Application of Stem Cell Therapy for ACL Graft Regeneration

Abstract

Graft regeneration after anterior cruciate ligament (ACL) reconstruction surgery is a complex three-stage process, which usually takes a long duration and often results in fibrous scar tissue formation that exerts a detrimental impact on the patients’ prognosis. Hence, as a regeneration technique, stem cell transplantation has attracted increasing attention. Several different stem cell types have been utilized in animal experiments, and almost all of these have shown good capacity in improving tendon-bone regeneration. Various differentiation inducers have been widely applied together with stem cells to enhance specific lineage differentiation, such as recombinant gene transfection, growth factors, and biomaterials. Among the various different types of stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) have been investigated the most, while ligament stem progenitor cells (LDSCs) have demonstrated the best potential in generating tendon/ligament lineage cells. In the clinic, 4 relevant completed trials have been reported, but only one trial with BMSCs showed improved outcomes, while 5 relevant trials are still in progress. This review describes the process of ACL graft regeneration after implantation and summarizes the current application of stem cells from bench to bedside, as well as discusses future perspectives in this field.

Advances in Regenerative Sports Medicine Research

“…Knee ligament injuries often result in ligament deficiency and joint instability and necessitate ligament reconstruction (Pike, et al, 2019). To prevent the donor site morbidity that can occur with autografts, the high failure rate with allografts, and the nongraft-bone healing associated with non-receiver transformable synthetic ligaments, receiver transformable regenerative ligaments are considered an alternative choice (Wang C. et al, 2021). Chronic Achilles' tendon rupture often results in tendon defects that make the direct opposition of the separated tendon ends impossible and graft bridging a necessary choice; consequently, there is demand for regenerative or receiver transformable artificial Achilles' tendons (Arshad, et al, 2021).…”

Biologic Acl Repair Augmentation

“…Wang et al concluded that many stem cell lines had good capacity to promote tendon-bone regeneration in animal models. 54 When considering the various types of stem cells, ligament-derived stem cells (LDSC) showed better potential for lineagespecific tendon/ligament differentiation. 55 Stem cells have a better capacity to differentiate into ligament, fibrocartilage, and bone, promoting graft regeneration, especially when they are used with differentiation inducers, such as growth factors, mechanical, and biomaterial stimuli.…”

Current trends in the anterior cruciate ligament part 1: biology and biomechanics

“…Translation of early biologics studies to the clinical setting is still limited. For example, a recently published study outlining stem cell research in management of ACL injury demonstrated only four completed clinical trials and nine ongoing trials [148]. Among these, one double-blind RCT demonstrated the safety of intra-articular stem cell injection following ACL reconstruction with potential improvements in terms of reported pain and symptoms [150].…”