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- Title
Clumps of Mesenchymal Stem Cell/Extracellular Matrix Complexes Generated with Xeno-Free Conditions Facilitate Bone Regeneration via Direct and Indirect Osteogenesis.
- Authors
Motoike, Souta; Kajiya, Mikihito; Komatsu, Nao; Horikoshi, Susumu; Ogawa, Tomoya; Sone, Hisakatsu; Matsuda, Shinji; Ouhara, Kazuhisa; Iwata, Tomoyuki; Mizuno, Noriyoshi; Fujita, Tsuyoshi; Ikeya, Makoto; Kurihara, Hidemi
- Abstract
Three-dimensional clumps of mesenchymal stem cell (MSC)/extracellular matrix (ECM) complexes (C-MSCs) consist of cells and self-produced ECM. We demonstrated previously that C-MSCs can be transplanted into bone defect regions with no artificial scaffold to induce bone regeneration. To apply C-MSCs in a clinical setting as a reliable bone regenerative therapy, the present study aimed to generate C-MSCs in xeno-free/serum-free conditions that can exert successful bone regenerative properties and to monitor interactions between grafted cells and host cells during bone healing processes. Human bone marrow-derived MSCs were cultured in xeno-free/serum-free medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. Then, C-MSCs were transplanted into an immunodeficient mouse calvarial defect model. Transplantation of C-MSCs induced bone regeneration in a time-dependent manner. Immunofluorescence staining showed that both donor human cells and host mice cells contributed to bone reconstruction. Decellularized C-MSCs implantation failed to induce bone regeneration, even though the host mice cells can infiltrate into the defect area. These findings suggested that C-MSCs generated in xeno-free/serum-free conditions can induce bone regeneration via direct and indirect osteogenesis.
- Subjects
MESENCHYMAL stem cells; BONE regeneration; EXTRACELLULAR matrix; BONE growth; COMPLEX matrices; BONE cells
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 16, p3970
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20163970