Three-Dimension Culture Of Mesenchymal Stem Cells With Nano-Fiber Scaffold Induces Chondrogenesis and Osteogenesis

Kunihiro Yamaoka¹, Koshiro Sonomoto¹, Xiangmei Zhang¹, Masahiro Kondo¹, Shunsuke Fukuyo¹, Makoto Satake², Hiroaki Kaneko², Kazuhisa Nakano¹, Yosuke Okada¹ and Yoshiya Tanaka¹, ¹The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, ²The Third Laboratory, Integrative Technology Research Institute, Teijin Limited, Tokyo, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: chondrocytes, mesenchymal stem cells and osteoblasts

Session Information

Title: Biology and Pathology of Bone and Joint (Bone and Arthritis)

Session Type: Abstract Submissions (ACR)

Background/Purpose: Development of biologics has made remission a realistic treatment goal in treatment of rheumatoid arthritis (RA). However, once bone or cartilage is destructed treatment tool aiming joint repair do not exist. On that note, treatment strategy for established RA is requisite. We have previously shown that mesenchymal stem cells (MSCs) suppress osteoclastogenesis and also differentiate into osteoblasts under the presence of inflammation. Therefore, in addition to its immunosuppressive effect, we believe that MSCs is a useful tool to develop treatment aiming joint repair. We have evaluated the applicability of poly-lactic fiber (Nano-fiber) scaffold.

Methods: MSCs from healthy donor, osteoarthritis (OA) or RA was seeded onto Nano-fiber (Nano-MSCs) and cultured in MSCs growth media (MSCGM) or osteoblast induction media (OIM) for 7~56 days. Differentiation markers for osteoblasts (RUNX2, Osteocalcin, meneralization), osteocytes (Dmp-1, MEPE) and chondrocytes (SOX9, Type II collagen, COL10A1, proteoglycan production) were evaluated.

Results: Healthy Nano-MSCs culture in OIM for 28 days induced runt-related gene 2 (RUNX2) expression and mineralization with positive Safranin O staining suggesting that Nano-hMSC induced osteoblastogenesis and chondrogenesis in parallel. When healthy Nano-MSCs was cultured in MSCGM, Safranin O positive cells and chondrocyte markers were detectable from day 14. Mineralization and osteocyte marker expression were observed on day 56 with osteocyte-like shape under the scan electron microscopy. Similar results were observed with MSCs from RA and OA patients. However, MSCs seeded onto culture flask with MSCGM did not express any of these differentiation markers. The non-canonical wingless-type MMTV integration site (Wnt) signaling pathway was suggested to play a role in these phenomena.

Conclusion: Our results suggest that MSCs simutaneously differentiate into chondrocytes, osteoblasts and osteocytes when seeded onto Nano-fiber scaffold without specific stimulation for differentiation. Since Nano-fiber is bioabsorbable, its use in combination with MSCs would be a useful tool for regeneration of destructed joints in RA and OA patients.

Disclosure:

K. Yamaoka,
None;

K. Sonomoto,
None;

X. Zhang,
None;

M. Kondo,
None;

S. Fukuyo,
None;

M. Satake,

teijin,

H. Kaneko,

teijin,

K. Nakano,
None;

Y. Okada,
None;

Y. Tanaka,

BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, Abbvie, Daiichi-Sankyo,

UCB, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei,

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