PMID- 30692826 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220401 IS - 1016-3190 (Print) IS - 2223-8956 (Electronic) VI - 31 IP - 1 DP - 2019 Jan-Mar TI - Transplanting human umbilical cord mesenchymal stem cells and hyaluronate hydrogel repairs cartilage of osteoarthritis in the minipig model. PG - 11-19 LID - 10.4103/tcmj.tcmj_87_18 [doi] AB - OBJECTIVES: Osteoarthritis (OA) is a chronic disease of degenerative joints. Mesenchymal stem cells (MSCs) have been used for cartilage regeneration in OA. We investigated the therapeutic potential of human umbilical cord-derived MSCs (HUCMSCs) with hyaluronic acid (HA) hydrogel transplanted into a porcine OA preclinical model. MATERIALS AND METHODS: The HUCMSCs were characterized with respect to morphology, surface markers, and differentiation capabilities. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to examine gene expressions in a HUCMSC-HA coculture. Two healthy female minipigs weighing 30-40 kg and aged approximately 4 months were used in this large animal study. A full-thickness chondral injury was created in the trochlear groove of each of the pig's rear knees. After 3 weeks, a second osteochondral defect was created. Then, 1.5 mL of a HUCMSC (5 x 10(6) cells) and HA composite (4%) was transplanted into the chondral-injured area in the right knee of each pig. Using the same surgical process, an osteochondral defect (untreated) was created in the left knee as a control. The pigs were sacrificed 12 weeks after transplantation. Macroscopic and microscopic histologies, qRT-PCR, and immunostaining evaluated the degree of chondral degradation. RESULTS: The HUCMSCs exhibited typical MSC characteristics, including spindle morphology, expression of surface markers (positive for CD29, CD4, CD73, CD90, and human leukocyte antigen [HLA]-ABC; negative for CD34, CD45, and HLA-DR), and multipotent differentiation (adipogenesis, osteogenesis, and chondrogenesis). More extensive proliferation of HUCMSCs was noted with 4% and 25% of HA than without HA. Expression of COL2A1 and aggrecan in the HUCMSC-derived chondrocytes was increased when HA was included. The treated knees showed significant gross and histological improvements in hyaline cartilage regeneration when compared to the control knees. The International Cartilage Repair Society histological score was higher for the treated knees than the control knees. CONCLUSION: Our findings suggest that cartilage regeneration using a mixture of HUCMSCs and HA in a large animal model may be an effective treatment for OA, and this study is a stepping stone toward the future clinical trials. FAU - Wu, Kun-Chi AU - Wu KC AD - Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan. FAU - Chang, Yu-Hsun AU - Chang YH AD - Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan. FAU - Liu, Hwan-Wun AU - Liu HW AD - Department of Occupational Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan. AD - Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan. FAU - Ding, Dah-Ching AU - Ding DC AD - Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan. AD - Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan. AD - Department of Research, Stem Cell Laboratory, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. LA - eng PT - Journal Article PL - China (Republic : 1949- ) TA - Ci Ji Yi Xue Za Zhi JT - Ci ji yi xue za zhi = Tzu-chi medical journal JID - 9514171 PMC - PMC6334562 OTO - NOTNLM OT - Cartilage OT - Human umbilical cord OT - Hyaluronate OT - Mesenchymal stem cells OT - Regeneration COIS- There are no conflicts of interest. EDAT- 2019/01/30 06:00 MHDA- 2019/01/30 06:01 PMCR- 2019/01/01 CRDT- 2019/01/30 06:00 PHST- 2019/01/30 06:00 [entrez] PHST- 2019/01/30 06:00 [pubmed] PHST- 2019/01/30 06:01 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - TCMJ-31-11 [pii] AID - 10.4103/tcmj.tcmj_87_18 [doi] PST - ppublish SO - Ci Ji Yi Xue Za Zhi. 2019 Jan-Mar;31(1):11-19. doi: 10.4103/tcmj.tcmj_87_18.