Fracture Healing Effects of Locally-Administered Adipose Tissue-Derived Cells
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: Although the applications of adipose tissue-derived cells (ADCs) in regenerativemedicine have been investigated, the role of ADCs in fracture healing remains unclear. In this study, we examined the fracture-healing effects and survival of transplanted ADCs using micro-computed tomography (CT) and bioluminescenceimaging (BLI). Materials and Methods: Luciferase-expressing ADCs were suspended in solubilized basement membrane preparation (SBMP) and xenografted on defects in the right femur of nude mice (n=5). SBMP alone was grafted on a defectin the contralateral femur. Serial in vivo micro-CT and BLI were performed for 20 days. Ex vivo BLI images of both femurs were obtained. Differences in the Hounsfieldunit (HU), HUratio, and luciferase activities were compared using Wilcoxon signed-rank tests and non-parametric longitudinal analyses (p<0.05). Results: In vivo BLI revealed a signal drop on day 2, reconstitution on day 5, and continuous decrement thereafter. Ex vivo BLI revealed residual activity in the ADC-implanted and adjacent areas. No activity was detected in the contralateral femur. The overall increment rate of normalized HUs was higher for ADC-treated femurs than for SBMP-treated femurs. Cell migration to distant injury sites was not detected. Conclusion:Enhanced bone density in the implant area suggests that ADCs have fracture-healing effects.
Abstract
Purpose: Although the applications of adipose tissue-derived cells (ADCs) in regenerativemedicine have been investigated, the role of ADCs in fracture healing remains unclear. In this study, we examined the fracture-healing effects and survival of transplanted ADCs using micro-computed tomography (CT) and bioluminescenceimaging (BLI). Materials and Methods: Luciferase-expressing ADCs were suspended in solubilized basement membrane preparation (SBMP) and xenografted on defects in the right femur of nude mice (n=5). SBMP alone was grafted on a defectin the contralateral femur. Serial in vivo micro-CT and BLI were performed for 20 days. Ex vivo BLI images of both femurs were obtained. Differences in the Hounsfieldunit (HU), HUratio, and luciferase activities were compared using Wilcoxon signed-rank tests and non-parametric longitudinal analyses (p<0.05). Results: In vivo BLI revealed a signal drop on day 2, reconstitution on day 5, and continuous decrement thereafter. Ex vivo BLI revealed residual activity in the ADC-implanted and adjacent areas. No activity was detected in the contralateral femur. The overall increment rate of normalized HUs was higher for ADC-treated femurs than for SBMP-treated femurs. Cell migration to distant injury sites was not detected. Conclusion:Enhanced bone density in the implant area suggests that ADCs have fracture-healing effects.
참고문헌 (20)
- Brighton CT, "Tibial nonunion treated with direct current, capacitive coupling, or bone graft", Clin Orthop Relat Res, pp.223~234 (1995)
- Giannoudis P, "Can we accelerate fracture healing? A critical analysis of the literature", Injury, 38, pp.S81~S89 (2007)
- Tsiridis E, "Molecular aspects of fracture healing: which are the important molecules?", Injury, 38(Suppl 1), pp.S11~S25 (2007)
- Bielby R, "The role of mesenchymal stem cells in maintenance and repair of bone", Injury, 38(Suppl 1), pp.S26~S32 (2007)
- Knight MN, "Mesenchymal Stem Cells in Bone Regeneration", Adv Wound Care (New Rochelle), 2, pp.306~316 (2013)
- De Bari C, "Multipotent mesenchymal stem cells from adult human synovial membrane", Arthritis Rheum, 44, pp.1928~1942 (2001)
- Zuk PA, "Human adipose tissue is a source of multipotent stem cells", Mol Biol Cell, 13, pp.4279~4295 (2002)
- Kern S, "Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue", Stem Cells, 24, pp.1294~1301 (2006)
- Shoji T, "Local transplantation of human multipotent adipose-derived stem cells accelerates fracture healing via enhanced osteogenesis and angiogenesis", Lab Invest, 90, pp.637~649 (2010)
- Peterson B, "Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue", Tissue Eng, 11, pp.120~129 (2005)
- De Ugarte DA, "Comparison of multi-lineage cells from human adipose tissue and bone marrow", Cells Tissues Organs, 174, pp.101~109 (2003)
- Bruder SP, "Mesenchymal stem cells in osteobiology and applied bone regeneration", Clin Orthop Relat Res, 355(Suppl), pp.S247~S256 (1998)
- Cowan CM, "Adipose-derived adult stromal cells heal critical-size mouse calvarial defects", Nat Biotechnol, 22, pp.560~567 (2004)
- Lee SW, "Stem cell-mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury", J Orthop Res, 27, pp.295~302 (2009)
- Li H, "Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2", Biochem Biophys Res Commun, 356, pp.836~842 (2007)
- Bigham-Sadegh A, "Basic concepts regarding fracture healing and the current options and future directions in managing bone fractures", Int Wound J (2014)
- Schubert T, "Critical size bone defect reconstruction by an autologous 3D osteogenic-like tissue derived from differentiated adipose MSCs", Biomaterials, 34, pp.4428~4438 (2013)
- Schubert T, "The enhanced performance of bone allografts using osteogenic-differentiated adipose-derived mesenchymal stem cells", Biomaterials, 32, pp.8880~8891 (2011)
- Bruder SP, "Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells", J Orthop Res, 16, pp.155~162 (1998)
- Lyons FG, "The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs", Biomaterials, 31, pp.9232~9243 (2010)