The rapid strides in technology are revolutionizing virtually every area of human endeavour. Though applied health care research and development is one of the late entries in the technology bandwagon, it is picking up at a frenetic pace after the unveiling of human genome. Several vistas have opened up and scientists are working round the clock to crack the code and unveil some life saving and cost effective solutions to the numerous scourges, that man is being infested with at an increasingly alarming rate.
Scientists of India are actively involved in several key health care projects which are attempting to harness the technological developments in various fields. This is being witnessed sporadically at various centres in our country most of which happen to be in the Southern regions of India.
India is now becoming the premier location for health care and host to internationally acclaimed technology institutions like Indian Institute of Technology, Council for Scientific and Industrial Research, Central leather Research Institute amongst others is beginning to become an ideal platform for this exciting research. Given the right encouragement from the government, India would play a key role in these developments. Some of the applied healthcare projects involving cutting edge technology are detailed here.
Biotechnology: Stem Cells research
One of the most promising areas in basic research today involves the use of stem cells. These unique cells have the capability to transform and replenish the different tissue types that make up the body, and they also represent the fundamental building blocks of human development.
In general, stem cells can be divided into two broad categories: adult (somatic) stem cells and embryonic stem (ES) cells. The recent derivation of human ES cell lines from human blastocysts and human embryonic germ (EG) cell lines from primordial germ cells has aroused intense public and scientific discussion. This interest stems in part from the controversy surrounding the origin of these lines but, more importantly, from the widespread conviction that their availability will have a major impact on several scientific areas including cardiac research and clinical cardiology.
Heart attacks and congestive heart failure remain among one of world's most prominent health challenges despite many breakthroughs in cardiovascular medicine. Despite successful approaches to prevent or limit cardiovascular disease, the restoration of function to the damaged heart remains a formidable challenge. Recent research is providing early evidence that adult and embryonic stem cells may be able to replace damaged heart muscle cells and establish new blood vessels to supply them.
The destruction of heart muscle cells, known as cardiomyocytes, can be the result of hypertension, chronic insufficiency in the blood supply to the heart muscle caused by coronary artery disease, or a heart attack. Despite advances in surgical procedures, mechanical assistance devices, drug therapy, and organ transplantation, more than half of patients with congestive heart failure die within five years of initial diagnosis.
Research has shown that therapies such as clot-dissolving medications can reestablish blood flow to the damaged regions of the heart and limit the death of cardiomyocytes. Scientists now know that under highly specific growth conditions in laboratory culture dishes, stem cells can be coaxed into developing as new cardiomycytes and vascular endothelial cells.
We are interested in exploiting this ability to provide replacement tissue for dead or impaired cells so that the weakened heart muscle can regain its pumping power. This approach has immense advantages over heart transplant, particularly in light of the paucity of donor hearts available to meet current transplantation needs.
Stem cells in neurological disorders and mentally retarded children:
Using animal models, scientists have coaxed stem cells into becoming nerve cells, myelin sheaths that surround the nerves, and nerve cells into becoming muscle cells. Adult neural stem cells (NSCs) have the ability to differentiate into vascular, endothelial, smooth muscle and neural lineage invitro and invivo. In regenerating damaged neural tissue, NSCs may contribute to both neurogenesis and vasculogenesis, resulting in cooperative organogenesis. Amazingly, some stem cells seem to go preferentially to injured tissues when introduced in an animal.
This principle of stem cells holds a significant promise for discovering effective therapeutic modalities for several neurological diseases which have hitherto eluded all human efforts. Those diseases where cells are damaged or malfunctioning, and might be replaced are especially amenable - for example, Parkinson's disease, juvenile diabetes, stroke, spinal cord injuries and mental retardation in children due to various causes. Stem cell research offers feasible modalities of replacing damaged neuron with healthy cells and reverse the ravages of the neurological diseases (e.g. Alzheimer's disease) as opposed to just slowing their progression. Besides directly replacing damaged organs and tissues, there are other potential uses for stem cells. Pharmaceuticals, for example, could be screened on cultures of stem cells in the laboratory.
Traditionally, leads from plant sources and synthetic chemistry had been the starting points for drug discovery research. Through hit and trial methods involving plant resources had given us significantly important therapeutic molecules. Conventional synthetic chemistry, on the other hand, had not been quite effective considering the amount of cost and resources involved. The stage of finding the prospective candidate drugs has become a major bottleneck in the pharmaceutical research and development all over the world. Over the last few years, the number of new chemical entities (NCEs) successfully entering the markets has become a trickle, even for research based global pharmaceutical giants.
Centuries of biomedical research have so far managed to unearth drugs targeting only about 500 gene products. Critical Bioinformatics technologies, conversely, have opened up floodgates of drug targets within a decade of their initiation. The completion of the human genome has thrown up an estimated 30,000 to 40,000 genes for drug discovery research and this is just a beginning.
Cardiovascular research has numerous areas for active exploration using Bioinformatics methodologies. Several promising approaches are being pursued for the treatment and prevention of ischaemic heart disease. Identification of genes and gene clusters responsible for various congenital heart diseases would give vital leads for gene therapy. Functional genomics, proteomics and gene regulatory networks would help immensely in narrowing down the potential drug targets. Bioinformatics modeling softwares would then assist us in testing the efficacy and toxicity of these, insilico as against invivo studies. In addition to culling out a large number of candidate drugs, the reductions in cost and manpower requirements with such rational drug design assumes stupendous scale vis-à-vis traditional approaches.
Modeling the heart
In post myocardial infacrt patients, infarcted cardiac muscle does not regenerate and it is replaced by fibrous tissue, which does not stand the pressure as good as cardiac muscles. This weakened cardiac muscle can't sustain the wall tension and, as per Laplace's law, the ventricular volume keeps increasing. This results in a vicious cycle deteriorating the cardiac function. The cardiac re-modelling methods aim to break this cycle and thereby keep he LV volume in check.
In graded steps, data from various diagnostic modalities is used to build computer models of different types of heart cells, and, ultimately, an accurate 3-D computer model of the ventricle. With refined computational calculations and techniques, the model will simulate ventricular fibrillation. These scaled models would give us a thorough understanding regarding the focus of arrythmias and would lead to more focused therapeutic approaches as against the potentially damaging external defibrillator using electric shocks.
Modeling technologies are also being studied for designing artificial heart valves and other implants. The reason for the failure of stented tissue valves is the distribution of stress to the sutured areas. For effective long term functioning with minimal complications, the valve implants should be able to mimic the native valves as closely as possible. CAD/CAM techniques are being employed to achieve this objective.
Bioprosthetic heart valves and Material Science
Broadly, there are three basic types of heart valves. Mechanical valves, which are prone to thromboembolism belongs to the first category. The patients with these valves need to be put on a oral anticoagulation maintenance therapy which has its own attendant bleeding complications requiring careful vigilance and monitoring.
Second are the stented tissue valves of Bovine or Porcine origin and third category is the homografts. These two categories, known as bioprosthetic heart valves, have proven clinically successful over short term, but long term performance has been disappointing. The degenerative failure of these bioprosthetics results mainly from severe calcification and from leaflet tearing. The other disadvantages are limited availability, antigenicity and degeneration. The other disadvantages are limited availability, antigenicity and degeneration. However, the advantage of not having to be on life long anti-coagulation far outweighs these disadvantages. Researches are working around the world to obviate these disadvantages.
Though our country's cardiovascular R&D produced few mechanical heart valves, Chitra valve being more prominent, we still have not succeeded in producing a state of the art Bioprosthetic valve. The cost of imported prosthetic valves range from Rs.45,000/- to Rs.60,000/- which makes it an impractical proposition for our country. Developing a suitable, cost effective, safe and durable bioprosthesis valve and marketing it on a national scale is absolutely important given the prevalence of mitral stenosis and other valvular heart diseases in India.
Biomaterials research
Various studies and research is being conducted in the area of Biomaterials in collaboration with Central Leather Research Institute, Chennai to develop Bioprosthetic valves. As the supply of xenografts is subjected to potential limitations, Scientisists are exploring options of developing collagen as a scaffold on which autologous cells would be layered.
Injectable collagen can be engineered to form intravascular stents during coronary angioplasty in place of hugely expensive mechanical stents. Impregnation of drugs like, restenosis preventing Paclitaxel and Rapamycin; and anti-platelet aggregation agents like clopidogrel in the injectible collagen medium would ensure minimal long term complications. In addition, coating the intra luminal wall with normal host endothelial cells would prevent thrombosis. Most importantly, this would cost about Rs.1000/- as against Rs.1,20,000/- for a drug eluting stent imported from abroad.
It is huge challenge to meet the health care costs of ever burgeoning population. There is an urgent need to invest and encourage the applied research in health care involving technology. This becomes all the more important in a cost intensive health care area like cardiac health care.
- (The author is with Bio Medical Informatics, IIT Allahabad)