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Effect of donor age on the proportion of mesenchymal stem cells derived from anterior cruciate ligaments.

ABSTRACT: The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), such as proportion and multilineage potential, can be affected by donor age. However, the qualitative and quantitative features of ACL MSCs isolated from younger and older individuals have not yet been compared directly. This study assessed the phenotypic and functional differences in ACL-MSCs isolated from younger and older donors and evaluated the correlation between ACL-MSC proportion and donor age. Torn ACL remnants were harvested from 36 patients undergoing ACL reconstruction (young: 29.67 ± 10.92 years) and 33 undergoing TKA (old: 67.96 ± 5.22 years) and the proportion of their MSCs were measured. The mean proportion of MSCs was slightly higher in older ACL samples of the TKA group than of the younger ACL reconstruction group (19.69 ± 8.57% vs. 15.33 ± 7.49%, p = 0.024), but the proportions of MSCs at passages 1 and 2 were similar. MSCs from both groups possessed comparable multilineage potentiality, as they could be differentiated into adipocytes, osteocytes, and chondrocytes at similar level. No significant correlations were observed between patient age and MSC proportions at passages 0-2 or between age and MSC proportion in both the ACL reconstruction and TKA groups. Multiple linear regression analysis found no significant predictor of MSC proportion including donor age for each passage. Microarray analysis identified several genes that were differentially regulated in ACL-MSCs from old TKA patients compared to young ACL reconstruction patients. Genes of interest encode components of the extracellular matrix (ECM) and may thus play a crucial role in modulating tissue homeostasis, remodeling, and repair in response to damage or disease. In conclusion, the proportion of freshly isolated ACL-MSC was higher in elderly TKA patients than in younger patients with ACL tears, but their phenotypic and multilineage potential were comparable.

SUBMITTER: Lee DH

PROVIDER: S-EPMC4346262 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Effect of donor age on the proportion of mesenchymal stem cells derived from anterior cruciate ligaments.

Lee Dae-Hee DH Ng Joanne J Kim Sang-Beom SB Sonn Chung Hee CH Lee Kyung-Mi KM Han Seung-Beom SB

PloS one 20150302 3

The characteristics of anterior cruciate ligament (ACL)-derived mesenchymal stem cells (MSCs), such as proportion and multilineage potential, can be affected by donor age. However, the qualitative and quantitative features of ACL MSCs isolated from younger and older individuals have not yet been compared directly. This study assessed the phenotypic and functional differences in ACL-MSCs isolated from younger and older donors and evaluated the correlation between ACL-MSC proportion and donor age. ...[more]

PMID: 25729860

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Project description:BackgroundThe incidence of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) tears in children and adolescents has increased over the past decade, with increasing numbers of ACL and PCL reconstructions in this patient population.PurposeTo evaluate the size and morphology of both the ACL and the PCL by magnetic resonance imaging (MRI) in different pediatric age groups.Study designCross-sectional study; Level of evidence, 3.MethodsMRI examinations of 127 knees (67 female, 60 male; aged 0-18 years) were analyzed retrospectively. The cohort was split into 6 age subgroups, 1 subgroup for every 3 years (minimum 8 patients per subgroup). The following parameters were measured by 2 independent raters at 2 different time points: ACL length, anteroposterior and mediolateral ACL width, sagittal and coronal ACL inclination, inclination of the intercondylar notch, bicondylar width, notch width, coronal ACL and PCL width, PCL length, and sagittal width of the lateral femoral condyle. The following indices, areas, and volumes were calculated: sagittal width of the lateral femoral condyle/PCL length, ACL area and volume, notch width index, ACL width/notch width, PCL width/notch width, ACL width/bicondylar width, and PCL width/bicondylar width. A correlation analysis was performed for patient age, height, weight, and body mass index (BMI).ResultsACL length was between 18 and 37 mm, and ACL width was between 4 and 6 mm. PCL length ranged between 27 and 43 mm, while PCL width was between 7 and 9 mm. Growth of the cruciate ligaments was the most pronounced between the ages of 4 and 12 years. Correlations with size and weight were strong, while BMI correlated slightly with the measurements. Measurements in female patients were slightly larger than in their male counterparts between the ages of 0 and 6 years, while male patients tended to have larger values starting from ages 7 to 9 years. These values were significantly larger in male patients from the ages of 16 to 18 years (P < .05).ConclusionThis study provides normative data on the morphology of pediatric anatomic features in the knee as a basis for age-appropriate and individualized surgical care of ACL and PCL injuries in children and adolescents.

Project description:Background: Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10-100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and in vitro proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important equine demographic of older patients. Objectives: To investigate the effect of donor age on the cellular proliferation of equine BM- and AT-MSCs. Study Design: In vitro study. Methods: BM- and AT-MSCs and dermal fibroblasts (biological control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15-17 months), adult (5-8 years), middle-aged (12-18 years), and geriatric (≥22 years). Proliferation of the cells was tested using an EdU incorporation assay and steady state mRNA levels measured for targeted proliferation, aging, and senescence biomarkers. Results: The cellular proliferation of equine BM- and AT-MSCs declined significantly in the geriatric cohort relative to the younger age groups. Proliferation levels in the two MSC types were equally affected by donor age. Analysis of steady state mRNA levels showed an up-regulation in tumor suppressors, apoptotic genes, and multiple growth factors in MSCs from old horses, and a down-regulation of some pro-cycling genes with a few differences between cell types. Main Limitations: Potential age-dependent differences in cell function parameters relevant to cell-therapy application were not investigated. Conclusions: The cellular proliferation of equine BM- and AT-MSCs declined at advanced donor ages. High levels of in vitro proliferation were observed in both MSC types from horses in the age groups below 18 years of age.

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Effect of donor age on the proportion of mesenchymal stem cells derived from anterior cruciate ligaments.

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Effect of donor age on the proportion of mesenchymal stem cells derived from anterior cruciate ligaments.

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