PMID- 29035380 OWN - NLM STAT- MEDLINE DCOM- 20181217 LR - 20230216 IS - 1530-0307 (Electronic) IS - 0023-6837 (Linking) VI - 98 IP - 1 DP - 2018 Jan TI - Mixed cell therapy of bone marrow-derived mesenchymal stem cells and articular cartilage chondrocytes ameliorates osteoarthritis development. PG - 106-116 LID - 10.1038/labinvest.2017.117 [doi] AB - Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage defect model implanted subcutaneously in mice; and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats. The mixed cells were compared with monocultures of BMSCs and ACCs. In all three experimental models there was significantly enhanced cartilage regeneration and decreased fibrosis in the mixed BMSCs+ACCs group compared with the monocultures. Molecular analysis showed a reduction in vascularization and hypertrophy, coupled with higher chondrogenic gene expression resulting from the BMSCs+ACCs treatment. Together, our data suggest that mixed BMSCs+ACCs treatment is highly chondro-protective and is more effective in regenerating damaged cartilage in both the ex vivo cartilage defect and post-trauma OA disease models. The results from this approach could potentially be used for regeneration of cartilage in OA patients. FAU - Prasadam, Indira AU - Prasadam I AD - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. FAU - Akuien, Akoy AU - Akuien A AD - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. FAU - Friis, Thor E AU - Friis TE AD - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. FAU - Fang, Wei AU - Fang W AD - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. AD - School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China. FAU - Mao, Xinzhan AU - Mao X AD - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. AD - Department of Orthopaedic Surgery, The Second Xiangya Hospital, Changsha, China. AD - Department of Rheumatism, The Xiangya Hospital, Central-South University, Changsha, China. FAU - Crawford, Ross W AU - Crawford RW AD - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. AD - Prince Charles Hospital, Brisbane, QLD, Australia. FAU - Xiao, Yin AU - Xiao Y AD - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171016 PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 SB - IM MH - Aged MH - Animals MH - *Bone Marrow Transplantation MH - Cartilage, Articular/blood supply/*metabolism/pathology/physiology MH - Cell Differentiation MH - Cells, Cultured MH - Chondrocytes/metabolism/pathology/*transplantation MH - Coculture Techniques MH - *Disease Models, Animal MH - *Gene Expression Regulation MH - Humans MH - Hypertrophy/metabolism/pathology/prevention & control MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mice, Inbred NOD MH - Mice, SCID MH - Neovascularization, Pathologic/metabolism/pathology/prevention & control MH - Osteoarthritis, Knee/metabolism/pathology/physiopathology/*therapy MH - Proof of Concept Study MH - Rats, Wistar MH - Regeneration MH - Transplantation, Heterologous EDAT- 2017/10/17 06:00 MHDA- 2018/12/18 06:00 CRDT- 2017/10/17 06:00 PHST- 2017/05/08 00:00 [received] PHST- 2017/08/14 00:00 [revised] PHST- 2017/09/14 00:00 [accepted] PHST- 2017/10/17 06:00 [pubmed] PHST- 2018/12/18 06:00 [medline] PHST- 2017/10/17 06:00 [entrez] AID - S0023-6837(22)01156-4 [pii] AID - 10.1038/labinvest.2017.117 [doi] PST - ppublish SO - Lab Invest. 2018 Jan;98(1):106-116. doi: 10.1038/labinvest.2017.117. Epub 2017 Oct 16.