A new phrase of optimism has entered the global vocabulary over the past two decades: ‘regenerative medicine’. Today, everyone seems to be interested in what life-enhancing products the field might yield.
Expectations are high, but the time frame for delivery remains speculative. This is because the term ‘regenerative medicine’ includes an array of projects, some with short and straightforward paths to market, and some with difficult and uncertain roads to success.
The field spans from the use of advanced technology to discover new drugs, to new biological agents focussed on tissue repair. Importantly, it also includes stem cell therapies for tissue replacement.
All of these technologies are evolving rapidly in laboratories around the world. Predictions that regenerative medicine will quickly become a US$20 billion (A$22.4 billion) industry are now common. The U.S. government is tracking 2,496 clinical trials of stem cell-based medicines, and several biotechnology companies are becoming recognised for their work in the field.
Currently Geron Corp in San Fransisco is working with the U.S. Food and Drug Administration to begin the first U.S. clinical trial using cells derived from embryonic stem cells. They will be using oligodendrocytes (a type of cell in the central nervous system) for spinal repair. Geron has also partnered with General Electric to commercialise cellular assay products derived from embryonic stem cells for use in drug discovery, development and toxicity screening.
And the biopharmaceutical company Athersys in Cleveland is using a bone marrow-derived product that can control inflammation. The company has partnered with Pfizer for treatment of inflammatory bowel disease. Celgene in New Jersey has used extracts of the human placenta to create cell products that treat Crohn’s disease.
And these examples are just in the United States.
The emergence of cell therapeutics has much to do with the vision of scientists working to understand the biology of normal development and the opportunity to study the very early cleavage stage embryo as a result of research and clinical application of in vitro fertilisation (IVF). The California Institute for Regenerative Medicine (CIRM) was born on the optimism of some of these cell biologists and patient advocates of the therapy, and in spite of the ideological intransigence of former U.S. President George W Bush. Californian voters, in a citizen-initiated referendum, backed Proposition 71 in 2004 and created CIRM, which now provides US$3 billion (A$3.4 billion) in support of stem cell science and regenerative medicine.
The creation of CIRM galvanised other countries and states to support regenerative medicine. CIRM has a strong portfolio of collaborative partners – Britain, Germany, Spain, Japan, Canada, China, and the state of Victoria in Australia as well as the U.S. states of Maryland and New York. The world is now interlinked in our endeavours to deliver a major new medicine.
So what may we expect to happen over the next two decades? Most of the current clinical trials involve adult autologous (a medical term in which donor and recipient are the same person) cell therapies – using stem cells taken from the patient’s own bone marrow or fat tissue. These are sometimes altered slightly, often expanded in number outside the body and then replaced in the patient.
Also in the pipeline and hopefully headed for clinical trials, are autologous cells corrected using gene therapy or therapies.
This involved induced pluripotent stem cells (iPS) – cells derived from banked embryonic stem cells, or even adult cells, which have been reprogrammed to behave like embryonic cells.
CIRM, like many of the world’s leading stem cell research centres, is supporting a new cadre of academic–commercial teams, linked where appropriate, to the best scientists around the globe and pursuing that next tier of stem cell derived therapies. Their goals are emblematic of the field as a whole. They won’t all succeed, but we expect a significant number of these projects to result in clinical trials in two to five years.
World opinion is moving strongly in support of regenerative medicine. In Melbourne, stem cell and immunology scientists are leading the way with the largest number of collaborative projects with California. This is due to the strong innovative vision of the Victorian government and the ambition and status of Melbourne scientists to rise to the occasion and establish collaborations with overseas academics and biotech companies that are at the forefront of the regenerative medicine revolution.
The optimism centred on the field of regenerative medicine is well founded. It just needs to be tempered with a bit of patience and the knowledge that while many paths to therapies will get to their target, most will not be a straight line – and many will require multiple attempts to get to the ultimate therapeutic goal.
In the pipeline
Here are some of the breakthroughs that scientists hope to achieve over the next 20 years:
- Genetically modifying haematopoietic (blood) stem cells from HIV/AIDS patients to result in cell-level resistance to HIV infection.
- Targeting sickle cell disease, again using haematopoietic stem cells, modified to have the normal gene inserted instead of the disease-causing gene.
- Using the homing characteristics of neural stem cells to destroy inoperable glioma brain tumours. The neural stem cells can be loaded with cell-killing molecules that target the tumour directly.
- Destruction of cancer stem cells that cannot be destroyed by chemotherapy or radiotherapy. Many of these have protective molecules, and by blocking these molecules scientists could make them vulnerable to treatment.
- Directing embryonic stem cells to differentiate into pancreatic islet cells, so that they can be placed under the skin of Type 1 diabetes sufferers. These cells are glucose responsive and will keep the diabetic patient stable. They are easily imaged and replaced.
- Grow retinal epithelium from embryonic stem cells on appropriate scaffolds and insert these into the eyes of patients with dry macular degeneration.
- Develop neural and glial precursor cells for the treatment of strokes and other conditions. These cells can be derived from embryonic stem cells and delivered to the central nervous system.
- Treat the disease Epidermolysis bullosa that results in the loss of the outer skin layer. Scientists are planning to convert a patient’s skin cells into iPS cells, insert the correct gene and then direct the cells to grow into epidermal sheets that can be transplanted into the patient.