We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Endogenous Mesenchymal Stromal Cells in Bone Marrow Are Required to Preserve Muscle Function in mdx Mice.
- Authors
Fujita, Ryo; Nimura, Keisuke; Kaneda, Yasufumi; Tamai, Katsuto; Aikawa, Eriko; Kikuchi, Yasushi; Ishino, Saki
- Abstract
The physiological role of 'endogenous' bone marrow (BM) mesenchymal stromal cells (MSCs) in tissue regeneration is poorly understood. Here, we show the significant contribution of unique endogenous BM-MSC populations to muscle regeneration in Duchenne muscular dystrophy (DMD) mice (mdx). Transplantation of BM cells (BMCs) from 10-week-old mdx into 3-4-week-old mdx mice increased inflammation and fibrosis and reduced muscle function compared with mdx mice that received BMCs from 10-week-old wild-type mice, suggesting that the alteration of BMC populations in mdx mice affects the progression of muscle pathology. Two distinct MSC populations in BM, that is, hematopoietic lineage (Lin)−/ckit−/CD106+/CD44+ and Lin−/ckit−/CD106+/CD44− cells, were significantly reduced in 10-week-old mdx mice in disease progression. The results of a whole-transcriptome analysis indicated that these two MSC populations have distinct gene expression profiles, indicating that the Lin−/ckit−/CD106+/CD44+ and Lin−/ckit−/CD106+/CD44− MSC populations are proliferative- and dormant-state populations in BM, respectively. BM-derived Lin−/CD106+/CD44+ MSCs abundantly migrated to damaged muscles and highly expressed tumor necrosis factor-alpha-stimulated gene/protein-6 (TSG-6), an anti-inflammatory protein, in damaged muscles. We also demonstrated that TSG-6 stimulated myoblast proliferation. The injection of Lin−/ckit−/CD106+/CD44+ MSCs into the muscle of mdx mice successfully ameliorated muscle dysfunction by decreasing inflammation and enhancing muscle regeneration through TSG-6-mediated activities. Thus, we propose a novel function of the unique endogenous BM-MSC population, which countered muscle pathology progression in a DMD model. S tem C ells 2015;33:962-975
- Subjects
MESENCHYMAL stem cells; CIRCULATING anticoagulants; BONE marrow; MUSCLE tone; MICE; TISSUE engineering; DUCHENNE muscular dystrophy
- Publication
Stem Cells, 2015, Vol 33, Issue 3, p962
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.1900