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At the Mayo Clinic, Dr. Guifang Zhao is leading a new generation of regenerative medicine therapies that combine the precision of gene-based design with the body’s natural healing mechanisms. Her research focuses on developing cell-free, exosome-mediated mRNA delivery systems to restore damaged tissues and organs, offering new hope for patients with chronic wounds, intervertebral disc degeneration, and osteoarthritis.
“Traditional stem cell therapies have shown promise but face challenges in safety, stability, and manufacturing,” explains Dr. Zhao. “By integrating mRNA and exosome technologies, we can activate the body’s repair mechanisms without using live cells; this represents a major step forward in regenerative medicine.”
The research of Dr. Zhao is focused on stem cell-derived exosomes, which are tiny vesicles that serve as natural communication between the cells. Her team alters the exosomes so that the therapeutic mRNA is sent along with them, thus allowing the specified moderation of the cellular repair and immune responses. This remarkable development could be the answer to the long-term treatment of chronic degenerative conditions, which are now lacking effective solutions.
Her studies have demonstrated how exosome-based signaling promotes angiogenesis, collagen remodeling, and accelerated wound closure. In one of her landmark papers, published in Stem Cell Research & Therapy (2015), Dr. Zhao was among the early researchers to identify how mesenchymal stem cell-derived exosomes stimulate skin regeneration. Later, her 2022 study in Stem Cell Research & Therapy expanded this discovery by demonstrating enhanced wound healing through hypoxia-preconditioned exosomes. Her most recent publication in the Journal of Controlled Release (2024) reported a novel hydrogel-exosome hybrid platform for sustained mRNA delivery to chronic wounds, paving the way for minimally invasive regenerative therapies.
Dr. Zhao during her twelve-year long career in stem cell and regenerative medicine has been the one to change the paradigm from the traditional cell therapy to the cell-free, exosome-mediated gene regulation. Such an approach not only enhances safety and reproducibility but also meets the U.S. healthcare system's demand for scalable biologics.
At the Mayo Clinic, Dr. Zhao has also expanded her mRNA-based gene therapy for osteoarthritis and intervertebral disc degeneration, which are two of the main factors causing chronic disability in the world, thereby leading to her development of the very mRNA candidates necessary for clinical translation. Through the combination of exosome engineering and mRNA design, she envisions her research will repair the cartilage and disc tissues via self-activated molecular pathways, thereby restoring structure and function.
Dr. Zhao’s research contributes to strengthening the United States’ leadership in regenerative medicine and biotechnology. Chronic degenerative and musculoskeletal diseases affect more than 50 million Americans, leading to escalating healthcare costs and reduced quality of life. Her exosome–mRNA platform offers a scalable, biocompatible, and cost-effective therapeutic model that aligns with the U.S. Department of Health’s strategic goals for innovation-driven healthcare.
“Science is most powerful when it serves patients,” says Dr. Zhao. “My mission is to transform laboratory discoveries into real therapies that help the body heal itself.”
Dr. Zhao envisions establishing a cross-disciplinary research program in the United States that integrates stem cell biology, exosome engineering, and gene therapy into a unified translational pipeline. With over 30 peer-reviewed publications and service as a reviewer for nearly 20 international journals, she continues to advance the scientific foundation for next-generation regenerative therapies.
