Yu‑Hsun Changa, b, Kun‑Chi Wuc, Hwan‑Wun Liud, Tang‑Yuan Chub, e, Dah‑Ching Dingb, e*
aDepartment of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, bInstitute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, cDepartment of
Orthopedics, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan, dDepartment of Occupational Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan, eDepartment of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Objective: The present study investigated the therapeutic potential and underlying mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) on joint cartilage destruction induced by monosodium iodoacetate (MIA) in mice. Materials and Methods: HUCMSCs were tested for mesenchymal stem cell (MSC) characteristics including surface markers by flow cytometry and mesoderm differentiation (adipogenesis, osteogenesis, and chondrogenesis). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Western blot assay were used to evaluate MIA‑induced chondrocyte apoptosis. In the in vivo study, 18 mice were divided into three groups (n = 6 each); normal saline (control), MIA‑treated, and MIA‑treated/HUCMSC‑transplantation. Rota‑Rods tests were used to evaluate MIA‑induced cartilage destruction behaviors in mice. Histological changes in the mice cartilage were examined by immunohistochemistry. Results: HUCMSCs had an immunophenotype similar to bone marrow‑derived MSCs and were able to differentiate into adipocytes, osteocytes, and chondrocytes. Conditioned medium of the HUCMSCs exhibited an anti‑apoptotic effect and inhibited expression of caspase 3 in MIA‑treated chondrocytes. HUCMSC transplantation assisted in recovery from movement impairment (from 30% on day 7 to 115% on day 14) and in regeneration and repair of cartilage damaged by MIA. (International Cartilage Repair Society score: 3.8 in the MIA group vs. 10.2 in the HUCMSC‑treated group); HUCMSC transplantation ameliorated cartilage apoptosis through the caspase 3 pathway in MIA‑induced cartilage destruction in mice. Conclusion: Taken together, these observations suggest that HUCMSC transplantation appears to be effective in protecting cartilage from MIA damage.
Keywords: Apoptosis, Capase3, Human umbilical cord stromal cells, Monosodium iodoacetate, Osteoarthritis
