New Strategies for Anterior Cruciate Ligament Partial Rupture Using Bone Marrow Transplantation in Rats

Abstract

The purpose of this study was to compare anterior cruciate ligament (ACL) regeneration between animal groups subjected to intra-articular injection of fresh whole bone marrow cells (BMCs), cultured mesenchymal stem cells (MSCs), or saline. Partially transected ACLs in Fischer 344/Nslc rats were prepared, followed by injection of BMCs, MSCs, or saline into the articular cavity at 1 week after transection. Donor cells expressing green fluorescent protein were detected in the recipient's transected ACLs at 4 weeks in the BMC and MSC groups, and their ACLs appeared almost normal histologically. Further, there were significantly more mature spindle cells in the BMC group than in the saline group at 4 weeks. Biomechanically, the tensile strength in the BMC group reached near normal levels at 4 weeks after injection. The levels of transforming growth factor-β1 in the ACL tissue and knee joint fluid in the BMC group were increased significantly compared with that of the saline group at 4 weeks as detected by immunohistochemical analysis. In conclusion, intra-articular bone marrow transplantation using fresh whole BMCs is an effective treatment for ACL partial rupture. This therapy is easy to apply in a clinical setting because no culture system is required for collecting MSCs.

Validation of Porcine Knee as a Sex-specific Model to Study Human Anterior Cruciate Ligament Disorders

“…Animal models have been long used to study ACL injuries, treatments, and associated complications [6,7,17,19,20,22,26,44,45]. Animal models provide researchers with the ability to perform invasive procedures and to obtain samples at specific times that are not possible in human trials.…”

Engraftment of autologous bone marrow cells into the injured cranial cruciate ligament in dogs

“…This study evaluated engraftment of fluorescent-labelled BMCs into injured ligaments when applied into the articular cavity in dogs with spontaneous CCL injury. The decision to use BMCs instead of MSCs was based on ease of processing, making the procedure practical for future use in a clinical setting, as well as the potential additional benefit of BMCs based on studies in a rat model (Oe et al, 2011).…”

“…Differentiation between graft and host cells after transplantation requires a method that labels cells of interest and identifies them after harvesting at a later time. Previous studies used BMCs or MSCs expressing green fluorescent protein (GFP) injected into the injured stifle joints of dogs (Mokbel et al, 2011a), donkeys (Mokbel et al, 2011b) and goats (Murphy et al, 2003), as well as GFP transgenic animals (Oe et al, 2011). An advantage of using GFP is its potential use in long-term studies as daughter cells adopt GFP gene expression and, with it, fluorescence is multiplied after several cell divisions.…”

“…Bone marrow-derived MSCs hold particular promise for tissue repair because of their ability to engraft into tissues and differentiate into the target tissue cell type, including fibroblasts, osteocytes, adipocytes, chondrocytes and myocytes (Pittenger et al, 1999;Chamberlain et al, 2007). In recent studies, MSCs were found to accelerate healing of transected ligaments in animal models (Agung et al, 2006;Kanaya et al, 2007;Kim et al, 2011) and evidence suggests that fresh whole bone marrow cells (BMCs) may have superior effects compared to purified MSCs, presumably because of an additional benefit of haematopoietic stem cells (Oe et al, 2011). Indeed, injured rat ACLs treated with BMCs had more mature fibroblasts and tighter collagen bundles compared to those treated with MSCs, leading the authors to conclude that bone marrow (BM) transplantation is an effective treatment for ACL injury (Oe et al, 2011).…”

“…In recent studies, MSCs were found to accelerate healing of transected ligaments in animal models (Agung et al, 2006;Kanaya et al, 2007;Kim et al, 2011) and evidence suggests that fresh whole bone marrow cells (BMCs) may have superior effects compared to purified MSCs, presumably because of an additional benefit of haematopoietic stem cells (Oe et al, 2011). Indeed, injured rat ACLs treated with BMCs had more mature fibroblasts and tighter collagen bundles compared to those treated with MSCs, leading the authors to conclude that bone marrow (BM) transplantation is an effective treatment for ACL injury (Oe et al, 2011). To date, no studies have investigated the potential benefit of stem cell adjunctive treatment in dogs with experimental or spontaneous CCL injury.…”