Systemic DKK1 neutralization enhances human adipose-derived stem cell mediated bone repair
Abstract
Progenitor cells from adipose tissue are able to induce bone repair; however, inconsistent or unreliable efficacy has been reported across preclinical and clinical studies. Soluble inhibitory factors, such as the secreted Wnt signaling antagonists Dickkopf-1 (DKK1), are expressed to variable degrees in human adipose-derived stem cells (ASCs), and may represent a targetable “molecular brake” on ASC mediated bone repair. Here, anti-DKK1 neutralizing antibodies were observed to increase the osteogenic differentiation of human ASCs in vitro, accompanied by increased canonical Wnt signaling. Human ASCs were next engrafted into a femoral segmental bone defect in NOD-Scid mice, with animals subsequently treated with systemic anti-DKK1 or isotype control during the repair process. Human ASCs alone induced significant but modest bone repair. However, systemic anti-DKK1 induced an increase in human ASC engraftment and survival, an increase in vascular ingrowth, and ultimately improved bone repair outcomes. In summary, anti-DKK1 can be used as a method to augment cell-mediated bone regeneration, and could be particularly valuable in the contexts of impaired bone healing such as osteoporotic bone repair.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 30, 2020
- Source ID
- 10.1002/sctm.20-0293
Entities
People
- Aaron W James
- Abhi Piplani
- Carolyn A. Meyers
- Ginny Ching-yun Hsu
- Jiajia Xu
- Kristen Broderick
- Masnsen Cherief
- Min Lee
- Qizhi Qin
- Robert J. Tower
- Seungyong Lee
- Stefano Negri
- Takashi Sono
- Victoria Yu
- Yiyun Wang
Organizations
- American Cancer Society
- Johns Hopkins University
- Musculoskeletal Transplant Foundation
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Dental and Craniofacial Research
- United States Department of Defense
- University of California, Los Angeles
- University of Verona