The Influence of Ruptured Scar Pattern on the Healing Potential of Anterior Cruciate Ligament Remnant Cells

Kirizuki, Shinsuke; Matsumoto, Tomoyuki; Ueha, Takeshi; Uefuji, Atsuo; Inokuchi, Takao; Takayama, Koji; Hashimoto, Shingo; Hayashi, Shinya; Matsushita, Takehiko; Kuroda, Ryosuke

doi:10.1177/0363546518755753

Cited by 17 publications

(22 citation statements)

References 31 publications

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“…Consistent with the finding, Nakano et al (16) confirmed that ACL-derived vascular cells harvested from adolescents were superior to those of adults over 30-year-old in their capacity enhancing tendon- (21). Furthermore, Kirizuki et al reported that the nonreattachment remnants, compared with the reattachment remnants, have more CD34-positive cells in ACL ruptured tissues and exhibited higher potential for proliferation and multilineage differentiation, especially in osteogenic and endotheliogenic differentiation (22). Considering these findings, when surgeons perform remnant preserving ACLR or ACLR with ruptured tissue, the patient's age, time taken from ACL injury to surgery, and remnant types should also be considered when predicting healing ability.…”

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confidence: 67%

Therapeutic potential of vascular stem cells for anterior cruciate ligament reconstruction

et al. 2019

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confidence: 67%

Therapeutic potential of vascular stem cells for anterior cruciate ligament reconstruction

et al. 2019

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“…The results showed that preservation without remnant tensioning had significant advantages in terms of Lysholm score, IKDC grade, Pivot-shift test and side-to-side difference, but group preservation with remnant tensioning does not show the significant superiority, comparing to Group ACLR-S. The results may be due to the points mentioned above, the differences in ACLR procedures, remnant placement, and amount and quality of remnant preservation ( 33 , 40 , 48 , 49 ).…”

Section: Discussionmentioning

confidence: 94%

“…After ACL injury, mechanoreceptors and conduction pathways are injured, resulting in affected neuromuscular reflexes and ultimately, and affecting knee proprioception and stability ( 38 ). Studies have shown that after ACL injury, proprioceptors still exist at ACL remnant, which are involved in completing part of the proprioceptive function, and the number of receptors is positively correlated with the proprioceptive level of the knee joint ( 39 , 40 ). Animal experiments showed that the number and density of proprioceptors were significantly higher after ACLR-R, comparing to standard ACLR ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of remnant preservation in anterior cruciate ligament reconstruction: A systematic review and meta-analysis

Xie

Zhong

et al. 2022

Front. Surg.

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BackgroundCompared with standard anterior cruciate ligament (ACL) reconstruction, it is controversial whether anterior cruciate ligament reconstruction (ACLR) with remnant preservation can lead to better clinical outcomes. We conducted a systematic study and meta-analysis to assess the differences in clinical efficacy between the two.MethodWe searched for clinical randomized controlled studies and cohort studies included in the Cochrane library, PubMed, and Embase from March 2012 to March 2022 in English. The included studies were ACLR with or without remant preservation, and the data were extracted and the quality of the included studies was assessed by two authors, respectively. Revman 5.4 was used for statistical analysis and conclusions were presented.ResultTen articles containing a total of 777 patients were finally included. There was no significant difference in postoperative Lachman test [OR = 1.66, 95%CI (0.79, 3.49), P = 0.18 > 0.05], Tegner score [SMD = −0.13, 95%CI (−0.47, 0.22), P = 0.46 > 0.05], synovial coverage rate by second-look arthroscopy [OR = 1.55, 95%CI (0.66, 3.65), P = 0.32 > 0.05], the rate of cyclops lesion [OR = 3.92, 95%CI (0.53, 29.29), P = 0.18 > 0.05], joint range of motion [SMD = 0.27, 95%CI (−0.13, 0.68), P = 0.19 > 0.05] and re-injury rate [OR = 0.57, 95%CI (0.18, 1.74), P = 0.32 > 0.05] between the two groups. There were statistically significant differences in postoperative Lysholm score [SMD = 0.98, 95% CI (0.32, 1.64), P = 0.004 < 0.05], International Knee Documantation Committee grade (IKDC grade) [OR = 2.19, 95%CI (1.03, 4.65), P = 0.04 < 0.05], Pivot shift test [OR = 1.71, 95%CI (1.06, 2.77), P = 0.03 < 0.05], KT1000/2000 arthrometer side-to-side difference [SMD = −0.22, 95%CI (−0.42, −0.03), P = 0.02 < 0.05], operation time [SMD = 11.69, 95%CI (8.85, 14.54), P = 0.00001 < 0.05] and degree of tibial tunnel enlargement [SMD = −0.66, 95%CI (−1.08, −0.23), P = 0.002 < 0.05].ConclusionThis meta-analysis concluded that remnant preservation significantly had better results in terms of patient functional score (Lysholm, IKDC), knee stability (Pivot shift test, postoperative side-to-side anterior laxity) and tibial tunnel enlargement. In terms of complications (incidence of Cyclops lesions, range of motion, re-injury rate), no significant differences were seen between the two groups. Although many studies concluded that remnant preservation could bring better synovial coverage, this meta-analysis indicated that there is insufficient evidence to support it, possibly due to different remnant preservation procedures.The potential risks associated with longer operation times are also worth considering.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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. Furthermore, Kirizuki et al 33 studied ACL healing potential by morphologic pattern (attachment of the remnants to surrounding tissues) and found a significantly higher number of CD34 + cells in the non-reattachment group as compared to the reattachment group.…”

Section: Discussionmentioning

confidence: 99%

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

Lee

et al. 2020

Sci Rep

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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...

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The Influence of Ruptured Scar Pattern on the Healing Potential of Anterior Cruciate Ligament Remnant Cells

Abstract: If healing potential differs among the morphologic patterns of ACL remnants, surgeons may expect the healing potential when preserving remnants.

Cited by 17 publications

References 31 publications

Therapeutic potential of vascular stem cells for anterior cruciate ligament reconstruction

Therapeutic potential of vascular stem cells for anterior cruciate ligament reconstruction

Effects of remnant preservation in anterior cruciate ligament reconstruction: A systematic review and meta-analysis

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

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