Le Q, Madhu V, Hart JM, Farber CR, Zunder ER, Dighe AS, Cui Q. Current evidence on potential of adipose derived stem cells to enhance bone regeneration and future projection. World J Stem Cells 2021; 13(9): 1248-1277 [PMID: 34630861 DOI: 10.4252/wjsc.v13.i9.1248]
Corresponding Author of This Article
Quanjun Cui, MD, Attending Doctor, Professor, Surgeon, Department of Orthopaedic Surgery, University of Virginia School of Medicine, 400 Ray C. Hunt Drive, Suite 330, Charlottesville, VA 22903, United States. qc4q@virginia.edu
Research Domain of This Article
Orthopedics
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Sep 26, 2021; 13(9): 1248-1277 Published online Sep 26, 2021. doi: 10.4252/wjsc.v13.i9.1248
Current evidence on potential of adipose derived stem cells to enhance bone regeneration and future projection
Quang Le, Vedavathi Madhu, Joseph M Hart, Charles R Farber, Eli R Zunder, Abhijit S Dighe, Quanjun Cui
Quang Le, Joseph M Hart, Abhijit S Dighe, Quanjun Cui, Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, United States
Vedavathi Madhu, Orthopaedic Surgery Research, Thomas Jefferson University, Philadelphia, PA 19107, United States
Charles R Farber, Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, United States
Charles R Farber, Departments of Public Health Sciences and Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, United States
Eli R Zunder, Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, United States
Author contributions: Dighe AS and Cui Q contributed conception and designed the research; Le Q, Madhu V and Dighe AS contributed literature search, preparation of the first draft, tables and figures; Le Q, Hart JM and Cui Q contributed clinical trials database search and review; Dighe AS, Farber CR, Zunder ER and Cui Q contributed preparation of semifinal draft after reviewing the first draft; all authors wrote, read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Quanjun Cui, MD, Attending Doctor, Professor, Surgeon, Department of Orthopaedic Surgery, University of Virginia School of Medicine, 400 Ray C. Hunt Drive, Suite 330, Charlottesville, VA 22903, United States. qc4q@virginia.edu
Received: March 28, 2021 Peer-review started: March 28, 2021 First decision: May 12, 2021 Revised: May 22, 2021 Accepted: August 18, 2021 Article in press: August 18, 2021 Published online: September 26, 2021 Processing time: 173 Days and 13.7 Hours
Abstract
Injuries to the postnatal skeleton are naturally repaired through successive steps involving specific cell types in a process collectively termed “bone regeneration”. Although complex, bone regeneration occurs through a series of well-orchestrated stages wherein endogenous bone stem cells play a central role. In most situations, bone regeneration is successful; however, there are instances when it fails and creates non-healing injuries or fracture nonunion requiring surgical or therapeutic interventions. Transplantation of adult or mesenchymal stem cells (MSCs) defined by the International Society for Cell and Gene Therapy (ISCT) as CD105+CD90+CD73+CD45-CD34-CD14orCD11b-CD79αorCD19-HLA-DR- is being investigated as an attractive therapy for bone regeneration throughout the world. MSCs isolated from adipose tissue, adipose-derived stem cells (ADSCs), are gaining increasing attention since this is the most abundant source of adult stem cells and the isolation process for ADSCs is straightforward. Currently, there is not a single Food and Drug Administration (FDA) approved ADSCs product for bone regeneration. Although the safety of ADSCs is established from their usage in numerous clinical trials, the bone-forming potential of ADSCs and MSCs, in general, is highly controversial. Growing evidence suggests that the ISCT defined phenotype may not represent bona fide osteoprogenitors. Transplantation of both ADSCs and the CD105- sub-population of ADSCs has been reported to induce bone regeneration. Most notably, cells expressing other markers such as CD146, AlphaV, CD200, PDPN, CD164, CXCR4, and PDGFRα have been shown to represent osteogenic sub-population within ADSCs. Amongst other strategies to improve the bone-forming ability of ADSCs, modulation of VEGF, TGF-β1 and BMP signaling pathways of ADSCs has shown promising results. The U.S. FDA reveals that 73% of Investigational New Drug applications for stem cell-based products rely on CD105 expression as the “positive” marker for adult stem cells. A concerted effort involving the scientific community, clinicians, industries, and regulatory bodies to redefine ADSCs using powerful selection markers and strategies to modulate signaling pathways of ADSCs will speed up the therapeutic use of ADSCs for bone regeneration.
Core Tip: This review systematically examined current progress and future projections of Adipose-derived Stem Cells (ADSCs) use in bone regeneration. Introduction covered the regulatory aspects of stem cell therapy and scientific concerns regarding stem cell use including ADSCs. We then analyze clinical and pre-clinical studies using ADSCs for the treatment of bone defects. We also evaluate the current understanding of ADSC’s surface receptors and therapeutic subpopulations. Overall, we conclude that while mixed outcomes have been reported, a more rigorous definition of ADSCs, selection of osteogenic subpopulations, and understanding of signaling pathways will unleash ADSCs as a powerful tool in bone regeneration.
