Acceleration of Skeletal Muscle Regeneration in a Rat Skeletal Muscle Injury Model by Local Injection of Human Peripheral Blood-Derived CD133-Positive Cells  

Abstract

Muscle injuries in sport activities can pose challenging problems in traumatology and sports medicine. The best treatment for muscle injury has not been clearly established except for the conservative treatment that is routinely performed. We investigated the potential of human adult CD1331 cells to contribute to skeletal muscle regeneration in an athymic rat model. We tested whether CD1331 cells locally transplanted to the skeletal muscle lacerated models could (a) induce vasculogenesis/angiogenesis, (b) differentiate into endothelial and myogenic lineages, and (c) finally promote histological and functional skeletal myogenesis. Granulocyte colony stimulating factor-mobilized peripheral blood (PB) CD1331 cells, PB mononuclear cells, or phosphate-buffered saline was locally injected after creating a muscle laceration in the tibialis anterior muscle in athymic rats. After treatment, histological and functional skeletal myogenesis was observed significantly in the CD1331 group. The injected CD1331 cells differentiated into endothelial and myogenic lineages. Using real-time polymerase chain reaction analysis, we found that the gene expressions related to microenvironment conduction for host angiogenesis, fibrosis, and myogenesis were ideally up/downregulated. Our results show that CD1331 cells have the potential to enhance the histological and functional recovery from skeletal muscle injury rather via indirect contribution to environment conduction for muscular regeneration. It would be relatively easy to purify this cell fraction from PB, which could be a feasible and attractive autologous candidate for skeletal muscle injuries in a clinical setting. These advantages could accelerate the progression of cell-based therapies for skeletal muscle injuries from laboratory to clinical implementation. STEM CELLS 2009;27:949-960 Disclosure of potential conflicts of interest is found at the end of this article.

Magnetic Targeting of Human Peripheral Blood CD133+Cells for Skeletal Muscle Regeneration

“…11 Briefly, female F344/NJcl-rnu/rnu athymic nude rats (9 weeks old, n = 39) were anesthetized using intraperitoneal pentobarbital sodium (50 mg/kg). The muscle belly of tibialis anterior muscle was lacerated transversely using a scalpel.…”

“…[2][3][4][5][6][7][8][9][10] Recently, we showed that transplantation of human peripheral blood CD133-expressing cells (CD133 + cells) inhibits fibrosis and improves muscle regeneration after skeletal muscle laceration. 11 Human blood CD133 + cells are wellsuited for clinical applications, because collecting these cells is safe, with limited ethical problems. However, obtaining a sufficient number of cells is the most important factor limiting clinical application, as the proportion of CD133 + cells to mononuclear cells (MNCs) in human blood is small.…”

Pluripotent Stem Cells and Their Dynamic Niche

“…MSCs with similar properties to bone marrow-derived MSC have been isolated from trabecular bone [162], periosteum [163], synovial membrane [164], skeletal muscle [165], skin [166], pericytes [167], peripheral blood [168] and umbilical cord [169,170]. Due to their low number upon isolation, adult stem cells require in vitro expansion and modification before being employed therapeutically [63].…”

Mesenchymal Stem Cells Improve Muscle Function Following Single Stretch Injury: A Preliminary Study

“…Many benefits of MSC transplantation are attributed to a strong paracrine capacity, including increased angiogenesis, decreased fibrosis, immunomodulation, and secretion of survival and stem cell recruitment factors [17]. Gene expression in the injury microenvironment also appears optimally altered by the presence of stem cells to promote angiogenesis and myogenesis and limit fibrosis [18]. Taking advantage of the pro-regenerative properties of stem cells to regulate endogenous tissue regeneration via this mechanism is promising for clinical intervention.…”