Age-Related Differences in Anterior Cruciate Ligament Remnant Vascular-Derived Cells
The American Journal of Sports Medicine
Published online on April 11, 2014
Abstract
The anterior cruciate ligament (ACL) does not heal spontaneously after injury, and patients of different ages respond differently to treatment. CD34+ stem/progenitor cells derived from the ACL remnant and associated tissues contribute to tendon-bone healing, but the relationship between age and the ACL’s healing potential has not been clarified.
The ACL remnant and associated tissues from adolescent patients have more CD34+ cells, and this population of cells from younger patients exhibits a higher potential for proliferation and differentiation in vitro.
Descriptive laboratory study.
Ruptured ACL remnants and associated tissues were harvested from 28 patients (mean age, 24.6 ± 1.6 years) who had undergone primary arthroscopic ACL reconstruction. Patients were divided into 3 patient groups by age: 10-19 years (teens group; n = 10), 20-29 years (20s group; n = 10), and ≥30 years (30s group; n = 8). The ACL remnant cells were characterized using fluorescence-activated cell sorting (FACS). Expansion potential was evaluated using population doubling (PD), and multilineage differentiation potential was assessed and compared.
The FACS analysis showed numerous CD34+ cells in the teens group compared with the 30s group (mean, 25.4% ± 7.9% vs 16.9% ± 3.9%, respectively; P = .044). The PD results indicated that the teens group had a significantly higher expansion potential than the 30s group at passage 3 (mean, 3.3 ± 0.2 vs 2.8 ± 0.2, respectively; P = .039). Young ACL remnant cells had a higher potential for osteogenic differentiation according to alkaline phosphatase activity (teens group, 169.5 ± 37.9 x 10 ng/mL vs 30s group, 64.9 ± 14.6 x 10 ng/mL; P = .029) and osteocalcin gene expression (teens group, 1.0 ± 0.25 vs 30s group, 0.39 ± 0.01; P = .01). In addition, the teens group displayed a higher differentiation potential to angiogenic lineages (acetylated low-density lipoprotein/Ulex europaeus lectin-stained cell counts) than other groups (teens group, 15.9 ± 1.9 vs 20s group, 8.9 ± 1.3 [P = .04]; teens group, 15.9 ± 1.9 vs 30s group, 7.2 ± 1.5 [P = .008]) and also tube length (teens group, 6939 ± 470 μm vs 30s group, 4119 ± 507 μm; P = .009).
The ACL remnants of adolescent patients had more CD34+ cells, and those cells had a higher potential for proliferation and multilineage differentiation in vitro.
During remnant-preserving or remnant-transplanted ACL reconstruction, surgeons should consider the patient’s age when predicting the healing potential.