Dr. Joanne Kurtzberg is a stem cell pioneer and has advanced the development of innovative stem cell therapies including those based on umbilical cord blood.
She is a faculty member at Duke where she conducts her clinical research. I recently interviewed Dr. Kurtzberg and below is Part 1 of 2 of the interview.
Part 2, which has fascinating insights on helping patients steer clear of non-compliant clinics, what excites Kurtzberg the most about stem cells, and her view of the future of the field can be found here.
1. How did you first get interested in stem cells as a potential basis for medical treatments? Was there a particular “aha!” kind of moment? What about key mentors for you earlier in your career?
I first became interested in stem cells when I was a fellow in Hematology/Oncology and treated a teenage boy with refractory T-cell Acute Lymphoblastic Leukemia with an experimental drug which was a nucleoside analog which induced differentiation of his leukemic cells from a T-lymphoblastoid to a mature myeloid phenotype. The conversion also induced control of the leukemic process and induced a remission. I subsequently established a cell line from this patient’s leukemic cells and began to study the mechanisms underlying ‘stemness’, stem cell differentiation and leukemogenesis. During this time, I worked in the laboratory of Dr. Michael Hershfield who was my mentor.
I also was fortunate to get to know Gertrude Elion (Trudy), who later won the Nobel Prize in Medicine with George Hitchings. I was working with a mouse model of T-cell lymphoma and Trudy gave me a vial of a compound she’d synthesized years before. The compound was active in the mouse model and I worked with Trudy and Bev Mitchell to get an investigator initiated IND to bring it into the first clinical trial. Long story short this led to the development of nelarabine which was licensed by the FDA for the treatment of T-cell Leukemia many years later.
2. What makes you particularly excited about cord blood as a tool for treating pediatric patients? How is cord blood different from other kinds of stem cells in terms of therapeutic potential? What are its strengths and weaknesses?
Cord blood is the optimal form of mobilized blood. It is comprised of mature blood cells, hematopoietic stem and progenitor cells and rare stem and progenitor cells of other lineages (pancreas, brain, muscle, endothelial cells, elements of skin, and perhaps others). I think that cord blood has enormous potential for use in the emerging field of regenerative medicine. Cord blood T cells are more immunologically tolerant of a new host as compared to adult hematopoietic cells. Cord blood can be collected from the placenta, or afterbirth, shortly after delivery of the baby without any risk to the baby or mother. Cord blood is often discarded after birth. Harvesting of cord blood, banking and subsequent therapeutic applications is taking medical waste and converting it to life-saving therapies.
3. Can cord blood cells get into the CNS and engraft in clinically meaningful levels? What’s the data like on this for humans? Given the blood brain barrier, what is the mechanism by which cord blood cells enter the human CNS?
Yes, cord blood cells cross the blood brain barrier and engraft in high levels, mostly as microglial cells, after myeloablative chemotherapy and intravenous delivery. Cells migrate through the choroid plexus to enter the brain.
4. Once cord blood cells have entered the CNS, how might the cells help patients such as the kids who have cerebral palsy (CP)? Is it a ‘cell therapy’ kind of approach in the sense that the cord blood cells actually grow into useful cells in the brain? Or do they mostly work by mobilizing endogenous stem cells in the brain? Stimulating angiogenesis? Other mechanisms? What do we know concretely about potential mechanisms of cord blood being helpful for neurological diseases?
I believe that cord blood cells help patients with brain injuries primarily through paracrine and trophic effects.
I think they decrease inflammation and stimulate endogenous neurogenesis and endothelial repair. Cord blood cells are capable of differentiating into neurons, oligodendrocytes and microglia in vitro. I think this capability is helpful to patients with leukodystrophies who undergo allogeneic stem cell transplantation with cord blood. In these cases, the donor cord blood cells engrafting in the brain also serve as a source of permanent cellular enzyme replacement therapy.
5. How are the clinical trial(s) going (e.g. http://clinicaltrials.gov/ct2/show/NCT01147653?term=NCT01147653&rank=1)?
They are ongoing. It is too early to talk about results.
6. Are there other pediatric diseases for which cord blood cells may be clinically useful besides CP? Do you envision the mechanism of therapeutic benefit being similar or distinct?
Allogeneic cord blood transplantation is used to treat children with leukemias and other hematological malignancies, bone marrow failure syndromes, inherited immunodeficiency syndromes, certain inherited metabolic diseases and hemoglobinopathies.
I believe that autologous cord blood may have a role in treating children with type I diabetes, other autoimmune diseases, and brain and cardiac injuries.
7. What exactly are the clinically important cells in cord blood, which is a heterogeneous substance, beyond hematopoietic stem cell and progenitor cells? Do you believe in the notion of pluripotent stem cells in cord blood?
Yes, see above.
8. What do you think of very small embryonic-like stem cells (VSELs)?
I don’t know what to think about VSELS. I do think there are very small numbers of ES like cells in cord blood. I’m not sure VSELS are those cells. I think the numbers are 10-20 and are not likely to be clinically useful for now.
Stay tuned for Part 2 of the interview in a few days!