Manipulating Stem Cells for Repair and Drug Delivery at Various Anatomic Sites
Summary Cellular and gene therapy for chronic drug delivery and tissue repair have been explored in a range of anatomic sites including the heart, brain, bone marrow, and skeletal muscle. Mashimo and colleagues present a new approach using modified embryonic stem (ES) cells to deliver drugs to the gastrointestinal system and to repair gastrointestinal tissue using somatic stem cells.A preliminary application of the embryonic stem cell delivery technology targets NO deficiency. NO deficiency has been implicated in a variety of GI motility disorders in humans (e.g., achalasia, diabetic gastroparesis, Hirschsprung’s disease, infantile hypertrophic pyloric stenosis), for which current pharmacological therapies lack sufficient biological half-life, diffuse rapidly, and lead to systemic side-effects. Embryonic stem cells, manipulated to express the gene for nitric oxide synthase, were implanted into the pylorus of mice knockouts (nNOS-/-, neuronal nitric oxide synthase) expressing the phenotype for NO deficiency. The injected ES cells led to increased levels of NO to relax the pylorus at clinically relevant levels. Moreover, implanted ES cells survived long-term in vivo, remained at or near the injected site, and respected local tissue architecture (i.e., no marked inflammatory reaction, no tumors observed).
The Mashimo invention portfolio also covers the use of somatic stem cells for tissue repair in the gut, which could apply to disorders including achalasia, Hirschsprung’s and IBD. Somatic stem cells were isolated from bone marrow, as well as small intestine cells and colonic epithelial cells. The different stem cell types demonstrated viability at the site of injection in the stomach, and differentiated to express functional markers of native tissue.
Commercial Applications and Markets: The chronic delivery of nitric oxide based on Mashimo’s ES cell delivery technology may have clinical application for various conditions characterized by NO deficiency. Further proof-of-concept studies have shown that chronic NO delivery using ES cells are also applicable at anatomic sites other than the stomach. This may enable applications targeting male impotence (e.g., Viagara effect), hypertension (e.g., pulmonary, hepatic and systemic), treatment of vascular and other luminal stenoses, and ischemia. Extensions of the Mashimo technology may also address the delivery of other gene products, including enzymes, signaling peptides, hormones and structural proteins.
Patent Status:
Harvard has filed for a U.S. utility patent, claiming isolation and transfection of stem cells with a functional protein, including nitric oxide synthase, as well as methods of treatment covering the implantation of such cells at various anatomic sites, including the gastrointestinal system.
Applications Gene therapy delivery system Peptide delivery system Protein delivery system For Further Information Please Contact the Director of Business Development Vivian Berlin Email: [email protected] Telephone: (617) 495-0474
Inventor(s): Mashimo, Hiroshi
Type of Offer: Licensing
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