Systemic DKK1 neutralization enhances human adipose‐derived stem cell mediated bone repair

Autor: Stefano Negri, Kristen P. Broderick, Robert J. Tower, Aaron W. James, Min Lee, Jiajia Xu, Victoria Yu, Qizhi Qin, Yiyun Wang, Carolyn A. Meyers, Ginny Ching Yun Hsu, Masnsen Cherief, Takashi Sono, Seungyong Lee, Abhi Piplani
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Adipose tissue
Bone healing
Mice
SCID
SCID
Antibodies
03 medical and health sciences
Mice
0302 clinical medicine
Mice
Inbred NOD
Osteogenesis
Tissue Engineering and Regenerative Medicine
Medicine
Animals
Humans
Progenitor cell
lcsh:QH573-671
Bone regeneration
bone tissue engineering
Neutralizing
mesenchymal stem cell
lcsh:R5-920
business.industry
lcsh:Cytology
Stem Cells
Mesenchymal stem cell
adipose stromal cell
Wnt signaling pathway
adipose stem cell
Cell Differentiation
Cell Biology
General Medicine
bone repair
Wnt signaling
Antibodies
Neutralizing
030104 developmental biology
DKK1
Adipose Tissue
Cancer research
Inbred NOD
Intercellular Signaling Peptides and Proteins
Stem cell
bone healing
business
lcsh:Medicine (General)
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Stem Cells Translational Medicine, Vol 10, Iss 4, Pp 610-622 (2021)
Stem Cells Translational Medicine
ISSN: 2157-6564
2157-6580
Popis: 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.
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.
Databáze: OpenAIRE
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