In vivo osteogenic differentiation of human turbinate mesenchymalstem cells in an injectable in situ-forming hydrogel
Jin Seon Kwon a,1, Sung Won Kim b,1, Doo Yeon Kwon a, Seung Hun Park a, A. Reum Son a,Jae Ho Kim a, Moon Suk Kim a,*
a Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea
b Department of Otolaryngology-Head and Neck Surgery, The Catholic University of Korea, College of Medicine, Seoul 137-701, Republic of Korea
Abstract
Human turbinate mesenchymal stromal cells (hTMSCs) are an alternate source of adult stem cells for
regenerative medicine. In this work, we demonstrated that hTMSCs are easily harvested from turbinate
tissue using a minimal surgical procedure. hTMSCs showed positive expression of mesenchymal stem cell
markers and proliferated at a high rate. The specific surface proteins of harvested hTMSCs were relatively
tolerant of ex vivo manipulation in culture. hTMSCs exhibited osteogenic differentiation in vitro in the
presence of osteogenic factors. To examine osteogenic differentiation of hTMSCs in vivo in an injectable
hydrogel, cells were incorporated into a methoxy polyethylene glycolepolycaprolactone block copolymer
(MPEGePCL (MP)) solution simply by mixing. hTMSC-loaded MP solutions exhibited a temperaturedependent
solution-to-gel phase transition. The hTMSC attached and grew well on in vitro- and
in vivo-formed MP hydrogels. hTMSC-loaded MP solutions formed a hydrogel almost immediately upon
injection into animals and the cells remained viable, even after 12 weeks. Injected hTMSCs in in situformed
MP hydrogels differentiated into osteogenic cells, mainly in the presence of osteogenic factors.
Differentiated osteoblasts were identified by Alizarin Red S, von Kossa, and alkaline phosphatase (ALP)
staining, and osteonectin, osteopontin, and osteocalcin mRNA expression. To the best of our knowledge,
this is the first study to show hTMSCs undergoing osteogenic differentiation in in vivo-formed MP
hydrogels. In conclusion, hTMSCs could serve as adult stem cell sources and, when embedded in an in
situ-formed hydrogel, may provide numerous benefits as a noninvasive alternative for bone tissue engineering
applications |
