TY - JOUR
T1 - Regeneration of Vascularized Corticocancellous Bone and Diploic Space Using Muscle-Derived Stem Cells
T2 - A Translational Biologic Alternative for Healing Critical Bone Defects
AU - Lough, Denver
AU - Swanson, Edward
AU - Sopko, Nikolai A.
AU - Madsen, Christopher
AU - Miller, Devin
AU - Wang, Howard
AU - Guo, Qiongyu
AU - Sursala, Srinivas M.
AU - Kumar, Anand R.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background: Regeneration of functional bone substrate remains a priority in reconstructive surgery especially for patients suffering from complex skeletal defects. Efforts to develop implantable osteoinductive constructs and novel osteoconductive materials remain at the forefront of industry forces and product line development. Despite advancement in clinical practice and bone biology, cancellous autograft remains the gold standard for procedures requiring osteogenic mechanisms of healing. This study investigates the utility of muscle-derived stem cells as a cellular therapy for definitive bone regeneration through a form of neo-osteogenesis. Methods: Adipose-derived stem cell, bone marrow-derived mesenchymal stem cell, and muscle-derived stem cell populations were isolated separately from C57BL/6 murine tissues and supplemented with collagen scaffolding with or without bone morphogenetic protein-2 to compare relative osteogenic potency and ultrastructure organization in both two-and three-dimensional systems. Parallel populations were bound to a deployable collagen implant within a syngeneic murine cranial defect model. Results: Although all populations provided and maintained mesenchymal stem cell multilineage capacity, adipose-derived stem cell-and bone marrow-derived mesenchymal stem cell-enriched constructs were capable of forming small bone aggregates. Defects receiving muscle-derived stem cells self-assembled a form of organized corticocancellous structures within two-and three-dimensional in vitro systems and within the in vivo model. Muscle-derived stem cells also augmented healing, implant angiogenesis, and diploic space formation. Conclusion: Muscle-derived stem cell-enriched implants appear to provide an autologous response to current industry-derived products and an attractive alternative to mesenchymal stem cells for the regeneration of corticocancellous bone and a vascularized diploic space.
AB - Background: Regeneration of functional bone substrate remains a priority in reconstructive surgery especially for patients suffering from complex skeletal defects. Efforts to develop implantable osteoinductive constructs and novel osteoconductive materials remain at the forefront of industry forces and product line development. Despite advancement in clinical practice and bone biology, cancellous autograft remains the gold standard for procedures requiring osteogenic mechanisms of healing. This study investigates the utility of muscle-derived stem cells as a cellular therapy for definitive bone regeneration through a form of neo-osteogenesis. Methods: Adipose-derived stem cell, bone marrow-derived mesenchymal stem cell, and muscle-derived stem cell populations were isolated separately from C57BL/6 murine tissues and supplemented with collagen scaffolding with or without bone morphogenetic protein-2 to compare relative osteogenic potency and ultrastructure organization in both two-and three-dimensional systems. Parallel populations were bound to a deployable collagen implant within a syngeneic murine cranial defect model. Results: Although all populations provided and maintained mesenchymal stem cell multilineage capacity, adipose-derived stem cell-and bone marrow-derived mesenchymal stem cell-enriched constructs were capable of forming small bone aggregates. Defects receiving muscle-derived stem cells self-assembled a form of organized corticocancellous structures within two-and three-dimensional in vitro systems and within the in vivo model. Muscle-derived stem cells also augmented healing, implant angiogenesis, and diploic space formation. Conclusion: Muscle-derived stem cell-enriched implants appear to provide an autologous response to current industry-derived products and an attractive alternative to mesenchymal stem cells for the regeneration of corticocancellous bone and a vascularized diploic space.
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U2 - 10.1097/PRS.0000000000003209
DO - 10.1097/PRS.0000000000003209
M3 - Article
C2 - 28350668
AN - SCOPUS:85016259758
SN - 0032-1052
VL - 139
SP - 893
EP - 905
JO - Plastic and Reconstructive Surgery
JF - Plastic and Reconstructive Surgery
IS - 4
ER -