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

Abstract

Histological and cytological observations of the human anterior cruciate ligament (ACL) had been described, but the differentiation potency based on their location is still unknown. To determine and compare proliferation and differentiation potential of cells derived from distal and middle thirds of the ACL remnant, ACL remnant was initially marked at the distal third (within 10 mm from the tibial insertion) and middle third (between 10-20 mm from the tibial insertion) and then dissected. Both the middle and distal third regions of ACL remnant were analyzed using CD34 + cell counting. Cell proliferation rate did not differ in both middle and distal third regions of ACL remnant, but they showed different characteristics in cell differentiation depending on their location. The distal third region of the ACL remnant had a tendency for chondrogenic differentiation with higher expression of CD34 + cells. On the other hand, the middle third region of ACL remnant had a strong tendency for osteogenic and ligamentous differentiation. Characteristics of the ACL remnant tissues should be considered when performing remnant-preserving or harvesting ACL remnants for tissue engineering. Anterior cruciate ligament reconstruction (ACLR) is one of the most common surgical procedures in the field of orthopaedic sports medicine, with more than 130,000 procedures performed annually in the United States alone 1,2. It has been well documented that a completely ruptured ACL does not spontaneously heal because of poor vascular supply and an unfavourable intra-articular environment 3. Given the importance of its biomechanical function, surgical treatment is generally accepted as the standard procedure for restoring knee stability. In most cases, non-augmented primary repair has been unsuccessful, and therefore ACL reconstruction is required 1,4,5. For surgical success, ACLR requires tendon graft healing in a surgically created bone tunnel and maturation (i.e., ligamentization) of the graft substance 4,6-9. Indeed, the lack of vascularity within the tendon graft induces degeneration or micro ruptures during the early postoperative period 10. To overcome these issues, tissue engineering using stem cells has been widely explored as a means to achieve early graft healing, tendon regeneration, and bone integration. Recently, reports have shown that ruptured human ACL tissues can possess numerous vascular-derived stem cells and that ACL-derived CD34 + cells can promote healing and have high expansion and multilineage differentiation potential 7,11-13. Mifune et al. 14 demonstrated that ACL-derived CD34 + cells contributed to tendon-bone healing after ACLR via angiogenesis and osteogenesis enhancements 15. Furthermore, Matsumoto et al. 16 found that incorporation of ruptured ACL tissues in autologous grafts reduced tunnel enlargement in ACLR 16,17. However, with regard to their clinical application, potential advantages of remnant-derived stem cells are still questionable. Histological observations of the uninjured human ACL have shown a differe...

Mechanoreceptor analysis on femoral and tibial site remnant of anterior cruciate ligament injury using immunohistochemistry

“…Many studies of histology and the potential of ACL remnant in humans have been carried out. A previous study by Lee et al [ 19 ] evaluated the histology and cytology of ACL remnant based on their location. They discuss the potential for differentiation in the distal third of the remnant ACL (10 mm from the insertion in the tibia), such as the medial (10–20 mm).…”

Does remnant tissue preservation in anterior cruciate ligament reconstruction influence the creation of the rectangular femoral tunnel?

“…Some studies have reported that the remnant tissue expressed various types of collagen, CD34+ cells, and other genes. 38,39 However, it is still unclear whether these biological effects influence clinical outcomes.…”

Blocking TNFα attenuates progressive cartilage matrix degradation in inflammatory arthritis

“…Chondrogenic differentiation of chondrocytes with pellet culture. The 'pellet culture' method was performed as previously described (25). Briefly, primary chondrocytes (2x10 5 ) were collected following centrifugation at 25˚C for 3 min at 441 x g, replaced and cultured in chondrogenic medium with distilled water or TNFα for 4 weeks.…”