Anterior cruciate ligament remnant tissue harvested within 3-months after injury predicts higher healing potential

Abstract

BackgroundNo study has examined the possible factors associated with different characteristics of stem-like cells derived from anterior cruciate ligament (ACL) remnants. And the purpose of the study is to elucidate whether demographic factors are associated with healing potential of stem-like cells derived from the ACL remnants tissue.MethodsThirty-six ACL remnants were harvested from patients who received primary arthroscopic ACL reconstruction. Interval from injury to surgery, age, sex, and combined meniscal or chondral injuries were analyzed. Cells were isolated from remnant tissues and their healing potential was evaluated by: 1) characterization of surface markers (CD34, CD44, CD45, CD146, CD29, and Stro-1), 2) cell expansion, 3) osteogenic differentiation, and 4) endothelial differentiation. Finally, using multivariable logistic regression to evaluate the relation between demographic factors and healing potential parameters. Adjusted odds ratios (OR) were calculated, and the significant difference was set at p < 0.05.ResultsACL remnant tissue harvested less than 90 days after injury predicted higher fractions of stem-like cells [CD34+ (OR = 6.043, p = 0.025), CD44 + (OR = 8.440, p = 0.011), CD45+ (OR = 16.144, p = 0.015), and CD146+ (OR = 9.246, p = 0.015)] and higher expansion potential (passage 3: OR = 9.755, p = 0.034; passage 10: OR = 33.245, p = 0.003). Regarding osteogenic differentiation, higher gene expression of Osteocalcin (OR = 22.579, p = 0.009), Alkaline phosphatase (OR = 6.527, p = 0.022), and Runt-related transcription factor 2 (OR = 5.247, p = 0.047) can also be predicted. Younger age predicted higher CD34+ levels (20 ≤ age <30 years, OR = 2.020, p = 0.027) and higher expansion potential at passage 10 (10 ≤ age <20 years, OR = 25.141, p = 0.026). There was no significant relation found between meniscal or chondral injuries and ACL healing potential.ConclusionOur results indicated that the ACL remnant tissue harvested within 3-months after injury yields higher healing potential, suggesting early surgical intervention may achieve better clinical results.

The Effect of Remnant Tissue Preservation in Anatomic Double-Bundle ACL Reconstruction on Knee Stability and Graft Maturation

“…Recently, there has been focus on ACL remnant tissue, which is usually resected at the time of ACL reconstruction 6 because it may help accelerate the remodeling phase of the graft, with its proprioceptive mechanoreceptors potentially providing a source of reinnervation. [7][8][9][10][11] Several investigators have used animal models to investigate the effectiveness of reinnervation when ACL remnant tissue was preserved, reporting better results compared with those using the conventional procedure. For example, preservation of ACL remnant tissue may accelerate the remodeling of grafted tendon and enhance the bone-tendon healing of the bone tunnel after ACL reconstruction.…”

Anterior cruciate ligament remnant cells have different potentials for cell differentiation based on their location

“…Although research on mechanoreceptor regeneration and its function in an ACL-reconstructed knee is lacking, surgeons tend to preserve some of the tibial ACL remnants in order to improve knee function. Zhang et al 25 performed a randomized controlled trial for remnant-preserving ACLR in order to investigate the effect of remnant preservation on tibial tunnel enlargement using a hamstring autograft. The authors found that tibial remnant preservation can resist tibial tunnel enlargement, demonstrating that the remnant tibial side has tendon-bone healing potential.…”

“…The healing potential of the remnant is influenced by a number of different factors, which suggests that the characteristics of individuals should be considered 18,25,[31][32][33][34] . Nakano et al 31 found that ACL-derived cells from a younger group enhanced bone-tendon healing in an immunodeficient ACL reconstruction rat model.…”

“…Naraoka et al 32 demonstrated a time-dependent alteration in gene expression patterns that decrease over time in ruptured ACL tissue. Moreover, Zhang et al 25 reported that ruptured ACL remnants extracted during the early phase (within three months) of ACL injury displayed a higher proliferation and multilineage differentiation potential than remnants extracted during the chronic phase. The authors observed that CD34 + cells were more prevalent in ACL remnants from an early phase of injury compared with those from the chronic phase.…”

Anterior cruciate ligament remnant and its values for preservation

“… 45 That authors' group also revealed that the ACL remnant tissue harvested within 3 months after injury yields higher healing potential, suggesting that early surgical intervention may achieve better clinical results. 46 …”