A Publication of WTVP

Craig Cady, PhD, is an associate professor and director of the Bohlander Stem Cell Research Laboratory in the Biology Department at Bradley University. Working with his team of undergraduate and graduate students and various other collaborators, he is focused on cutting-edge research to find cures for major diseases—transforming stem cells into functional neurons, heart cells and cancer-fighting cells. iBi checked in with Dr. Cady to discuss his team’s current research, advances in the field, milestones and obstacles, and the state of basic science research.

Please list and describe your primary research projects at the Bohlander Stem Cell Research Laboratory.
Enhancing migration of genetically engineered stem cells toward ovarian cancer cells. Our research with genetically engineered stem cells showed they migrate towards ovarian cancer and then produce a protein that changes a “prodrug” into a cancer-killing drug. This cell-based system has the potential to treat advanced ovarian cancer. We recently developed a chemical mix that rapidly increases the aggressiveness of this stem cell migration, making the system more efficient. This system has been tested in our laboratory; however, we want to test the efficiency of this system using an animal model of ovarian cancer.

Cancer stem cells. CSCs are present in nearly all tumors. These unique cancer cells are resistant to chemotherapy and radiation. In fact, treatments for cancer can activate CSCs, causing recurrence of disease—a deadly aspect of cancer. Many researchers feel we have been targeting the wrong cancer cell type and should be looking more closely at inhibiting CSCs to block recurrence of cancer. Our new project tests if our stem cell base system will cause stem cells to migrate toward and destroy CSCs. We recently acquired our first ovarian CSC line. It is our hope to inhibit CSCs and limit the recurrence of ovarian cancer.

Producing a nanofiber material for the replacement of damaged tissue. A new project involves producing a biocompatible nanofiber material embedded with factors that help stem cells become cells of the nervous system. These factors are slowly released from the nanomaterial onto stem cells, which causes them to become new cells of the nervous system. Our objective is to provide a possible substrate to replace damaged nervous tissue.

Using nanofiber materials for the replacement of skin following traumatic injury. In collaboration with the SIU School of Medicine Department of Surgery, we’re investigating how to replace skin following traumatic injury using nanofiber materials and stem cells. Our collaborators in the surgery department have developed an animal model of traumatic injury to test our new materials in replacing skin.

Hydrogel nanofiber materials for the production and packaging of heart cells and dopamine-secreting cells from iPS stem cells. Our success in producing beating human heart cells and dopamine-secreting cells from stem cells has led to a new project. Our goal is to package iPS stem cells into a hydrogel material, then induce them to become heart cells or dopamine-producing cells. This complex would be transplanted at the site of injury or damage; the packaged cells would be protected from further disease while remaining at the site of injury.

Using 3D culture to improve the conversion of stem cells into neurons. In the body, stem cells live in a tight microenvironment termed “the stem cell niche.” We’re attempting to mimic this microenvironment in the laboratory using a 3D culture system, versus the usual flat culture dish. Our goal is to provide a more natural microenvironment to improve our efficiency in changing stem cells into dopamine-producing, neuron-like cells. These cells could be used to treat Parkinson’s disease, for example.

What are some significant milestones recently accomplished in your research?
We’re the first to successfully generate parathyroid hormone-producing cells from stem cells. This was exciting and has the potential to effectively treat hypoparathyroidism. Another milestone was the acquisition of electrospinning instruments that produce a variety of nanofiber materials. Previously, we had to rely on off-site laboratories to produce these materials. This has accelerated our nanofiber/stem cell research, allowing us to produce custom materials targeted at replacing heart cells for our research on heart failure and dopamine-producing cells for our Parkinson’s disease research.

What advances in stem cell research have taken place in recent years?
The discovery of induced pluripotent (iPS) stem cells for the replacement of damaged or diseased tissue was a major change in regenerative medicine. iPS stem cells can be produced from individual patients and make any cell type in the body for implantation without tissue rejection. This field has accelerated and is now in clinical trials. Our laboratory was fortunate to acquire an iPS stem cell line from Dr. James Thomson’s laboratory at the WiCell Institute, and we’re currently producing functional human heart cells and pacemaker cells, among other cell types.

Another major breakthrough has been the discovery of “exosomes”—small vesicles released by stem cells that can change how other cells function. This discovery explained how stem cells improve damaged tissue without directly contacting the tissue. Exosomes contain many factors that can genetically alter the function of other cells, and it’s quickly becoming a major field of interest. We knew factors produced by stem cells could improve brain cell growth in our laboratory, but the discovery of exosomes explains why this is effective. Our laboratory has started isolating exosomes and looking at the potential to utilize them for neuroprotection from neurological diseases.

What is cell-based therapy, and how is it being used to treat diseases today?
Cell-based therapy is the use of living cells as therapeutic agents. A recent success was regenerating tissue in the retina to improve vision for patients suffering from macular degeneration. Other examples include producing bone from a patient’s own bone marrow stem cells for congenital defects to replace missing tissues, and a recent immunotherapy for cancer termed CAR-T immunotherapy (Chimeric Antigen Receptor Therapy), where the patient’s own T cells are reprogrammed to help identify and destroy cancer.

What diseases or ailments show the most promise for this research?
Macular degeneration is one of the most promising clinical applications of embryonic stem cells. In addition, diabetes—with the production of insulin-producing cells—is very promising and will be one of the most hopeful clinical applications of stem cells.

How do you acquire a line of stem cells?
Due to the limited source of umbilical cord stem cells in the Peoria area, we have had to find commercial sources and were fortunate to locate some outside of Peoria. We have also expanded our iPS stem cell line to have a large-enough bank of cells to be self-reliant. Expecting families in Peoria who are considering donating umbilical stem cells may do so by contacting me at (309) 677-3012.

What does the current landscape for basic science research in the U.S. look like?
Funding from federal institutions such as the NIH and NSF remains limited and has not kept up with the need for new research and technology. For investigators at smaller institutions, like myself, federal funding is even more limited. This has inhibited progress. I want to thank the people of Peoria—particularly the Don Bohlander Parkinson’s Foundation and the Cox Family Foundation—for supporting our research, allowing us to compete in this field on a global scale.

Availability for research funding in the U.S. is no longer competitive with other countries. We’re losing a significant number of research scientists to countries willing to support advanced research, particularly in the field of regenerative medicine. As an American scientist, it’s disheartening to see our funding priorities leave research behind, allowing other countries to advance at a faster rate.

Have any of your former students remained in this field?
Although Bradley University is a small institution, my students have gone on to make significant contributions to this field. I have students at more than 10 major academic institutions seeking graduate degrees, including Duke, Northwestern and Washington University. They are contributing to stem cell research in Parkinson’s disease, cardiac disease and diabetes.

What is the biggest obstacle to overcome in your current work?
The extent and rate at which we are able to perform stem cell research is directly related to the resources that are provided to our team. Instrumentation, for example, is particularly expensive and remains our primary constraint. If we could raise more funding, we would have more instrumentation and be able to expand our work. Because of our collaboration with Southern Illinois School of Medicine at Springfield, we have had access to instrumentation at a minimal cost. However, it would be useful to have these instruments available here in Peoria.

What are you most hopeful about?
The field of regenerative medicine is the new horizon in medicine. We will soon see even more technology from this field translate into medical applications. The number of clinical trials related to regenerative medicine is increasing every year. This was evident this year at the World Stem Cell Summit, and I remain excited about continuing to contribute to this important field.

Anything else you wish to add?
I would like to thank Bradley University, the Peoria community, and all those who have so generously donated to our stem cell research laboratory and the field in general. Our commitment is derived from our passion for research and the desire to find cures to diseases that affect the lives of so many. iBi