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Regeneration of Vascularized Corticocancellous Bone and Diploic Space Using Muscle-Derived Stem Cells: A Translational Biologic Alternative for Healing Critical Bone Defects

Lough, Denver M.D., Ph.D.; Swanson, Edward M.D.; Sopko, Nikolai A. M.D., Ph.D.; Madsen, Christopher M.D.; Miller, Devin M.D.; Wang, Howard M.D.; Guo, Qiongyu Ph.D.; Sursala, Srinivas M. D.M.D., M.D., M.P.H.; Kumar, Anand R. M.D.

Plastic & Reconstructive Surgery: April 2017 - Volume 139 - Issue 4 - p 893–905
doi: 10.1097/PRS.0000000000003209
Experimental: Original Articles

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.

Baltimore, Md.

From the Department of Plastic and Reconstructive Surgery, The Johns Hopkins University Hospital.

Received for publication January 9, 2016; accepted August 3, 2016.

Disclosure: None of the authors has a financial interest in any of the products, assays or devices mentioned in the article. Funds provided for this specific project were from The Plastic Surgery Foundation (PSF) Fund and The Johns Hopkins Military & Veterans Health Institute (MVHI).

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This work was supported by THE PLASTIC SURGERY FOUNDATION.

Denver Lough, M.D., Ph.D., Department of Plastic and Reconstructive Surgery, The Johns Hopkins Hospital, 600 North Caroline Street, Baltimore, Md. 21287,, Anand R. Kumar, M.D., Center for Pediatric Craniofacial Surgery and, Department of Plastic and Reconstructive Surgery, The Johns Hopkins Hospital, 600 North Caroline Street, Baltimore, Md. 21287,

©2017American Society of Plastic Surgeons