Spontaneous Differentiation of Human Mesenchymal Stem Cells on Poly-Lactic-Co-Glycolic Acid Nano-Fiber Scaffold

• Published in: PloS one 2016-04, Vol.11 (4), p.e0153231-e0153231
• Main Authors: Sonomoto, Koshiro, Yamaoka, Kunihiro, Kaneko, Hiroaki, Yamagata, Kaoru, Sakata, Kei, Zhang, Xiangmei, Kondo, Masahiro, Zenke, Yukichi, Sabanai, Ken, Nakayamada, Shingo, Sakai, Akinori, Tanaka, Yoshiya
• Format: Article
• Language: English
• Subjects: Acids; Arthritis; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Biocompatibility; Biocompatible Materials - chemistry; Biology and Life Sciences; Biomedical materials; Blotting, Western; Calcification; Cartilage; Cartilage diseases; Case-Control Studies; Cbfa-1 protein; Cell Differentiation; Cell morphology; Cell Proliferation; Cells, Cultured; Chondrocytes; Chondrocytes - cytology; Chondrocytes - metabolism; Chondrogenesis; Chondrogenesis - physiology; Cytokines; Cytology; Dentin; Development and progression; Differentiation; Disease; Endochondral bone; Environmental health; Flow Cytometry; Gene expression; Genetic aspects; Glycolic acid; Humans; Immunosuppressive agents; Internal medicine; Joint diseases; Kinases; Lactic acid; Lactic Acid - chemistry; Medicine; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Nanofibers; Nanofibers - chemistry; Orthopedics; Ossification; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Osteoblastogenesis; Osteoblasts; Osteocalcin; Osteocytes; Osteogenesis; Osteogenesis - physiology; Patients; Phosphoglycoprotein; Physical Sciences; Physiological aspects; Polyglycolic Acid - chemistry; Polylactic Acid-Polyglycolic Acid Copolymer; Polylactide-co-glycolide; Real-Time Polymerase Chain Reaction; Regulators; Repair; Research and Analysis Methods; Reverse Transcriptase Polymerase Chain Reaction; Rheumatoid arthritis; Rheumatology; RNA, Messenger - genetics; Scaffolds; Skin & tissue grafts; Sox9 protein; Stem cells; Stimulation; Tissue Engineering; Tissue Scaffolds
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153231

Mesenchymal stem cells (MSCs) have immunosuppressive activity and can differentiate into bone and cartilage; and thus seem ideal for treatment of rheumatoid arthritis (RA). Here, we investigated the osteogenesis and chondrogenesis potentials of MSCs seeded onto nano-fiber scaffolds (NFs) in vitro and possible use for the repair of RA-affected joints. MSCs derived from healthy donors and patients with RA or osteoarthritis (OA) were seeded on poly-lactic-glycolic acid (PLGA) electrospun NFs and cultured in vitro. Healthy donor-derived MSCs seeded onto NFs stained positive with von Kossa at Day 14 post-stimulation for osteoblast differentiation. Similarly, MSCs stained positive with Safranin O at Day 14 post-stimulation for chondrocyte differentiation. Surprisingly, even cultured without any stimulation, MSCs expressed RUNX2 and SOX9 (master regulators of bone and cartilage differentiation) at Day 7. Moreover, MSCs stained positive for osteocalcin, a bone marker, and simultaneously also with Safranin O at Day 14. On Day 28, the cell morphology changed from a spindle-like to an osteocyte-like appearance with processes, along with the expression of dentin matrix protein-1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE), suggesting possible differentiation of MSCs into osteocytes. Calcification was observed on Day 56. Expression of osteoblast and chondrocyte differentiation markers was also noted in MSCs derived from RA or OA patients seeded on NFs. Lactic acid present in NFs potentially induced MSC differentiation into osteoblasts. Our PLGA scaffold NFs induced MSC differentiation into bone and cartilage. NFs induction process resembled the procedure of endochondral ossification. This finding indicates that the combination of MSCs and NFs is a promising therapeutic technique for the repair of RA or OA joints affected by bone and cartilage destruction.