Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future

Abstract

New regenerative treatment strategies are being developed for intervertebral disc degeneration of which the implantation of various cell types is promising. All cell types used so far require in vitro expansion prior to clinical use, as these cells are only limited available. Adipose-tissue is an abundant, expendable and easily accessible source of mesenchymal stem cells. The use of these cells therefore eliminates the need for in vitro expansion and subsequently one-step regenerative treatment strategies can be developed. Our group envisioned, described and evaluated such a one-step procedure for spinal fusion in the goat model. In this review, we summarize the current status of cell-based treatments for intervertebral disc degeneration and identify the additional research needed before adipose-derived mesenchymal stem cells can be evaluated in a one-step procedure for regenerative treatment of the intervertebral disc. We address the selection of stem cells from the stromal vascular fraction, the specific triggers needed for cell differentiation and potential suitable scaffolds. Although many factors need to be studied in more detail, potential application of a one-step procedure for intervertebral disc regeneration seems realistic.

Figure 1

Concept of a one-step surgical procedure. The surgery starts with harvesting of the adipose tissue, followed by a split procedure. The surgeon continues the surgery, whereas the tissue engineer isolates the stem cell-containing cell population from the adipose tissue, treat the cells to induce differentiation into the proper phenotype, and seeds the stimulated cells on the scaffold. The surgeon then implants the scaffold containing the stem cells, and finishes the surgery. The whole procedure takes approximately two hours.

Figure 2

Effects of micromass NP cells on the differentiation related gene expression of ASCs in monolayer or micromass. A: NP cells only significantly down-regulated the gene expression of osteopontin and type I collagen in monolayer ASCs, but they significantly up-regulated the gene expression of aggrecan and concomitantly down-regulate the gene expression of osteopontin, type I collagen and PPAR-γ in micromass ASCs; the data are expressed as means ± sd, n = 3; the dash line represents time-point zero. B: Gene expression of type II collagen was only induced in the group where both ASCs and NP cells were cultured in micro masses. *: Significant difference (p < 0.05). NP cells: Nucleus pul-posus cells; ASCs: Adipose mesenchymal stem cells. Mono: monolayer, MM: micro mass. AGG: aggrecan, COL II: type II collagen, COL I: type I collagen, PPAR-γ: peroxisome proliferator-activated receptor gamma. (Reprinted from Biochemical and Biophysical Research Communications, vol. 359, Lu ZF, Zandieh Doulabi B, Wuisman PI, Bank RA and Helder MN, Differentiation of adipose stem cells b ynucleus pulposus cells: configuration effects., p. 991–6, 2007 with permission from Elsevier.)

Figure 3

Figure A shows a confocal image of SVF cells attaching to the inner pore of a 70:30 Poly(D,L-lactide-co-caprolac-tone) scaffold. After allowing the heterogeneous mixture of SVF cells to attach to the scaffold for one hour, cells were fixated and stained for CD34 (green). The nuclei of all attached cells were stained with propidium iodide as a counter stain (red). Figure B shows the exact same picture in which the scaffold was not visualized for clarity reasons.