Cell Guidance Systems Blog

Extracellular proteins and glycosaminoglycans (GAGs) within the extracellular matrix (ECM) undergo limited enzymatic cleavage to release fragments which exert biological activities that are distinct from their full-length progenitors. These fragments regulate a range of processes including angiogenesis, inflammation, wound healing and fibrosis and have been implicated in many diseases including neurodegeneration and cancer.

Just like people, cells can take a while to adapt to a new environment. For cells cultured in-vivo, its possible to wean cells on to new conditions. However, when cells are implanted, moving from in-vitro to in-vivo conditions, weaning isn’t an option. The resultant culture shock can kill most of the transplanted cells.

3D bioprinting enables the production of cell-laden models in which cells, biomolecules and biomaterials are deposited in a spatially predefined 3D position. As 3D bioprinting capabilities become more sophisticated, the potential to fabricate functional tissues and organs for drug testing and transplantation is being realized. But with simple stem cell procedures costing $5,000 to $50,000, how many will be able to afford these innovations?

Just a decade ago, for the millions of people living with rare genetic diseases, there seemed little hope that an effective treatment could be developed. One of the main obstacles is the massive costs of drug development; for many rare genetic diseases, there aren't even enough patients to conduct a formal clinical trial. But changes to the regulatory framework and the development of gene therapy platform technologies that, once proven safe, may be rapidly turned to a wide number of disparate diseases, is offering hope.

The use of extracellular vesicles for regenerative and therapeutic applications is gaining currency. Notably, exosomes derived from mesenchymal stem cells (MSCs), have garnered attention. However, even manufacturing exosomes for relatively small-scale, preclinical and clinical activity has proved challenging. How will scalable production of vast quantities of exosomes for routine therapeutic use be achieved?

Immunomodulatory drugs, such as Immune-checkpoint inhibitors (ICIs) have transformed cancer care. However, as with other cancer drugs, ICIs are associated with significant adverse events which can even be fatal. How do these occur and what is being done to reduce their severity?

Since the 1986 approval of Muromonab, the first therapeutic monoclonal antibody (mAb), used to treat steroid-resistant transplant patients, mAbs have rapidly evolved and gained clinical ground become the largest class of biopharmaceuticals. During this period, mAbs have garnered a reputation for safety, favourable PKPD, and high levels of specificity that have made them a preferred drug modality in many therapeutic applications.

Antimicrobial resistance (AMR) is on the rise. By 2050, AMR may be killing more people than cancer does now. Already, the mortality rates and economic impact are alarming. According to the Centre for Disease Control the total cost of AMR in the USA is estimated at $55bn and results in over 35,000 deaths each year. The worldwide death toll is ticking over 700,000.

Little more than 10 years ago, the prospects for gene therapy were bleak. Early clinical trials had served to highlight the risks. In particular, the 1999 death of Jesse Gelsinger proved a turning point, and clinical progress stalled for years. The risks are now better understood and controlled, and in recent years so much has changed. The FDA's 2017 approval of the first human gene therapy drug, Luxurna, heralded a new era with a further twenty gene therapies approved by 2019 with 1000 more in clinical trials.

16 years on from the groundbreaking development of induced Pluripotent Stem Cells (iPSCs), the scientific community has generated an explosion of applications in the areas of high throughput drug discovery and developmental biology research. Personalised regenerative medicine and cell-based therapies are also on the horizon. But after all these years, iPSC-based therapy remains in its infancy. What are the future prospects?