haematopoietic stem
cell transplantation. Despite arguments on ethical conduct issues revolving
around stem cell transplantation, the beneficial of the technique is seemed to
be excessively outwon the arguments on ethical issues as this technique has
saved millions of lives where the treatment is not as invasive as other
available options. Plus, the stem cells transplantation technique and treatment
will be more mature and gets even better with lesser adverse reaction as well
as it may be expanded to ne used as treatment to other diseases with the
emergence of more and more uprising intervention methods and researches.

Categories: Development


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