Sub-confluent culture of human mesenchymal stromal cells on biodegradable polycaprolactone microcarriers enhances bone healing of rat calvarial defect

From left: Dr Steve Oh, William Birch, Dr Li Jian, Dr Alan Lam


Alan Tin-Lun Lam1, Eileen Jia-Hui Sim1, Asha Shekaran1, Jian Li2, Kim-Leng Teo1, Julian L. Goggi3, Shaul Reuveny1, William R. Birch2 & Steve Kah-Weng Oh1

1 Bioprocessing Technology institute, Agency for Science, Technology and Research (A*STAR), Singapore
2 Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), Singapore
3 Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore

Published in Cytotherapy 2019 21(6): 631-642 (Online Version)


Human mesenchymal stem cells (hMSCs) are of great interest in bone regenerative medicine, due to their potential of forming bone cells. However, traditional hMSCs expansion methods using planar flasks lack of scalability and are limited by labor-intensive handling. Current cell culture methods also rely on enzymatic cell harvesting and may need a subsequent attachment to a scaffold, before transplantation. BTI, in collaboration with IMRE, developed a process using biodegradable microcarriers that are implemented within a scalable hMSCs bioprocessing system, to overcome the above mentioned challenges.

Our study revealed three main findings. (1) the biodegradable microcarriers support hMSCs adhesion and growth at levels better than that on planar flasks. (2) hMSCs cultured on the biodegradable microcarriers induced bone formation in a calvarial defect rat model at levels better than those expanded on planar flasks. (3) 50% sub-confluency on the microcarriers demonstrated better bone formation in the rat model as compared with 100% confluent cultures. This was due to the fact that 50% confluent cultures exhibited higher secretion levels of cytokines for bone formation as compared with 100% confluent cultures.

In summary, compared with planar flask cultures, biodegradable microcarriers cultures provide the benefits of large-scale expansion of cells and are suitable for the direct delivery of cells, in-vivo. This was assessed in experimental rat models, thus demonstrating the use of these cell culture supports for cell delivery. Our study highlights the potential of implanting 50% confluent hMSCs propagated on biodegradable microcarriers as optimal for bone formation. It offers distinct guidelines for the development of improved bone-healing systems, through the culture and delivery of hMSCs with enhanced efficacy and potency, on biodegradable microcarriers.