Stem cell technology for bone regeneration: current status and potential applications

Abstract

Continued improvements in the understanding and application of mesenchymal stem cells (MSC) have revolutionized tissue engineering. This is particularly true within the field of skeletal regenerative medicine. However, much remains unknown regarding the native origins of MSC, the relative advantages of different MSC populations for bone regeneration, and even the biologic safety of such unpurified, grossly characterized cells. This review will first summarize the initial discovery of MSC, as well as the current and future applications of MSC in bone tissue engineering. Next, the relative advantages and disadvantages of MSC isolated from distinct tissue origins are debated, including the MSC from adipose, bone marrow, and dental pulp, among others. The perivascular origin of MSC is next discussed. Finally, we briefly comment on pluripotent stem cell populations and their possible application in bone tissue engineering. While continually expanding, the field of MSC-based bone tissue engineering and regeneration shows potential to become a clinical reality in the not-so-distant future.

Keywords: ASC; DMSC; MSC; bone tissue engineering; mesenchymal stem cell; pericyte.

Figure 1

Representative sites of MSC isolation. Notes: MSC can be isolated from diverse anatomic sites, some of which are depicted here. The most well-studied site of derivation is bone marrow, followed by adipose tissue, dental pulp, and others. MSC are designated by their site of derivation as, for example, BMSC, ASC, and DMSC. Alternatively, purified MSC populations have been named based on their PSC. Although most commonly derived from adipose tissue, PSC may be obtained from diverse human organs using FACS technology. Abbreviations: DMSC, dental pulp mesenchymal stem cells; FACS, fluorescence-activated cell sorting; PSC, perivascular stem cells; BMSC, bone marrow mesenchymal stem cells; ASC, adipose-derived stem cells; MSC, mesenchymal stem cell.

Figure 2

Purification process for PSC. Notes: Although typically isolated from human lipoaspirate, PSC can be extracted from any vascularized organ. After routine liposuction or lipectomy, adipose tissue undergoes enzymatic digestion with collagenase to yield the SVF of adipose tissue. SVF is then purified for PSC via FACS for the differential expression of perivascular markers. As is currently understood, PSC are a bipartite population including CD146+ pericytes and CD34+ adventitial cells. Abbreviations: FACS, fluorescence-activated cell sorting; PSC, perivascular stem cells; SVF, stromal vascular fraction.