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Stem cell therapy

Dr.Shobhana Mohandas. MD. D.G.O..FICOH  (Dip Endoscopy)Dept of Infertility and Key hole surgery

Sun Medical Centre, Unit of Trichur Heart Hospital, Thrissur

 

 

 

Stem cells are primitive cells that give rise to other types of cells.  Cell therapy using stem cells is a group of techniques, or technologies, that rely on replacing diseased or dysfunctional cells with healthy, functioning ones. These new techniques are being applied to a wide range of human diseases.  The commonest stem cell therapy that the physician is familiar with is bone marrow transplant.   Cord blood being a rich source of stem cells, there is increasing interest in the storage and use of cord blood as a source of stem cell therapy.    Embryonal stem cells, derived from the human embryo is a more versatile type of stem cell, and amidst ethical problems and technical problems regarding the delay in culturing a cell line, is another source of stem cell, which is being sought for, in stem cell therapy.  The use of cord blood and human embryos for this therapy brings the gynaecologists into focus as potential helpers in providing these sources of stem cells. 

What are stem cells?

Stem cells are special types of cells having remarkable ability for self-renewal and they remain undifferentiated for indefinite periods of time, remaining as “reserve” cells in the body.

Types of cells in the body:

 Totipotent cells are considered the "master" cells of the body because they contain all the genetic information needed to create all the cells of the body plus the placenta. Human cells have this capacity only during the first few divisions of a fertilized egg. After 3 - 4 divisions of totipotent cells, there follows a series of stages in which the cells become increasingly specialized.

Pleuri potent cells are a result of the next stage of division.  These are highly versatile and can give rise to any cell type except the cells of the placenta.

Multipotent cells are at the next stage, meaning they can give rise to several other cell types, but those types are limited in number. An example of multipotent cells is hematopoietic cells—blood stem cells that can develop into several types of blood cells, but cannot develop into brain cells. At the end of the long chain of cell divisions that make up the embryo are "terminally differentiated" cells—cells that are considered to be permanently committed to a specific function.

Difference of stem cells from other cells in the body:

The other types of cells in the body are adult somatic cells, germ cells and embryonic cells.  The difference between adult somatic cells and stem cells is that, adult somatic cells, once differentiated, cannot change their speciality,e.g., adult liver cell cannot perform the function of an adult pancreatic cell.  Stem cells divide but do not differentiate or specialize unless directed to do so under specialized environments either “in-vivo” or “in vitro”.  

Types of stem cells: Two types of stem cells have been identified.

1.        Adult somatic stem cells, which can be unipotent or multipotent.

Unipotent cells are those, which are capable of repairing or regenerating the tissues or organ in which they exist.  

Multipotent stem cells are those that can differentiate into cells within the same family.  For e.g., Haemopoetic stem cells can form all blood cells like RBC, WBC, Platelets, but not liver cell.   Haemopoetic stem cells, bone marrow, mesenchymal stem cells, neural stem cells, skin stem cells, etc are examples of adult somatic stem cells. 

2.        Embryonic stem cells, which are pleuripotent.

 

Uses of stem cells:

Stem cells are being tried in a variety of conditions.  Many of the indications for which they have been used have undergone controlled studies and many others are still under investigations as conditions, which possibly could benefit from stem cell therapy.  Stem cell research is coming up in a big way in India and quite a few workers have started using stem cells for a variety of indications.  Long-term effects of these therapies are yet to be published. 

Haematologic malignancies:

Since the 1980s, human hematopoietic stem cells have been isolated from bone marrow and used to treat patients with various hematologic malignancies. Bone marrow transplantation also has been used successfully to treat immune deficiencies, hemoglobinopathies, and metabolic diseases. Hospitals in India treating Bone Marrow Transplants are; Manipal Hospital (Bangalore), Apollo Hospitals (Chennai) and Indraprastha Apollo Hospital (New Delhi).

Myocardial infarction and other cardiac conditions:

 Stem cells are delivered to the heart through an intracoronary catheter. Once the stem cells have reached areas of infarcted myocardium, they may improve contractility by differentiating into functional cardiac myocytes and improve perfusion by releasing cytokines that induce angiogenesis.  The results have been positive in certain trials and without effect in others. In some patients, newly developed zones of myocardium have developed intrinsic electrical activity that spurred malignant ventricular arrhythmias, requiring placement of an implantable cardioverter defibrillator.

 In India work in this area was pioneered at All India Institute of Medical sciences, Delhi.  Many patients with this conditions are being given stem cell therapy in Asian Heart Institute & Research Centre, NiCRM, Nizam's Institute of Medical Sciences (NIMS) , Frontier Lifeline Hospital, Chennai, Tirupati-based C Venkateswarlu Institute for SCT,  & Manipal Education and Medical Group's (MEMG).  Phase I multi-centric clinical trial using bone marrow mononuclear cells on acute myocardial infarction are going on at five hospitals in the country, that is, CMC; Sanjay Gandhi Post Graduate Institute for Medical Sciences (SGPGIMS), Lucknow; Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh; Research & Referral Hospital, New Delhi; Air Force Medical College (AFMC), Pune and All India Institute of Medical Sciences (AIIMS), New Delhi. 

Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis, Spinal injuries:

Animal studies have found stem cells useful in neurological diseases.   Adult stem cells from bone marrow or adult tissues, without viral contamination could be used for this.  If embryonal tissues are used, it should be less than 14 days old prior to formation of neural tissue.  Stem cell therapy for paraplegics following spinal injury is being done at Global hospital, hyderabad as an ICMR project.  . The pilot study on acute ischemic stroke has also been initiated at AIIMS.  Reliance Life Sciences, Mumbai has characterised 10 stem cell lines, including two neuronal cell lines, dopamine producing neurons and neurons for patients of stroke. 

Disorders of the eye: In one of the programmes at L V Prasad Eye Institute (LVPEI), Hyderabad, limbal stem cells are being used to repair the cornea surface.    

Paediatric conditions: Fanconi’s anaemia and some metabolic disorders have successfully been treated using cord blood stem cells.  Cord blood is more readily accepted for paediatric cases as compared to adult patients.  This is because, children have a  smaller physical size and the stem cell dose will be smaller and easily available from the cord units even if the number of stem cells present in them are limited. 

Others: stem cell therapy holds promise for many other conditions like type-1 diabetes, burns,and research is being done on stemcells  to produce sperms, obviating the need for sperm banks.  

Sources of stem cells:   

Adult stem cells (AS): Hematopoietic stem cells are present in the bone marrow and circulating blood. These cells are readily accessible. Other rare, hard to identify AS cells are scattered throughout the body.  Stem cells from bone marrow take 3 weeks to culture. 

Cord blood stem cells: Normally, cord blood is collected before the placenta is delivered. A baby's umbilical cord blood, which is otherwise discarded, is a rich source of stem cells endowed with the ability to regenerate and replace a variety of tissues.  In recent years, the concept of cord banking is catching on in India. Interestingly, banking cord blood in a cord blood bank is considered a "biological insurance" since the child from whose umbilical cord the blood is collected can ostensibly stand to benefit from it at any stage of his life. We however do not have enough cord blood banks that have stored blood for more than 20 years or so and so it remains to be seen if such blood can be used life-long. We have to see whether cell lines can be maintained so long keeping their inherent capacity to function as stem cells intact.

  There are blood banks which offer to store baby's cord blood in liquid nitrogen for a period 21 years for a fee of around Rs.60, 000. The Chennai-based Cryocell has set up facilities to preserve cord blood. Similarly, Life cell, yet another private stem cell bank in Chennai says that about 1,000 expectant parents have enrolled to bank the cord blood stem cells.  The recently-set up Bangalore-based Cryostem Karnataka Pvt Ltd is a cord blood stem cell bank as well as research centre. The other cord blood banks in India are Reliance life sciences, Mumbai,and  Asia life cell Pvt Ltd, Chennai,.

The Cord Blood Stem Cells (CBSC) is derived from the umbilical cord of consenting mothers. Cord blood is collected from the part of the cord attached to the placenta after the baby has been separated.  The blood is collected in bags resembling blood collection bags.  It can then be sent to appropriate centers after labeling. 

The pure stem cells are then separated from the rest of the cord blood with a patented technology, and are cryogenically frozen in vials, under strict laboratory conditions. These Cord Blood Stem Cells are pure, with no red or white cells. This negates the need for blood typing or HLA matching, safe, with no graft versus host or rejection issues (as is the potential from whole cord blood).  Pluripotent, CBSC have been proven to regenerate every single cell in the human body. (C. Verfaillie, Univ. of Minnisotta July 2002). 

In most cases, Cord Blood Stem Cells Therapy involves one simple IV (intravenous) injection.  Once in the body, the cells migrate to the site of disease and begin replacing damaged or missing cells. This process of noticeable reconstitution usually peaks between 3 and 6 months following treatment. Often significant results are noted at the one-month mark.  Cord blood is a reasonable graft source for adults who cannot find an HLA match in a bone-marrow registry or who need transplantation sooner than the 3–4 months needed to obtain unrelated adult-donor bone marrow.

Embryonal stem cells (ESC): Embryonal stem cells are pleuripotent. 

Embryonal cells can be taken from the inner cell mass(ICM) of the blastocyst around days 5–6 after fertilization in mouse and days 8–9 in humans, isolated and put in culture. The trophectoderm is removed and the inner cell mass (ICM) is plated on to a feeder layer of mouse or human embryonic fibroblasts, which is essential for the survival of the ICM. The ICM then flattens into a compact colony of ESCs, which is than mechanically dissociated and re-plated several times to give rise to stable cell line. When cultured in the laboratory, human ESCs grow as compact colonies and usually require the presence of feeder cells for their survival. When undifferentiated human ESC colonies are detached from the feeder layer and transferred into serum containing medium, they form multi-cellular aggregates called embryoid bodies (EB) which can contain cell types representing all three germ layers of the body: endoderm, mesoderm, and ectoderm.

Somatic cell nuclear transfer: Human ova are denuded of their neucleus and the neucleus from a patient’s cell is transferred in to the ovum.  It develops into an embryo and the inner cell mass is taken from its blastocyst and stem cells cultured from it.  This method has the advantage of using the patient’s own cells with no potential of immune rejection and the stem cell being genetically identical to cell source.  People who believe that life starts before conception are against the idea of growing human embryos and destroying them, because human embryos according to them could be potential human beings.

Disadvantage:  Culturing human embryonal stem cells can take up to 6 months and it may be too long a period for critically ill persons who are looking up to stem cell therapy as a last resort therapy.   

Stem cell therapy and the gynaecologist

The gynaecologist, especially in charge of IVF centres could be approached for embryos or ova, which could be cloned to form embryos, which are a source of pleuripotent stem cells.  Obstetricians could be approached by cord blood banks to make people more aware of the advantages of storing their baby’s cord blood, which could be used any time in the next 20 or so years, should the baby face the contingency of suffering from any haematologic/metabolic condition requiring stem cell therapy during that time.  Women with history of relatives suffering from such conditions could approach the obstetrician with a request to store the cord blood of her baby. 

Stem cell nuclear transplant or cloning of ova is still controversial as many people find it repulsive to manipulate potential human beings for research even if they are in the embryonic form.  Culturing embryonal cells take a long time and till this period is shortened, using embryonal cells to form useful stem cells for therapy should be considered a research project as far as humans are concerned.  Animal studies have been encouraging. 

Storing cord blood is very costly and is at present feasible only for affluent families.  Whether the cell lines can be maintained for a long time and whether any patient could benefit from it after 20 years is yet to be seen.  Except for haematologic/metabolic syndromes, at present, the baby whose cord blood is being stored can have no other use for it as research stands today.  Use in juvenile diabetes is another potential use, but as of now, it is still futuristic. 

Cord blood of the baby could be used for many conditions like cardiac conditions, neurologic conditions etc of close relatives/acquaintances if the parents desire to donate it for such purposes.   

Conclusion; Storing cord blood is today being done with finances provided by the mother delivering the baby.  Thus it is difficult for an obstetrician to be highly proactive and ask all patients to store their baby’s cord blood.  However, the media being very active about propagating information about the uses of cord blood, every obstetrician should know the centres with cord blood banks and the method of collecting, storing and dispatching cord blood to such centres. 

 

 

 

 

 

 

 

 

 

 

 


 

 

 

 

 

 

 

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