One of the earliest uses of stem cells in the clinic was for the treatment of people with blood cancers such as leukemia. These cancers occur when white blood cells, which are normally responsible for fighting infections, begin to reproduce uncontrollably and take over other organs. Chemotherapy can often kill most of these cancerous cells, but unfortunately, a very strong dose must be used – so strong in fact that the chemotherapy also kills most of the patient’s normal white blood cells, leaving them vulnerable to potentially deadly infections.
The only way to keep the patient alive after this strong chemotherapy is to give them a bone marrow stem cell transplant. The stem cell transplant fights off infections and attacks any of the patient's surviving white blood, including the cancerous leukemia cells.
This chemotherapy / bone marrow stem cell transplant combination has saved the lives of thousands of people, but it is not perfect. Sometimes the transplant is “rejected” by the patient, or sometimes there are toxic side effects. Scientists at the Sprott Centre for Stem Cell Research believe they can dramatically improve the success of this procedure, but they need a new piece of equipment called an Orbitrap Mass Spectrometer to do it.
Dr. Rudnicki further shared with me that his team is anxious to use the new mass spectrometer for diabetes research and that they wish to identify the cell surface proteins bound by Periostin. This is a critical next step towards understanding the mode of Periostin function in inducing pancreas regeneration.
The background to this research experiment is as follows: We identified a novel splice isoform of Periostin to be highly induced in the regenerating pancreas following partial pancreatectomy (surgical removal of 70% of the pancreas). Periostin is a secreted protein that induces cell motility and activation/proliferation of stem cells. Notably, we found that mice lacking Periostin were entirely defective in pancreas regeneration following partial pancreatectomy. Direct injection of Periostin protein into the pancreas initially induces the proliferation of stellate cells, which accumulate to form an extensive mesenchymal stroma. Subsequently, tubular complexes develop followed by expression of Ngn-3 and Pdx-1 in islet progenitors and the formation of insulin expressing islets.
Importantly, Periostin injection induced pancreatic regeneration, islet neogenesis and restoration of normal blood glucose levels in streptozotocin (STZ)-induced diabetic mice. Therefore, Periostin is necessary and sufficient for the induction of pancreas regeneration and represents a novel therapeutic avenue for the investigation of the treatment of Type 1 Diabetes.
Dr. Rudnicki looks forward to aggressively exploring this project and this technology further in the coming months.
Here’s how it will work:
The Orbitrap will accelerate many kinds of stem cell research and will accelerate the development of new therapies used for important conditions such as stroke, heart attack and diabetes.The Orbitrap can detect very tiny amounts of specific proteins in rare populations of cells. It is 10 times more sensitive than the version of the machine that is currently available. It would allow researchers to measure stem cell proteins and contaminating proteins in every transplant before it is given.
Not only would this help patients avoid potentially harmful transplants – it would also eventually allow us to develop a method to better purify transplants, so that they work every time instead of just some of the time. There is a strong possibility that this equipment will also improve the success of newer bone marrow stem cell transplant therapies, such as those used for patients with multiple sclerosis, Crohn’s and arthritis.
The Orbitrap will help researchers investigate a very new and powerful technique that has been developed to “reprogram” normal cells so that they turn into stem cells. This technique holds enormous promise because it could allow researchers to prepare an unlimited supply of stem cells that would be personalized for each patient. With the acquisition of the Orbitrap, Ottawa and Canada will remain at the forefront of this research.