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Primed Mesenchymal Stem Cells Alter and Improve Rat Medial Collateral Ligament Healing.

ABSTRACT: Cell therapy with mesenchymal stem cells (MSCs) can improve tissue healing. It is possible, however, that priming MSCs prior to implantation can further enhance their therapeutic benefit. This study was then performed to test whether priming MSCs to be more anti-inflammatory would enhance healing in a rat ligament model, i.e. a medial collateral ligament (MCL). MSCs were primed for 48 h using polyinosinic acid and polycytidylic acid (Poly (I:C)) at a concentration of 1 ?g/ml. Rat MCLs were surgically transected and administered 1?×?10(6) cells in a carrier solution at the time of injury. A series of healing metrics were analyzed at days 4 and 14 post-injury in the ligaments that received primed MSCs, unprimed MSCs, or no cells (controls). Applying primed MSCs beneficially altered healing by affecting endothelialization, type 2 macrophage presence, apoptosis, procollagen 1?, and IL-1Ra levels. When analyzing MSC localization, both primed and unprimed MSCs co-localized with endothelial cells and pericytes suggesting a supportive role in angiogenesis. Priming MSCs prior to implantation altered key ligament healing events, resulted in a more anti-inflammatory environment, and improved healing.

SUBMITTER: Saether EE

PROVIDER: S-EPMC4968884 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Primed Mesenchymal Stem Cells Alter and Improve Rat Medial Collateral Ligament Healing.

Saether Erin E EE Chamberlain Connie S CS Aktas Erdem E Leiferman Ellen M EM Brickson Stacey L SL Vanderby Ray R

Stem cell reviews and reports 20160201 1

Cell therapy with mesenchymal stem cells (MSCs) can improve tissue healing. It is possible, however, that priming MSCs prior to implantation can further enhance their therapeutic benefit. This study was then performed to test whether priming MSCs to be more anti-inflammatory would enhance healing in a rat ligament model, i.e. a medial collateral ligament (MCL). MSCs were primed for 48 h using polyinosinic acid and polycytidylic acid (Poly (I:C)) at a concentration of 1 μg/ml. Rat MCLs were surgi ...[more]

PMID: 26530282

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Project description:Background:Injury to the medial collateral ligament (MCL) of the knee joint is the most common ligament injury of the knee. Ligament healing generally takes a long time. Micro-ribonucleic acid (miRNA) is one of the noncoding RNAs and plays a crucial role in physiological function; miRNA (miR)-210 is known as a potent factor of angiogenesis, which is an important initiator of ligament healing. The purpose of this study is to examine the effect of local injection of double-stranded (ds) miR-210 on the healing of the MCL of rat knee joint. Methods:MCLs of Sprague-Dawley rats were cut transversely. After the fascia and skin were sutured, dsmiR-210 or control dsRNA was injected into the injured site of MCL. At 2 weeks and 4 weeks, histological analysis and immunofluorescence staining of vascular endothelial growth factor, isolectin B4, collagen type 1, and Ki67 as well as a mechanical test were performed. Analysis of complementary deoxyribonucleic acid (cDNA) microarray data was performed at 1 week. Results:Histological analysis showed that parallel fibres in the injured site were organised at 2 weeks and became thicker at 4 weeks in the miR-210-treated group, whereas the injured site in controls was filled with loose fibrous tissues and was thinner than that in the miR-210-treated group. The number of blood vessels in the miR-210-treated group was significantly higher than that in controls (p < 0.05), and vascular endothelial growth factor, Ki67, and collagen type 1 in the miR-210-treated group were intensely expressed in the repaired site as compared to the control group. The mechanical test indicated that the ultimate failure load in the miR-210-treated group was significantly higher than that in the control group at 2 weeks. The cDNA microarray analysis showed significant upregulation of genes related to cell proliferation and cell differentiation, and genes involved in negative regulation of apoptosis. Conclusion:This study showed that local injection of dsmiR-210 could accelerate MCL healing in rat, which is likely due to stimulation of angiogenesis at the healing site.

Project description:PurposeTo quantify intraoperative joint space widening afforded by the outside-in, percutaneous release of the medial collateral ligament (MCL) and to evaluate its impact on medial compartment width and functional outcomes at 6-week follow-up for patients undergoing a partial medial meniscectomy without postoperative bracing.MethodsPatients with posteromedial meniscus tears and no evidence of ipsilateral knee pathology, undergoing partial medial meniscectomy, were enrolled. Intraoperatively, medial compartment width was quantified with fluoroscopy before and after the percutaneous MCL release with an 18-gauge spinal needle proximal to the joint line. At 6-week follow-up, valgus stress radiographs re-evaluated medial compartment width. International Knee Documentation Committee (IKDC) and Patient-Reported Outcomes Measurement Information System (PROMIS) scores were completed preoperatively and at 6-week follow-up to evaluate functional outcomes. A paired sample t test performed at a 95% confidence interval (CI) was used to compare these variables.ResultsForty-two patients, mean (± standard deviation) age 55.3 ± 10.7 years, were available for analysis of intraoperative medial compartment widening. Medial compartment width increased from 5.95 ± 1.32 to 11.09 ± 1.74 mm intraoperatively after MCL release. At 6-week follow-up, radiographic assessment demonstrated a mean medial compartment width of 5.85 ± .99 mm, which represented an insignificant change compared with the preoperative value (CI -0.68 to .33, P = .474). PROMIS and IKDC scores significantly improved from baseline, with increases of 6.9 ± 12.4 (CI 2.0 to 11.8, P = .008) and 11.7 ± 17.8 (CI 4.7 to 18.8, P = .002), respectively.ConclusionsPercutaneous MCL release during knee arthroscopy improves visualization and facilitates instrumentation by providing an almost 2× wider working space within the medial tibiofemoral joint. In this study, the performance of percutaneous MCL release did not result in any complications. Radiographic and clinical resolution of iatrogenic laxity was demonstrated by 6-weeks postoperatively, without the use of postoperative bracing.Level of evidenceIV, therapeutic case series.

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Primed Mesenchymal Stem Cells Alter and Improve Rat Medial Collateral Ligament Healing.

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Primed Mesenchymal Stem Cells Alter and Improve Rat Medial Collateral Ligament Healing.

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