Researchers at the biomedical research center Helmholtz Munich in Germany have developed a label-free imaging method that can track whether or not a multiple myeloma treatment is working in single cells. This can help physicians make personalized therapy adjustments based on the cancer’s response to treatment.
Multiple myeloma is the third most common blood cancer, with incidences on the rise. It affects a type of white blood cell, called plasma cells, in the bone marrow.
The study, published in Nature Biomedical Engineering and titled “Label-Free Protein-Structure-Sensitive Live-Cell Microscopy for Patient-Specific Assessment of Myeloma Therapy,” introduces the method called MiROM, which uses infrared light to cause molecular vibrations within proteins, resulting in the emission of ultrasound waves. MiROM captures these ultrasound waves in real-time and, based on these, can find and analyze structural changes in proteins within individual cells.
MiROM can detect structures associated with protein misfolding, called intermolecular beta-sheets, as well as programmed cell death—apoptosis—which is a clear indicator of whether or not a cancer treatment is working or whether the cancer is developing a resistance to the treatment.
In the study, the researchers specifically looked at the effectiveness of multiple myeloma treatments, using intermolecular beta-sheets as hallmarks of misfolded protein formation and consequent cell death.
To confirm that MiROM could indeed detect intermolecular beta-sheets, the team grew human multiple myeloma cells in culture and treated them with the chemotherapy drug doxorubicin, which results in cell cycle arrest. They also imaged untreated multiple myeloma cells for comparison.
Currently, it can be challenging to monitor the effectiveness of a multiple myeloma therapy because traditional methods often require large cell samples, are time-intensive, and complex to prepare. Moreover, they only offer information on the entirety of the tumor, rather than single cells.
“Since MiROM can analyze individual cells in real time without the need for elaborate sample preparation, it offers fast insights into how treatments may impact protein structures at a cellular level,” explained Francesca Gasparin, PhD, a researcher at the Institute of Biological and Medical Imaging at Helmholtz Munich, chair of biological imaging at the Technical University of Munich, and the first author of the study.
The clinical application of MiROM extends beyond evaluating the effectiveness of multiple myeloma treatments. Patients of other diseases linked to protein misfolding, such as Alzheimer’s or Parkinson’s disease, could benefit too.
“We envision the use of MiROM in drug screening, diagnostic tests, and home-based patient monitoring,” said Vasilis Ntziachristos, PhD, head of the Bioengineering Center and the Institute of Biological and Medical Imaging at Helmholtz Munich, and senior investigator in the study.
The research team now wants to test their method in larger patient cohorts to gain further clinical validation and bring the technology into routine medical practice in the future.
