Finding the right support
Scaffolds that are able to support stem-cell proliferation and differentiation in culture may not have the same effects in the human body
Published online 19 January 2011
Stem cells have attracted much media attention because of their potential in regenerative medicine. For example, many studies have demonstrated the possibility of using mesenchymal stem cells (MSCs)—stem cells derived from bone marrow—to grow skin, muscle, bone and connective tissues in culture. The general approach involves the use of porous biomaterials, or scaffolds, to support the proliferation and differentiation of MSCs. However, Simon Cool at the A*STAR Institute of Medical Biology and National University of Singapore and co-workers have now discovered that some scaffolds may perform differently in therapeutic applications than they do in experiments1.
“Human MSCs are being trialed for the treatment of trauma as well as a plethora of acute and chronic diseases,” says Cool. “With the amount of investment and clinical activities, there is a growing expectation that physicians will be using MSCs on patients within the next five years. For this reason, scientists are urgently searching for scaffolds that promote the vigorous growth of MSCs in the human body.”
Previous studies have used polycaprolactone and tricalcium phosphate (PCL-TCP) scaffolds (pictured) for growing bone tissue. The composite material is highly porous and biodegradable, yet sturdy enough to withstand pressure in the human body. The researchers investigated the regenerative capacity of human MSCs seeded in PCL-TCP scaffolds and compared the difference in culture and in rats with broken femurs.
MSCs flourished on the PCL-TCP matrix, and after several weeks these cells had colonized the scaffold and began to exhibit clear signs of developing into bone tissue, including the expression of differentiation-specific genes and the accumulation of calcium deposits. This process could be further accelerated by cultivating cells with chemicals that specifically stimulate bone-cell maturation.
For their implantation experiments, the researchers specifically chose a sample of donor cells that exhibited the most orthodox MSC-like behavior. However, after three weeks, only three of the six recipient animals displayed regeneration at the implantation site, and the other rats showed no evidence of new femoral bone growth. Moreover, the new bone tissue only covered half of the area that needed treatment.
The findings demonstrate that sometimes in vitro data are not sufficient to predict the growth of stem cells in scaffolds in vivo. “When we started out, we expected to find strong correlation between how MSCs performed in culture and their ability to heal tissue when transplanted,” says Cool. “Instead, our research highlighted the need to develop better benchmarking standards prior to transplantation.”
The A*STAR-affiliated researchers contributing to this research are from the Institute of Medical Biology
- Rai, B. et al. Differences between in vitro viability and differentiation and in vivo bone-forming efficacy of human mesenchymal stem cells cultured on PCL-TCP scaffolds. Biomaterials 31, 7960–7970 (2010). | article