Isolation and Characterization of Human Anterior Cruciate Ligament-Derived Vascular Stem Cells

Abstract

The anterior cruciate ligament (ACL) usually fails to heal after rupture mainly due to the inability of the cells within the ACL tissue to establish an adequate healing process, making graft reconstruction surgery a necessity. However, some reports have shown that there is a healing potential of ACL with primary suture repair. Although some reports showed the existence of mesenchymal stem cell-like cells in human ACL tissues, their origin still remains unclear. Recently, blood vessels have been reported to represent a rich supply of stem/ progenitor cells with a characteristic expression of CD34 and CD146. In this study, we attempted to validate the hypothesis that CD34-and CD146-expressing vascular cells exist in hACL tissues, have a potential for multilineage differentiation, and are recruited to the rupture site to participate in the intrinsic healing of injured ACL. Immunohistochemistry and flow cytometry analysis of hACL tissues demonstrated that it contains significantly more CD34 and CD146-positive cells in the ACL ruptured site compared with the noninjured midsubstance. CD34 + CD45 -cells isolated from ACL ruptured site showed higher expansionary potentials than CD146 + CD45 -and CD34 -CD146 -CD45 -cells, and displayed higher differentiation potentials into osteogenic, adipogenic, and angiogenic lineages than the other cell populations. Immunohistochemistry of fetal and adult hACL tissues demonstrated a higher number of CD34 and CD146-positive cells in the ACL septum region compared with the midsubstance. In conclusion, our findings suggest that the ACL septum region contains a population of vascular-derived stem cells that may contribute to ligament regeneration and repair at the site of rupture.

Post injury changes in the properties of mesenchymal stem cells derived from human anterior cruciate ligaments

“…Increased CD34 positivity might reflect increases in other cells, such as hematopoietic and vascular endothelial cells. Matsumoto et al reported a higher number of CD34 and CD146-positive cells in the ACL septum region compared with the midsubstance and a population of vascular-derived stem cells in the ACL septum region [29]. Their findings might support our results.…”

Harnessing endogenous stem/progenitor cells for tendon regeneration

“…The primary function of tenocytes is to maintain tissue homeostasis (33,34). Recently, a rare population of cells in tendons was identified to possess stem/ progenitor cell properties (35,36). The rarity of stem/progenitor cells in tendons can be appreciated in that they likely account for <1% of all cells, which together represent only 5% of total tissue volume.…”

Single-Bundle Augmentation for a Partial Tear of the Anterior Cruciate Ligament

“…Additionally, animal models have shown that the synovial sheath and septum around the ACL contain vascularderived stem cells that may contribute to ACL regeneration and repair. 19,20 ACL Augmentation has been shown to have higher biomechanical strength, decreased graft rupture rates, and better postoperative anterior stability than traditional reconstruction. 20 This technique is not without its risks, however.…”