Isolation, characterization, and differentiation of stem cells for cartilage regeneration

Abstract

The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell sources, including adult and extra-embryonic mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Comparative studies indicate that each cell type has advantages and disadvantages, and while direct comparisons are difficult to make, published data suggest some sources may be more promising for cartilage regeneration than others. In this review, we identify current approaches for isolating and chondrogenically differentiating MSCs from bone marrow, fat, synovium, muscle, and peripheral blood, as well as cells from extra-embryonic tissues, ESCs, and iPSCs. Additionally, we assess chondrogenic induction with growth factors, identifying standard cocktails used for each stem cell type. Cell-only (pellet) and scaffold-based studies are also included, as is a discussion of in vivo results.

Figure 1

Stem cells can be isolated from multiple anatomical locations, encompassing adult and extra-embryonic tissues. The cell sources shown above have all been investigated for cartilage regeneration, although mesenchymal sources have been studied much more than other tissues.

Figure 2

Comparison of reported GAG synthesis amounts per DNA after chondrogenic induction of human-derived cells using box-and-whisker plots. Results were calculated from recent literature by averaging the largest GAG value reported from each study. Cell types and their respective citations include Bone Marrow Stem Cells (BMSC, n=16),, , , , , , , , , , , , , , , Adipose-Derived Stem Cells (ASC, n=11),^{, , , , , , , , , ,} Synovial Membrane-Derived Stem Cells (SDSC, n=5),^{, , , ,} and Embryonic Stem Cells (ESC, n=6).^{, , , , ,}