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 delta-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-kappaB 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.
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 delta-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-kappaB 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.
Authors: T X Fan; H Hisha; T N Jin; C Z Yu; Z X Lian; S B Guo; Y Z Cui; B Feng; G X Yang; Q Li; S Ikehara Journal: Stem Cells Date: 2001 Impact factor: 6.277
Authors: Tsutomu Ryoke; Yusu Gu; Yasuhiro Ikeda; Maryann E Martone; Sam S Oh; Eun-Seok Jeon; Kirk U Knowlton; John Ross Journal: Basic Res Cardiol Date: 2002-01 Impact factor: 17.165
Authors: K Yuasa; M Sakamoto; Y Miyagoe-Suzuki; A Tanouchi; H Yamamoto; J Li; J S Chamberlain; X Xiao; S Takeda Journal: Gene Ther Date: 2002-12 Impact factor: 5.250
Authors: Georg Wieczorek; Christine Steinhoff; Ralph Schulz; Marina Scheller; Martin Vingron; H-Hilger Ropers; Ulrike A Nuber Journal: Cell Tissue Res Date: 2003-01-31 Impact factor: 5.249
Authors: Rafael Moreno; Itziar Martínez-González; Marta Rosal; Marga Nadal; Jordi Petriz; Eduard Gratacós; Josep M Aran Journal: Stem Cells Dev Date: 2011-06-01 Impact factor: 3.272