EXTENDED ABSTRACT
Stem Cell Therapy in
Hematologic Malignancies
A. Harryanto Reksodiputro
Hematologic-Medical Oncology Division, Dept. of Internal Medicine
Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
In recent years stem cells has become the subject of
increasing interest because their utility in numerous
biomedical application. Stem cells are capable of renew in
themselves. They can be continuously cultured in their
undifferentiated state. These undifferentiated cells can be
cultured into more specialized cells such as bone marrow,
heart, liver, pancreatic, blood vessel, and nerve cells. Therefore
they can be utilized in vitro to replace damaged cells and/or to
test drugs or chemicals. The ability to differentiate is the ability
to develop into other cell types. A stem cell can develop into
cells from all three germinal layers.
Tissue engineering is a developing field that combines
biology and engineering in order to create a biological method
which can replace or restore malfunctioning tissues. Cells from
bone marrow or peripheral blood has been cultured in the
laboratory and selected subpopulation of these cells are then
used to treat malfunctioning tissue/organs.
Adult patients suffering from coronary artery and
peripheral vascular diseases continously need small-diameter
vascular graft. In 1986, Science published a report by
Weinberg and Bell who were among the first scientists able to
construct a vessel in the laboratory using collagen and vascular
cells which resembled a normal vessel in structure as well as in
function. In 1999 Niklason demonstrated the feasibility of
creating small arteries in the laboratory that mimics
physiologically pulsatile blood flow and pressure.
Tissue engineering in the cardiovascular system may offer
several advantages over the current treatment. Tissue-
engineered structures contain living cells so that it has the
potential to grow and remodel over the time and might function
for decades or even a lifetime. Since the cells are mostly
derived from the patient who received the implant there should
be no rejection by the immune system; neither thrombus
formation.
Pittengter (1999) published a technique for isolation of
pure mesenchymal stem cells (MSC) which have the potential
to differentiate into fat, bone, cartilage, muscle as well as
cardiac cells. Hoerstrup has described the use of MSC from
bone marrow to create heart valves.
Guleserian et al, reported in 2001 to have been able to
isolate endothelial progenitor cells (EPC) from human
umbilical cord, and demonstrated these cells could grow in
culture in response to vascular endothelial growth factor
(VEGF) and basic fibroblast growth factor (bFGF). In 2002
Hoerstrup reported that EPCs isolated from human umbilical
cord have cellular, extracellular matrix, and biochemical
properties similar to native tissue.
Bone marrow stem cells can become brain cells, liver cells
precursors, heart cells, skeletal as well as smooth muscle.
Harvesting umbilical cord blood poses no risk to mother or
child, whereas a bone marrow donor must undergo anaesthesia
and is exposed to the risk of infection. Because the stem cells
in those in the bone marrow are more primitive from adult
donors, they carry much lower incidence of GVHD.
This makes it possible to perform transplant with less than
perfect matches of type.
Many regenerative therapies are being developed which
use the patient's own stem cell. One of the most common and
promising is the use of stem cell for heart repair ; adult patients
who have banked cord blood would have a ready source of
stem cells regenerative medicine. On the other hand, they also
have a rich source of stem cells in their bone marrow. When
parents bank the cord blood from a new baby, in the near term
they are most likely providing medical insurance fpr the child's
siblings. Only in the long term when the donor grows up will
they have value for self-use.
The diseases in which stem cells has been tried most
widely are bone marrow, heart disease, diabetes, and
Parkinson's disease. Bone marrow stem cells either taken from
the peripheral blood or from the bone marrow have been
widely used and reported.
Only bone marrow transplantations have been performed
in Indonesia in around 1989-1990, one in Yogyakarta, one in
Semarang, one in Bandung and four in Jakarta. Of the four
bone marrow transplantation performed in the Jakarta, one is
done with stem cells that is mobilized from the bone marrow
into the peripheral blood. Financial condition is the main
Cermin Dunia Kedokteran No. 153, 2006
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problem for bone marrow transplantation in Indonesia.
Perhaps the best-known stem cell therapy to date is the
bone marrow transplantation, which is used to treat leukemia
and other types of cancer, as well as various blood disorders.
Leukemia is a cancer of white blood cells, or leukocytes.
Like other blood cells, leukocytes are made in the bone marrow
through a process that begins with multipotent adult stem cells.
Mature leukocytes are released into the bloodstream, where
they work to fight off infections in our bodies.
Leukemia results when leukocytes begin to grow and
function abnormally, becoming cancerous. These abnormal
cells cannot fight off infection, and they interfere with the
functions of other organs.
Successful treatment for leukemia depends on getting rid
of all the abnormal leukocytes in the patient, allowing healthy
ones to grow in their place. One way to do this is through
chemotherapy, which uses potent drugs to target and kill the
abnormal cells. When chemotherapy alone can't eliminate them
all, physicians sometimes turn to bone marrow transplants.
In a bone marrow transplant, the patient's bone marrow
stem cells are replaced with those from a healthy, matching
donor. To do this, all of the patient's existing bone marrow and
abnormal leukocytes are first killed using a combination of
chemotherapy and radiation. Next, a sample of donor bone
marrow containing healthy stem cells is introduced into the
patient's bloodstream.
If the transplant is successful, the stem cells will migrate
into the patient's bone marrow and begin producing new,
healthy leukocytes to replace the abnormal cells.
Bone marrow transplantation (BMT) has been used to treat
lymphoma for over ten years, much of that time on a trial basis
but now much more in the mainstream. Sometimes lymphoma
becomes resistant to treatment with radiation therapy or
chemotherapy. Very high doses of chemotherapy may then be
used to treat the cancer. Because the high doses of
chemotherapy can destroy the patient's bone marrow, marrow
is taken from the bones before treatment. The marrow is then
frozen, and the patient is given high-dose chemotherapy with or
without radiation therapy to treat the cancer. The marrow that
was taken out is then thawed and given back through a needle
in a vein to replace the marrow that was destroyed. This type of
transplant is called an autologous transplant. If the marrow
given is taken from another person, the transplant is called an
allogeneic transplant.
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2005.
Hope is the only good which is common to all men
(Thales)
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