SUMMARY
Advancements in healthcare have extended human lifespan but also increased age-related diseases such as cancer and degenerative conditions. While managing many ailments has improved, age-related illnesses remain significant challenges. RNA technology and stem cell research offer promising solutions.
The expertise of Abba C. Zubair, M.D., Ph.D., lies in transfusion medicine and stem cell therapy, focusing on regenerative medicine and immunotherapy applications that involve mesenchymal stem/stromal cells (MSC) and hematopoietic stem cells (HSC), immune cells, and extracellular vesicles (EV). Over 20 years, Dr. Zubair has led the Stem Cell Therapy Laboratory on Mayo Clinic's Florida campus, developing safe, clinical-grade cell therapy products. His research aims to harness stem cells to treat degenerative diseases and engineered immune cells to enhance therapeutic outcomes and meet regulatory standards.
Focus areas
- MSC and EV characterization and clinical-grade manufacturing. Dr. Zubair's research focuses on MSCs and EVs, as well as discovered MSC-induced neuron recovery and anti-inflammatory mechanisms. This research demonstrates MSC's neuroprotective effects and reduced apoptosis in neuron cultures. Key roles were identified for IL-6 and VEGF signaling in MSC's actions. Dr. Zubair's lab pioneered a cost-effective, automated bioreactor method for MSC and EV clinical-grade manufacturing, including an innovative messenger RNA-based technique to enhance MSCs by overexpressing transgenes such as IL-6, IL-10 and VEGF.
- Cell therapy for regenerative applications. As a cell therapist, Dr. Zubair is passionate about translating basic cell therapy research to patient care. Dr. Zubair's lab was the first to show that an external ventricular drain that is used clinically to relieve intracranial pressure and deliver medications following intracerebral hemorrhage (ICH) can be used to deliver MSCs as a means of therapy in an ICH model. Dr. Zubair's team further showed eNOS-engineered MSCs can reduce inflammation in experimental immune models. Dr. Zubair was the principal investigator and investigational new drug sponsor for two phase 1 trials that successfully evaluated the safety and feasibility of using MSC to treat patients with transplant-related bronchiolitis obliterans and ICH.
- Harnessing the uniqueness of the space environment to further understand stem cell biology and its application to the treatment of human diseases. Growing stem cells on Earth is very challenging and is limited to a few population doublings. The standard 2D culture environment is an unnatural condition for cell growth. Therefore, culturing stem cells aboard the International Space Station (ISS) under a microgravity environment may provide a more natural 3D environment for stem cell expansion and organ development. For the first time, Dr. Zubair and his team showed that MSCs grown in space under microgravity conditions were more immunosuppressive, compared to ground control. The team also showed it is feasible and potentially safe to grow MSCs aboard the ISS for potential future clinical applications. Because of this body of work, Dr. Zubair received an Exceptional Scientific Achievement Medal from NASA.
- HSC characteristics and engraftment outcomes. Dr. Zubair's early clinical career focused on HSC transplants, studying HSC characterization and engraftment outcomes. He participated in a pioneering study assessing mobilized peripheral blood CD34(+) cells from patients with coronary artery disease. He identified CD34+ subsets linked to short-term engraftment and showed that CD34(+) cells from poor and good mobilizers were qualitatively similar, with prior therapies affecting cell quantity but not quality. These studies were the first body of work that evaluated in-depth the correlation of bone marrow hematopoietic progenitor cell dose and engraftment outcome.
Significance to patient care
Dr. Zubair's research focuses on developing new treatments for various medical conditions using stem cells and related technologies:
- MSCs and EVs. Dr. Zubair's team studies MSCs and EVs, discovering ways MSCs help repair cell damage and reduce inflammation. They developed a cost-effective method to produce MSCs and EVs for clinical use, using a technique to enhance MSCs with beneficial genes.
- Cell therapy for regenerative medicine. Dr. Zubair's team has shown that MSCs can be used to treat brain hemorrhages and other conditions by reducing inflammation and promoting healing. They successfully tested these therapies in early clinical trials for lung disease and brain injury.
- Stem cells in space. Dr. Zubair explored growing stem cells in the microgravity of space, finding that they grow better and are more effective at suppressing immune responses, compared to Earth-grown cells. This research earned him the Exceptional Scientific Achievement Medal from NASA for scientific achievement.
- HSCs. Early in his career, Dr. Zubair studied blood-forming stem cells used in transplants. He identified specific cell types that affect short-term recovery and demonstrated that the quality of these cells remains high, regardless of previous treatments. This work improved the understanding of stem cell transplants.
Overall, Dr. Zubair's work aims to create new, effective treatments for conditions that currently have limited options, thereby improving patient care and outcomes.