Cells constantly exchange material with their surroundings. At one end of the ingestion scale, nutrients are adsorbed by mechanisms such as endocytosis. At the other end, entire cells can be swallowed by another cell. Terms such as entosis, emperitosis, phagoptosis and, simply, cannibalism, describe these fascinating phenomena.
Exosomes possess an exceptional ability to target specific cells and deliver a highly heterogenous cargo reflective of the type and physiological/pathological conditions of the cell that produced them. Both exosomes and interleukins are critical cellular messengers for the modulation of cellular functions. In recent years, the important role that interleukins within circulating exosomes play in disease and normal tissue homeostasis has become clear.
Great strides have been made in recent years in treating some cancers, such as melanoma. But despite huge efforts, little progress has been made in improving the odds for pancreatic ductal adenocarcinoma (PDAC). 95% of individuals receiving a diagnosis of PDAC survive less than 18 months. It is the worst prognosis of any cancer, making it set to be the second biggest cause of cancer mortality by 2030. Why is PDAC so difficult to treat and what strategies are being developed?
Many of the exosomes generated within the tumour microenvironment (TME) are not actually produced by cancer cells. Rather, they are produced by cancer-associated stromal cells and infiltrating immune cells. The role of exosomes generated by immune cells within the TME and their potential for therapeutic use is the focus of many research teams.
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?
