A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Newborn Umbilical Cord Mesenchymal Stem Cells in Bone Regeneration : Plastic and Reconstructive Surgery

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A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Newborn Umbilical Cord Mesenchymal Stem Cells in Bone Regeneration

Stanton, Eloise BA1,2,3; Feng, Jifan PhD1; Kondra, Katelyn MD2,3; Sanchez, Janet BS1; Jimenez, Christian BS2,3; Brown, Katherine S. PhD4; Skiles, Matthew L. PhD4; Urata, Mark M. MD, DDS1,2,3,5; Chai, Yang DDS, PhD1,5; Hammoudeh, Jeffrey A. MD, DDS2,3,5

Author Information

1. Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033

2. Keck School of Medicine, University of Southern California, Los Angeles, CA 90033

3. Division of Plastic and Maxillofacial Surgery, Children’s Hospital Los Angeles, Los Angeles, CA 90033

4. Research and Development, Cbr Systems, Inc., a CooperSurgical company, Tucson, AZ

5. Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089

Financial Disclosure Statement: Cbr Systems, Inc. (Cord Blood Registry ®, CBR), a CooperSurgical company. KS Brown and ML Skiles receive payment as employees of CooperSurgical.

Corresponding Author: Jeffrey A. Hammoudeh, MD, DDS, FACS Division of Plastic and Maxillofacial Surgery Children’s Hospital Los Angeles 4650 West Sunset Boulevard, Mailstop 96 Los Angeles, CA 90027 E-mail: [email protected]

Plastic and Reconstructive Surgery ():10.1097/PRS.0000000000010754, May 24, 2023. | DOI: 10.1097/PRS.0000000000010754

Abstract

Background: 

The standard graft material for alveolar cleft repair (ACR) is autogenous iliac crest. However, a promising alternative potential graft adjunct - newborn human umbilical cord mesenchymal stem cells (h-UCMSC) - has yet to be explored in vivo. Their capacity for self-renewal, multipotent differentiation, and proliferation allows h-UCMSC to be harnessed for regenerative medicine. Our study seeks to evaluate the efficacy of using tissue-derived h-UCMSC and their osteogenic capabilities in a murine model to improve ACR.

Methods: 

Foxn1 mice were separated into three groups with the following calvarial defects: (1) no-treatment (empty defect; n=6), (2) poly (D,L-lactide-co-glycolide) (PLGA) scaffold (n=6), and (3) h-UCMSC with PLGA (n=4). Bilateral 2-mm diameter parietal bone critical-sized defects were created using a dental drill. Micro-CT imaging occurred at 1, 2, 3, and 4 weeks postoperatively. The mice were euthanized 4 weeks postoperatively for RNAscope analysis, immunohistochemistry, and histology.

Results: 

No mice experienced complications during the follow-up period. Micro-CT and histology demonstrated that the no-treatment (1) and PLGA-only (2) defects remained patent without significant defect size differences across groups. In contrast, the h-UCMSC with PLGA group (3) had significantly greater bone fill on micro-CT and histology.

Conclusions: 

We demonstrate a successful calvarial defect model for the investigation of h-UCMSC-mediated osteogenesis and bone repair. Furthermore, evidence reveals that PLGA alone has neither short-term effects on bone formation nor any unwanted side effects, making it an attractive scaffold. Further investigation using h-UCMSC with PLGA in larger animals is warranted to advance future translation to patients requiring ACR.

Clinical Relevance Statement: 

Our results demonstrate a successful murine calvarial defect model for the investigation of h-UCMSC-mediated osteogenesis and bone repair and provide preliminary evidence for the safe and efficacious use of this graft adjunct in alveolar cleft repair.

Copyright © 2023 by the American Society of Plastic Surgeons

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