Post by David Feder on May 7, 2009 20:18:52 GMT -5
Muscular Dystrophy Therapy by Nonautologous
Mesenchymal Stem Cells: Muscle Regeneration
Without Immunosuppression and Inflammation
Arsalan Shabbir, David Zisa, Merced Leiker, Curtis Johnston, Huey Lin, and Techung Lee -USA
Background. The use of nonautologous stem cells isolated from healthy donors for stem-cell therapy is an attractive
approach, because the stem cells can be culture expanded in advance, thoroughly tested, and formulated into off-the-shelf
medicine. However, human leukocyte antigen compatibility and related immunosuppressive protocols can compromise
therapeutic efficacy and cause unwanted side effects.
Methods. Mesenchymal stem cells (MSCs) have been postulated to possess unique immune regulatory function. We
explored the immunomodulatory property of human and porcine MSCs for the treatment of -sarcoglycan-deficient
dystrophic hamster muscle without immunosuppression. Circulating and tissue markers of inflammation were analyzed.
Muscle regeneration and stem-cell fate were characterized.
Results. Total white blood cell counts and leukocyte-distribution profiles were similar among the saline- and MSC-injected
dystrophic hamsters 1 month posttreatment. Circulating levels of immunoglobulin A, vascular cell adhesion molecule-1,
myeloperoxidase, and major cytokines involved in inflammatory response were not elevated by MSCs, nor were expression
of the leukocyte common antigen CD45 and the cytokine transcriptional activator NF-B in the injected muscle. Treated
muscles exhibited increased cell-cycle activity and attenuated oxidative stress. Injected MSCs were found to be trapped in the
musculature, contribute to both preexisting and new muscle fibers, and mediates capillary formation.
Conclusions. Intramuscular injection of nonautologous MSCs can be safely used for the treatment of dystrophic
muscle in immunocompetent hosts without inflaming the host immune system.
Mesenchymal Stem Cells: Muscle Regeneration
Without Immunosuppression and Inflammation
Arsalan Shabbir, David Zisa, Merced Leiker, Curtis Johnston, Huey Lin, and Techung Lee -USA
Background. The use of nonautologous stem cells isolated from healthy donors for stem-cell therapy is an attractive
approach, because the stem cells can be culture expanded in advance, thoroughly tested, and formulated into off-the-shelf
medicine. However, human leukocyte antigen compatibility and related immunosuppressive protocols can compromise
therapeutic efficacy and cause unwanted side effects.
Methods. Mesenchymal stem cells (MSCs) have been postulated to possess unique immune regulatory function. We
explored the immunomodulatory property of human and porcine MSCs for the treatment of -sarcoglycan-deficient
dystrophic hamster muscle without immunosuppression. Circulating and tissue markers of inflammation were analyzed.
Muscle regeneration and stem-cell fate were characterized.
Results. Total white blood cell counts and leukocyte-distribution profiles were similar among the saline- and MSC-injected
dystrophic hamsters 1 month posttreatment. Circulating levels of immunoglobulin A, vascular cell adhesion molecule-1,
myeloperoxidase, and major cytokines involved in inflammatory response were not elevated by MSCs, nor were expression
of the leukocyte common antigen CD45 and the cytokine transcriptional activator NF-B in the injected muscle. Treated
muscles exhibited increased cell-cycle activity and attenuated oxidative stress. Injected MSCs were found to be trapped in the
musculature, contribute to both preexisting and new muscle fibers, and mediates capillary formation.
Conclusions. Intramuscular injection of nonautologous MSCs can be safely used for the treatment of dystrophic
muscle in immunocompetent hosts without inflaming the host immune system.