Dr. Himanshu Patel's Blog

Often we encounter one question from the patient and that is how long stem cell will take to respond. We notice most of the time expected answer is sooner or immediate. Unfortunately this is not true for stem cells. And to know that why so one must understand how stem cells works.

Now assume human body as a country and stem cells are new immigrant for this territory. The very first step for new immigrant after entering to the new country is locating the state where they suppose to settle down and then gradually city and street. In terms of stem cell this procedure is called targeting the site where stem cells are targeting the organ and then damage tissue of that organ. Stem cells do this by tracing chemical signaling either release by the damage tissue or brain. The next step for immigrant is get the accommodation at the located site and then start getting acquainted with surrounding culture and life style For stem cells this step is consider as homing, in which stem cells settle at the damage site and get acquainted with surrounding tissue, as at the homing site the tissues are different then the types of stem cells. Being acquainted with surrounding, the immigrant tries to become part of it. In stem cells terminology this is called engrafting, where stem cells convert themselves same as surrounding tissue. Finally the immigrant starts growing and working with community, gathering wealth and settling family. Same way stem cells after engrafting become active and start growing and working to repair the damage tissue. Now looking to these entire procedure one can judge that why sooner or immediate response cannot be possible with stem cell therapy. One has to wait for 1 month to 4months for initiation of any response from stem cell therapy.

The few measures can be taken to make the response faster. One of that is land immigrant at the nearest distance from homing site, likewise inject the stem cells near to the damage organ like heart, spinal cord, liver etc. This can make response faster Instead of IV injection of the stem cells and also can work with less number of cells as this prevent loss of stem cells in circulation. The other measure is \differentiating the stem cells to a lineage near to damage tissue so sooner it can engraft with the surrounding tissue and start working. For example if stem cells are injected to increase vasculogenesis of the tissue than endothelial progenitor cells differentiated from mononuclear cells can induce faster response than mononuclear cells itself not only that even less number of cells gives better response as less amount of cells are lost in engrafting.

News about cricketer Yuvrajsinh’s cancer blew a storm in cricket world. He is suffering from a cancer, which is caused by germ cells. The positive thing in his case is that it is curable. Still the mystery of homing of germ cells in any part of the body other than testis or ovary is not solving 100%.

The germ cells are the cells which further develop in sperm or oocyte, which are some of the most differentiated cells in our bodies, yet they generate all cell types  if body after fertilization. This property, to turn in to any types of the cells is called as totipotency. The zygote and to some extent early blastomeres are totipotent, as they are self-contained entities that can give rise to the whole organism. So other than germ cells early stage embryo is the source of totipotent stem cells for research. The other property of totipotent stem cells is, they can replicate for unlimited number without losing their potency. This could be the one of the reason for developing tumor with totipotent cells. Together with this property and its source the stem cell research with totipotent cells becomes a debated issue.

The germ cell lineage that retains its totipotency is the oocyte (egg). Though the oocyte, having a single set of chromosome is not totipotent. Some scientist made parthenotes by culturing eggs in such a way that it retains its double set of chromosomes and further able to make embryo (called as Virgin embryo- embryo without using sperm). Also scientist use egg having single stranded DNA in the nucleus and add another single set of chromosome in its nucleus and try to fertilize it, again fertilization without sperm. While in the process of cloning oocyte nucleus having single set of chromosome is replaced with the normal cell nucleus having double strand DNA. These all studies used egg as their source material. Unlike egg, the sperm has reduced amount of cytoplasm and its germ cell lineage lose totipotency during spermeogenesis. This infers that there is some factors in the cytoplasm of the oocyte cells which is responsible for totipotency of the cell.

Studies show that in mammalian cells, the totipotent zygote contains maternally (egg) inherited epigenetic modifiers and particular transcription factors. These, together with the embryonic transcripts, regulate development to the blastocyst stage. Deletion of some of these factors compromises development of the inner cell mass (ICM) of the blastocyst, which is pluripotent in nature.  As these cells undergo further cleavage divisions, they lose the capacity for self-renewal and turn in to multipotent cells.

PLURIPOTENT STEM CELLS

Pluripotent stem cells have ability to differentiate in many types of cells, approximately around 200 types of cells. The most common example as we all know is embryonic stem cells. Embryonic stem cells are the cells derived from blastocyst of 5 days old embryo formed by in vitro fertilization. Embryonic stem cells have many limitations in terms of ethics, religion and law. Therefore scientists have focused their research for induced pluripotent stem cells (iPS). Induced pluripotent stem cells are the cells artificially derived from non pluripotent cells like an adult somatic cells by inducing a forced expression of specific genes. These types of cells can overcome the limitation of embryonic stem cells and able to provide full benefit of it. Scientists are showing their keen interest in establishing relation of these cells in full extent with natural pluripotent stem cells. For that it is necessary to define properties, which proves the pluripotency of the cells and standardize method to prove that. At present literatures define following properties to show the pluripotency of the cells:

• Formation of a teratoma
• Unlimited self-renewal in culture
• Expression of a specific set of transcription factors (for example, OCT4/POU5F1, SOX2, and NANOG)
• Expression of a unique set of cell surface markers (such as SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81)
• Formation of embryoid bodies
• A specific pattern of gene expression assayed by whole genome profiling
• A specific epigenetic profile

According to latest work E-cadherin is the molecule responsible for giving all these pluripotent properties to the cells. E-cadherin is the intracellular glue which gives cell – cell adhesion. This is the reason for having strong adhesion between cells in blastocyst. Apart from cell glue E-cadherin is shown responsible for regulation of the genes associated with cell proliferation, cell death, metabolism of fats and sugars and translating the messages received from outside of the body. E-cadherin is also found responsible for cancer progression from benign to malignant teratoma. This finding helps us to know why embryonic stem cells have tendency of developing teratoma!

Some time the treatment of some clinical conditions may not be acceptable on the basis of social, religious, legal or ethical background by patients. In such case researchers have to stretch their thinking and work hard to find out alternate solution.

I present here one case from my experience. A 33 year old woman having infertility due to Asherman’s syndrome came to Infertility specialist for the treatment.  After not succeed with conventional treatment, she was suggested for oocyte donation and surrogacy. She was agree and accepted the option of oocyte donation but not for surrogacy.

Here clinicians and scientist stretch their thinking and figure out autologus adult stem cells could be a worth option. As stem cells are used to increase vasculogenesis in some of the heart problems like  Dilated Cardiomyopathy (DCM), Perivascular disorders etc, and here also it requires to increase blood supply in the area of endometrium. The woman was counseled for the experimental stem cells therapy as alternate to surrogacy. She gave her consent for the same. Her bone marrow was aspirated and Stem Cells were processed at StemCure and transplanted by Clinician in to her uterus. As a result of this stem cell treatment a lady has regenerated good endometrium thickness, vascularity and finally she is conceived without surrogate mother.

This opens a new window for the patients, suffering from infertility due to poor endometrium development and wants to enjoy motherhood from the day of conceiving a baby.

There is no joy for a mother in the world than talking to her baby in her womb!

Reference :  http://www.ncbi.nlm.nih.gov/pubmed

Recently I came to know about the finding that stem cells can be developed in to specific type of cell by controlling its shape. I see it as a revolutionary aspect in stem cells research though  it still require a lot work to be done and may not be available very soon for routine practice. This shows beautiful combination of two different technology and how they counterpart to each other for better prospect of humankind.

Adult autologus stem cell treatment is the most promising treatment in coming days for many diseases which are not responding well to conventional medicinal therapy.  These cells are cultured and differentiate in to various lineages for their application like Mesenchymal cells, osteoblasts, chondrocytes etc. Normally this is done with the help of biochemical moiety. This innovative research suggests a new technique of culturing and differentiating the cells with the help of scaffold and based on the shape of the cell instead of biochemical moiety. This may provide a good alternate to expensive and very temperature sensitive biochemical substances used in culture on the cells.

The current technique of adult cell culture is used for more than decade and so far there is no incident is reported for its hazardous effect, even though some researchers are worried about the effect of biochemical substances on developing cells. This technique would be able to waive their doubt.

This has definitely initiates a new trend in tissue engineering as morphology of the cell can be used for differentiation of the cells. Evaluation of various types of scaffold made using various types of material and technology for particular lineage of the cells. Nanotechnology already proved its wide application in various field including medicine. Now it is going to prove its imminent existence in the field of tissue engineering and bio technology.