CNV1-I1-5-Life Sciences

BACKGROUND

For centuries, scientists have known that certain animals can regenerate missing parts of their bodies. Humans actually share this ability with animals like the starfish and the garden lizard. Although we can’t replace a missing leg or a finger, our bodies are constantly regenerating blood, skin, and other tissues.

WHAT ARE STEM CELLS?

Regenerative Medicine is a new way of treating diseases, using human stem cell-based therapies. They have the potential, which most molecular medicines for chronic conditions do not have, of returning the patient to health with respect to that condition. The identity of the powerful cells that allow us to regenerate some tissues was first revealed when experiments with bone marrow in the 1950s established the existence of stem cells in our bodies and led to the development of bone marrow transplantation, a therapy now widely used in medicine, for treatment for several blood diseases.

Stem cells are unspecialized “master” cells in the human body having a unique capacity to multiply and differentiate into many types of specialized cells and tissues.

Stem cells exist at all stages of human development from early embryos to fetuses to adults. In general, there are three types of stem cells: embryonic, fetal and adult. Embryonic stem cells, although very versatile, continues to face ethics related controversies. Stem cells can be found hidden in practically all organs of an adult, in all fetal tissues and also in the embryo. Currently, ethical and scientific issues surround both embryonic and fetal stem cells hinder their widespread clinical implementation. In sharp contrast, stem cells recovered from tissues immediately after the birth of a new born, namely from the umbilical cord, the umbilical cord blood cells, amnion/placenta, umbilical cord vein, or umbilical cord matrix cells are easier to get, and do not have any ethical issues. These are readily available sources of cells that are capable of forming many different cell types. This capability of the cell to form different tissue types is referred to as multi-potentiality of cells.

Compared to traditional medicine, Regenerative medicine (RM) uses a new concept of regeneration by exploiting the regenerative potential of stem cells for replacing or repairing tissues or organs that are affected by disease, trauma or aging. While the present medical therapies focus on the pathobiology of the illness, elimination of cell death, and tissue protection, regenerative medicine attempts to stimulate the body’s own natural healing processes by activating its inherent ability to repair and regenerate.

With increasing demand and focus to launch newer and advanced curative solutions, stem cell therapeutics has generated a lot of excitement and debate. After a decade of experimentation, it has now become increasingly clear that realization of this intuitively logical concept is far more complex than originally envisaged. The scope of regenerative medicine extends much beyond the simple paradigm of providing new building blocks to a failing organ, to processes that dynamically alter the molecular landscape within the tissue via a number of paracrine factors and other multiple potential reparative processes. Thus, this discipline employs the use of at least three components namely the cells, an extra cellular matrix to support the cells (i.e. a scaffold), and cell communicators (or signaling systems) either alone or in combination. This discovery raised hope in the medical potential of regeneration.

For the first time in history, it became possible for physicians to regenerate a damaged tissue with a new supply of healthy cells by drawing on the unique ability of stem cells to create many of the body’s specialized cell types.

STATUS OF RESEARCH

Stem cell research is being pursued in the hope of achieving major medical breakthroughs. Scientists are focused on creating therapies that rebuild or replace damaged cells with tissues grown from stem cells and offer hope to people suffering from cancer, diabetes, cardiovascular disease, spinal-cord injuries, and many other disorders. Both adult and embryonic stem cells may also provide a route for scientists to develop valuable new methods of drug discovery and testing. They are also powerful tools for doing the research that leads to a better understanding of the basic biology of the human body. All institutions and medical establishments are aiming to invest in this research knowing its potentials. Most academic institutes in India have some semblance of a stem cell laboratory and are making efforts to invest in research and training.

The past and ongoing endeavor by researchers, policy makers and corporate aims at cultivating transparency and adopting well-regulated stem cell research programs. This is very important to avoid placing false hope on stem cells’ capabilities and allow usage only after you prove its efficacy through well designed experiments in the laboratory and the clinic. An inclusive and progressive policy will accelerate progress towards new stem cell based treatment by initiating discussion among leaders in ethics, public policy, health care industry on how to meet the several challenges of this upcoming field.

Studies on safety and efficacy in disease models of small animals have demonstrated universal benefit following delivery of a diverse repertoire of stem cell phenotypes, despite a huge variation in dosage, the timing and site of delivery. Such proof-of-principle opens avenues for future optimization of this novel stem cell platform for translation into clinical practice in addition to being a model for drug discovery and development. This transition from a stable stem cell phenotype into reproducible and efficacious products involves extensive process validation, robust quality systems and a strong package of laboratory data and preclinical data on animals. None of these are cheap and the challenge lies with us to deliver a new generation of cost effective and efficacious therapeutic solutions.

Molecular biology techniques have reached newer heights. In keeping with that, Genomic and proteomic evaluation of adult stem cells will throw more light on the actual pathways through which cells work; this can give a lead to small molecule development for the future, help in companion diagnostics, and make theranostics very significant.

Such approaches would move naïve “first generation” stem cells from achieving a specific limited therapeutic objective to another level of understanding delivery, evaluation of the risks and benefits of repeat therapy and use of well characterized, lineage specified stem cells, transplanted either alone or in combination. This will mark the beginning of “second generation” therapeutics

CHALLENGES FACED

Over 50 years have passed since the discovery of hematopoietic stem cells, almost 20 years since the discovery of human embryonic stem cells (hESC), and 10 years since the discovery of induced pluripotent stem cells (iPS cells). There are also 5,000+ stem cell trials ongoing in clinics globally. Despite this experience, what do we know about the safety and efficacy of stem cell therapeutics? In the increasingly complex stem cell space, it is a timely question to ask, because the regulatory assessment criteria designed for conventional medicines are not directly applicable to stem cell therapy.

Although clinical trials of stem cell therapy have been criticized by a few as being premature, there is no substitute for the human model as stem cell therapies enter the era of translation.

Thus, the challenges faced by researchers are many; important of them are absent regulations, too much of interference from various agencies, non availability of finances, lukewarm governmental support, complex process of getting approvals, cost of reagents, cost of trials in humans, confusing role played by multiple agencies, cost of import of technology etc.

It is well known that the pace of medical and scientific advance is gaining significant momentum, but the travel from the bench to the bedside, takes its own time, resources and patience. Close collaboration among multiple disciplines alone will define success. With more and more new cell type under development, the present challenges faced by this industry and the regulatory expectations are only increasing. Thus, we have miles and miles to tread. Although clinical trials of stem cell therapy have been criticized by a few as being premature, there is no substitute for the human model as stem cell therapies enter the era of translation.

There are currently more than five thousand clinical cell based trials world over, and some favorable reports are trickling in. Even though the feasibility and safety of stem cell use has been reasonably established in these trials now, the superior efficacy of stem cell therapy is yet to be proven in large multi centric human trials.

THE FUTURE

With the market size expected to touch the US$ 250 plus million mark by the end of this decade, stem cell based therapies will be a major component of the new era medicine. When results expected are significant, let us not dwell on the enormous cost implications. Going by the results of the experiments from all corners of the globe, stem cell medicine and tissue engineered based stem cell devices will find a major place in medical prescriptions in the next 5-10 years’ time frame. With a cohesive Govt. initiative and appropriate funding, within 20 years, regenerative medicine will be the standard of care for replacing all tissue/ organ systems in the body, in addition to it’s extensive industrial use for pharmaceutical testing. In the next two decades, we also hope to achieve major milestones starting with insurance reimbursable regenerative therapies, and establishment of standards for the regulatory approvals.

We also expect that the world will engineer smart degradable biocompatible scaffolding and develop micro-fabrication and nanofabrication technologies to produce tissues with their own complete vascular circulation, producing an in vitro sophisticated 3-D tissue and organ models that cannot be ordinarily regenerated through routine in vivo techniques. Just as discovery and usage of penicillin was the inflection point in the fight against infectious diseases, application of stem cell based therapies will be the turning point in the treatment of hitherto inadequately treated or incurable diseases of the twenty first century. It is painful to recognize that the life style diseases are on the increase and we hope stem cell therapy could become a standard of care for such disorders like Diabetes, Parkinson’s disease, Peripheral vascular disease, Motor Neuron disease, to list a few.