Cells, the Future Therapy
With progress at
different levels, stem cells are showing potential for commercial
success and significant business opportunities.
Advances in biological sciences and the development of human stem cells
are today bringing new hope for the treatment of many diseases such as
Parkinson’s, diabetes, heart diseases and cancer, as well as
injuries for which there has previously been no effective treatment.
Stem cell research and the accompanying enabling technologies have
virtually exploded since embryonic stem cells were first isolated in
1998. Many of the enabling and complementary technologies impacting
stem cells are also catching up.
Induced pluripotent stem cells or iPS cells have been a big
breakthrough in the stem cell research arena. Dr Thomson and his team
of researchers successfully reprogrammed the human adult skin cells to
act like human embryonic stem cells. The breakthrough it is said is
likely to change the course of action making research on embryonic stem
cells redundant, given that iPS cells are remarkably similar to human
embryonic stem cells. Besides researchers can skirt all the ethical
issues related to human embryonic stem cells (hES) and can make as many
iPS cells they need for research.
Progress in stem cell research is now astounding and over 2,000
research papers on embryonic and adult stem cells are being published
in reputable scientific journals every year. While embryonic stem cell
research has yet to yield any clinical trial result, adult stem cells
are already being used in treatments for several conditions including
leukemia, Hunter’s syndrome and heart disease.
In the early 1900s European researchers realized that the various type
of blood cells e.g., white blood cells, red blood cells and platelets
all came from a particular “stem cell”. However, it
was not until 1963 that the first quantitative descriptions of the
self-renewing activities of transplanted mouse bone marrow cells were
documented by Canadian researchers Ernest A McCulloch and James E Till.
Research into adult stem cells in animals and in humans has been
ongoing since this time, and bone marrow transplants--actually a
transplant of adult stem cells--have in fact been used in patients
receiving radiation and chemotherapy since the 1950s.
Developments in biotechnology in the 1980s and 1990s saw the
introduction of techniques for targeting and altering genetic material
and methods for growing human cells in the laboratory. These advances
really opened the doors for human stem cell research.
Then in 1998 James Thomson, a scientist at the University of Wisconsin
in Madison, successfully removed cells from spare embryos at fertility
clinics and grew them in the laboratory. He launched stem cell research
into the limelight, establishing the world’s first human
embryonic stem cell line which still exists today.
Since this discovery, a plethora of evidence has emerged to suggest
that these embryonic stem cells are capable of becoming almost any of
the specialized cells in the body and therefore have the potential to
generate replacement cells for a broad array of tissues and organs such
as the heart, liver, pancreas and nervous system.
The possibilities for stem research are truly endless, and yet
unpredictable. In this nascent, but rapidly growing field of stem cell
therapies, products are taking time to reach the commercialization
stage. However, the market potential for stem cell therapies is assumed
to be very huge. And according to a Business Insights report, the
market for stem cell products and services is forecast to grow almost
three-fold from $24.6 billion in 2005 to $68.9 billion in 2010 and
during the last few years over 2,000 US patents claiming stem cell
technologies and applications relevant to health care were published.
It also mentions that the proportion of stem cell patents claiming
applications in hematology decreased after 1999, while the proportion
of patents claiming applications in neurology, type 1 diabetes,
cardiology and drug screening increased dramatically in the last few
years and over 100 companies with proprietary human adult stem cell
technologies and products have been identified.
Stem cell research in India gained attention when the US Department of
Health disclosing its interest in funding stem cell research in two
Indian Centers--the Reliance Life Sciences and the National Center for
Biological Sciences. The National Center for Biological Sciences had
been working on stem cells for quite long and has three documented stem
India has no clear policy regulating stem cell research but the country
has its fair share of research going on--though blazing success stories
from India are yet to come by. Also, the Indian regulations are by far
more relaxed than some other countries in the region. The Indian
regulatory environment is quite supportive of stem cell research.
“However, there is a need for regulation of individual
investigator initiated cell based therapies, as
these tend to be conducted in variance with international standards of
clinical trials and cell processing and the imponderables on safety and
efficacy are not scientifically addressed,” said KV
Subramaniam, president and CEO, Reliance Life Sciences.
In India several scientific departments and institutions of the
government, such as Department of Biotechnology, Department of Science
and Technology, Indian Council of Medical Research and Council for
Scientific and Industrial Research are promoting stem cell research.
The priority areas of research have been identified through discussions
at various forums on basic and applied sciences.
Among the various programs being supported in embryonic and adult stem
cells research in India are: establishment of hESC lines, use of limbal
stem cells for repair of ocular surface disorders, isolation;
purification and characterization of hematopoietic, mesenchymal cells
Reliance Life Sciences is developing a wide range of novel
research-led, autologous and allogenic cell therapies and
tissue-engineered products to get into regenerative medicines business.
Under the “regenerative medicine initiative”, the
company has several groups who work in areas such as embryonic stem
cells, ocular stem cells, haematopoietic stem cells and skin and tissue
One of the newest companies in stem cell research in India is
Stempeutics Research Private Ltd, a Bangalore-based company focused on
research, therapeutics and therapy in the field of regenerative
medicine. Dr BN Manohar, president, Stempeutics confirms that the
company has developed cell characterization for purity and identity by
flow cytometry, functional assay for multipotency, process validation
for manufacturing, large scale cGMP complaint up-scaling of mesochymal
stem cells and quality control testing and quality assurance.
Stempeutics has also established cell and tissue manipulation
facilities at Bangalore, Manipal and Kuala Lumpur in Malaysia.
“India has massive potential for stem cell research as there
is a very good environment and we have things going for us,”
Another major institute involved in stem cell research in India is the
Stem Cell Biology Department at NIRRH, Mumbai headed by Dr Deepa
Bhartiya. The LV Prasad Eye Institute, based at Hyderabad caught the
headlines recently when its doctors succeeded in transplanting a stem
cell derived cornea to a patient who had lost his cornea - a treatment
option available only in the US at the time. The Maulana Azad Medical
College, Delhi is yet another major institution involved in stem cell
The future of stem cells
Experts predict a rapid progress in adult stem cells and slower but
intense work with embryonic stem cells. It is hoped that, by that, by
2020, researchers will be able to produce a wide range of tissues using
adult stem cells, with spectacular progress in tissue building and
repair. In some cases, these stem cells will be actually incorporated
into the new repairs as differentiated cells.
The future may also see some exciting new pharmaceutical products in
the pipeline. These drugs may, for example, activate bone marrow cells
and encourage them to migrate to parts of the body where repairs are
And experts predict that along the way there will be a number of new
biotech companies folding, as a result of good investment into adult
stem cell technology. The emergence of cord blood banking itself has
created more than a dozen companies globally in a span of 2-3 years.
Cord-blood cell transplants are becoming common as a therapy for
diseases of the blood as scientists are finding that stem cells from
umbilical cord blood may be able to grow into other kinds of cells as
well. Such advances are casting cord blood, previously regarded as
medical waste left after childbirth, in a new light. Today doctors use
cord blood cells to treat about 70 diseases, mostly anemias or cancers
of the blood, such as leukemias and lymphomas.
A yet another area of future research concerns the delivery of stem
cells to the tissues in which they are needed. Current practice
involves either the injection of stem cells directly into the targeted
tissue, or injection of the stem cells into the bloodstream without any
guarantee that they will actually find their way to the appropriate
tissues. Targeted delivery would ensure that the therapeutic stem cells
are introduced to the organs and tissues that need them, where they
Engineering Using Stem Cells, a Panacea for Infertility
—Dr. Chander P
Puri, CEO, Yashraj Biotechnology Limited
Over the last few decades, we have witnessed exemplary advances in
science especially in the arena of biotechnology, an umbrella term
covering a wide range of scientific applications for the benefit of
mankind. Till very recently, biotechnology-based endeavors had been
aimed to discover new methods to produce biomolecules in vivo or in
vitro with the intent of using them for detection or treatment of
various pathologies afflicting humans or animals.
Now biologists are facing another challenge, a very threat to the
perpetuation of human life i.e. infertility. Although at this juncture,
infertility statistics worldwide are not alarming, these incidences are
steadily intensifying. This has compelled biologists to take the onus
for devising innovative ways to preserve fertility or treat
infertility. And in this pursuit, they have been immensely benefited by
the legacy of almost 30 years of in vitro fertilization techniques
leading to a groundbreaking discovery of embryo or adult cell derived
Embryo derived primitive cells or embryonic stem (ES) cells
are endowed with a potential to give rise to every tissue type in the
body, hence it was envisaged that two indispensable progenitors of a
new life i.e. eggs and sperm could also be generated from
these cells outside the human body. This hypothesis so far has proven
well-grounded and efforts in this direction have not been futile.
Researchers at the University of Pennsylvania, US, have been able to
develop mouse eggs in vitro from few ES cells grown separately. Male
germ cells have also been derived from mouse ES cells and these cells
have resulted in live births.
It has been demonstrated that premeiotic and haploid germ cells derived
in vitro can successfully fertilize oocytes, produce embryos and live
pups. However, the animals born of the fusion of the in vitro developed
male germ cell and the normal oocyte were found to be infertile,
abnormally large and had stunted growth, probably due to genetic
defects arising during the creation of the sperm. While further
research is needed to obviate the possibility of genetic or epigenetic
errors accruing during the ex vivo creation of male and female gametes,
these success stories in mouse, have enthused researchers to generate
human gametes in vitro. Studies indicating the expression of egg and
sperm specific markers in spontaneously differentiating human ES cells
in vitro have strengthened the belief that the derivation of gametes is
feasible from human ES cells.
Studies are also being undertaken to develop germ cells or gametes
without using embryonic stem cells. Porcine fetal
skin–derived stem cells have been induced to differentiate
into oocyte-like cells within follicle structures. The potential of
bone marrow stem cells has also been explored in treating male
infertility in mouse models. Researchers at the Harbor-UCLA Medical
Center observed the characteristics of germ cells in the bone marrow
stem cells which were injected into the testes of infertile mice.
Although these germ cells did not differentiate fully into sperm, these
studies highlighted the relevance of other factors or cellular signals
required for complete differentiation of sperm.
The recent finding that some human embryonic stem cell (hESC)
lines display greater propensities to differentiate along certain
lineages than others suggests that some ESC lines could produce gametes
more efficiently that others. Establishing the right micro-environment
where germ cells can thrive naturally among other fetal gonadal cells
will be the key. Indeed, the factors that support germ cell development
have been found to be useful in enhancing the derivation rates of germ
cells from ES cells. Considering the limitations of adult cell derived
stem cells and the ethical issues associated with ES cells, attempts
have been made to develop stem cells from adult differentiated cells.
Researchers have identified several genes that can dedifferentiate
adult cells into stem cells. These dedifferentiated cells, called iPS
cells can be reprogrammed into the cells that eventually become eggs
and sperm and this may open up new vista for the treatment of
infertility using patient-specific cells. However the major challenge
in translation of these research observations for human use is how to
generate high quality germ cells in the lab. Germ cell derivation
remains very inefficient process with less than one of one million
starting cells becoming a germ cell. The poor efficiency of this
process has been attributed to the failure of meiosis and/or the
simultaneous activation of both male and female germ cell programs in
ESC-derived gametes resulting in meiotic catastrophe. There
are many uncertainties and dangers associated with the use of iPS also.
As the process of reprogramming involves viruses for gene delivery, it
potentially increases the likelihood of genetic abnormalities and
cancers. Research endeavors are in full swing to surmount the obstacles
currently being encountered in generation of immature and mature
It is hoped that with the ex vivo generation of human sperm and egg,
infertility will soon become ‘a thing of the past’.
The eggs and sperms created in vitro may help people who lose such
cells because of age or certain pathologies such as cancer or ovarian
disorders. These techniques will also have appealing spin-offs such as
reproductive cloning of farm animals.