Systemic DKK1 neutralization enhances human adipose-derived stem cell mediated bone repair. (30th December 2020)

• Record Type: Journal Article
• Authors: Negri, Stefano; Wang, Yiyun; Sono, Takashi; Qin, Qizhi; Hsu, Ginny Ching-Yun; Cherief, Masnsen; Xu, Jiajia; Lee, Seungyong; Tower, Robert J.; Yu, Victoria; Piplani, Abhi; Meyers, Carolyn A.; Broderick, Kristen; Lee, Min; James, Aaron W.
• Is Part Of: Stem cells translational medicine. Volume 10:Number 4(2021)
• Page Start: 610
• Page End: 622
• Publication Date: 2020-12-30
• Subjects: adipose stem cell -- adipose stromal cell -- bone healing -- bone repair -- bone tissue engineering -- mesenchymal stem cell -- Wnt signaling; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.20-0293
• Languages: English
• ISSNs: 2157-6564

Abstract

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. Abstract : Systemic anti-DKK1 treatment promotes engrafted stem cell survival, induces vascular ingrowth, and catalyzes bone matrix deposition among human adipose stem cell (ASC) treated femoral segmental bone defects. BM, bone marrow; CB, cortical bone; S, scaffold.