Use of mesoangioblasts, and mesenchymal stem cells to treat muscular dystrophy in animals
My research interests include 1) utilizing vessel-derived stem cells, known as mesoangioblasts, and mesenchymal stem cells to treat muscle damage in animal models for muscular dystrophy, 2) studying the in vitro differentiation potential of these cells in anticipation of their use to repair damage to other tissue types, and 3) the isolation and characterization of, and development of culture conditions for, mesoangioblasts from human tissues. In a recent study we have demonstrated that murine aorta-derived mesoangioblasts can be used to treat severe muscle damage in an animal model for Duchenne muscular dystrophy. Injection of undifferentiated mesoangioblasts into damaged skeletal muscle results in the formation of healthy muscle fibers as well as other mature cell types that are damaged during the progression of muscle disease, including smooth muscle cells in arteries, and glial cells in peripheral nerve bundles. These data suggest that aorta-derived mesoangioblasts may be used to fully repair damage that occurs in Duchenne muscular dystrophy, encompassing myofiber damage, denervation, and the rupture of vessels within skeletal muscle. To fully establish the clinical relevance of these findings it is necessary to determine whether an analogous population of cells resides in human vessels, and if different vessels contain stem cells with variable markers and differentiation characteristics. An unexpected finding during this recent study was the apparent neural potential of mesoangioblasts derived from the murine aorta. Further in vitro characterization of this potential is currently in progress, and cells isolated from human vessels will also be tested for their ability to enter the neural lineage as well. Additional areas of research include screening human stem cells from a variety of adult tissues and umbilical cord blood, obtained through a collaborative effort with Cellular Engineering Technologies, Inc., for their potential to differentiate into muscle and nerve, and to repair damage to these tissue types in vivo.
Suzanne E. Berry, Jianming Liu, Eric J. Chaney, and Stephen J. Kaufman. Multipotential Mesoangiobast Stem Cell Therapy in the mdx/utrn-/- Mouse Model for Duchenne Muscular Dystrophy. Regenerative Medicine 2: 275-288, 2007.
Suzanne E. Berry, Melissa Hentges, and Stephen J. Kaufman. In vitro and in vivo Neural Potential of Aorta-derived Mesoangioblasts. Manuscript in Preparation.
Suzanne E. Berry, Tamellote Loh, Tao Yan, and Timothy J. Kinsella. Role of MutSalpha in the Recognition of Iododeoxyuridine in DNA. Cancer Res 63:5490-5495, 2003.
Tao Yan, Suzanne E. Berry, Anand B. Desai, and Timothy J. Kinsella. DNA Mismatch Repair (MMR) Mediates 6-Thioguqnine Genotoxicity by Introducing Single-strand Breaks to Signal a G(2)-M Arrest in MMR-proficient RKO Cells. Clin Cancer Res 9:2327-2334, 2003.
Tao Yan, Jane E. Schupp, Hwa-Shin Hwang, Mark W. Wagner, Suzanne E. Berry, Sue Strickfaden, Martina L. Veigl, David Sedwick, David A. Boothman, and Timothy J. Kinsella. Loss of DNA Mismatch Repair Imparts Defective cdc2 Signaling and G(2)-M Arrest Responses Without Altering Survival After Ionizing Radiation. Cancer Research 61:8290-8297, 2001.
Suzanne E. Berry and Timothy J. Kinsella. Targeting DNA Mismatch Repair for Radiosensitization. Seminars in Radiation Oncology 11:300-315, 2001.
Suzanne E. Berry, Thomas W. Davis, Jane E. Schupp, Hwa-Shin Hwang, Niels de Wind, and Timothy J. Kinsella. Selective Radiosensitization of Drug-Resistant MutS Homologue-2 (MSH2) Mismatch Repair-deficient Cells by Halogenated Thymidine (dThd) Analogues: Msh2 Mediated dThd Analogue DNA Levels and the Differential Cytotoxicity and Cell Cycle Effects of the dThd Analogues and 6-Thioguanine. Cancer Research 60:5773-5780, 2000.
Timothy J. Kinsella, Jane E. Schupp, Thomas W. Davis, Suzanne E. Berry, Hwa-Shin Hwang, Kathy Warren, Frank Balis, John Barnett, and Howard Sands. Pre-clinical Study of the Systemic Toxicity and Pharmacokinetics of 5-Iodo-2-Deoxypyrimidinone-2'-Deoxyribose (IPdR) as a Radiosensitizing Prodrug in Two Non-rodent Animal Species: Implications for Phase I Study Design. Clinical Cancer Research 6:3670-3679, 2000.
Suzanne E. Berry, Christopher A. Garces, Hwa-Shin Hwang, Keith Kunugi, Mark Meyers, Thomas W. Davis, David A. Boothman, and Timothy J. Kinsella. The Mismatch Repair Protein, hMLH1, Mediates 5-substituted Halogenated Thymidine Analog Cytotoxicity, DNA Incorporation, and Radiosensitization in Human Colon Cancer Cells. Cancer Research 59:1840-1845, 1999.